Blinatumomab in Treating Younger Patients With Relapsed B-cell Acute Lymphoblastic Leukemia

NCT02101853 | Active Not Recruiting Phase 3 Results

• 6 other identifiers: NCI-2014-00631s15-00970COG-AALL1331AALL1331U10CA098543U10CA180886
• Study Type: interventional
• Target: 669
• Locations: 5 countries
• Sites: 186

Brief Summary

This randomized phase III trial studies how well blinatumomab works compared with standard combination chemotherapy in treating patients with B-cell acute lymphoblastic leukemia that has returned after a period of improvement (relapsed). Immunotherapy with blinatumomab may allow the body's immune system to attack and destroy some types of leukemia cells. It is not yet known whether blinatumomab is more effective than standard combination chemotherapy in treating relapsed B-cell acute lymphoblastic leukemia.

Conditions

Recurrent B Acute Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (2)

• Disease Free Survival (DFS) of High-risk (HR) and Intermediate-risk (IR) Relapse Patients

  DFS rates of HR and IR relapse B-ALL patients who are randomized following Induction Block 1 chemotherapy to receive either two intensive chemotherapy blocks or two 5-week blocks of blinatumomab (HR/IR Randomization). DFS is calculated as the time from randomization to date of first event (treatment failure, relapse, second malignancy, remission death) or date of last contact. Two-year DFS estimates will be calculated from date of randomization for both Arm A and Arm B. Two-sided 95% confidence intervals will be calculated.

  Up to 2 years from date of randomization

• Disease Free Survival (DFS) of Low Risk (LR) Relapse Patients

  DFS rates of LR relapse B-ALL patients who are randomized following Block 1 chemotherapy to receive either chemotherapy alone or chemotherapy plus blinatumomab (LR Randomization). DFS is calculated as the time from randomization to date of first event (relapse, second malignancy, remission death) or date of last contact. Three-year DFS estimates will be calculated from date of randomization for both Arm C and Arm D. Two-sided 95% confidence intervals will be calculated.

  Up to 3 years from date of randomization

Secondary Outcomes (2)

• Overall Survival (OS) of HR and IR Relapse Patients

  Up to 2 years from date of randomization

• Overall Survival (OS) of LR Relapse Patients

  Up to 3 years from date of randomization

Other Outcomes (7)

• Rates of Minimal Residual Disease (MRD) Positivity (> 0.01%)

  Up to 12 weeks

• Hematologic Complete Remission Rate (for Treatment Failure Patients Not Previously Receiving Blinatumomab)

  Up to 12 weeks

• MRD Negativity (< 0.01%) Rate (for Treatment Failure Patients Not Previously Receiving Blinatumomab)

  Up to 12 weeks

Study Arms (4)

Arm A (HR and IR control)

ACTIVE COMPARATOR

Patients receive Block 2 over 4 weeks, Block 3 over 4 weeks, and then undergo allogeneic HSCT. Closed effective September 18, 2019.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Asparaginase; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Dexamethasone; Drug: Etoposide; Drug: Leucovorin Calcium; Drug: Methotrexate; Drug: Mitoxantrone; Drug: Mitoxantrone Hydrochloride; Drug: Pegaspargase; Other: Pharmacological Study; Drug: Therapeutic Hydrocortisone; Drug: Vincristine; Drug: Vincristine Sulfate

Arm B (HR and IR blinatumomab)

EXPERIMENTAL

Patients receive Blinatumomab Block 1 over 5 weeks, Blinatumomab Block 2 over 5 weeks, and then undergo allogeneic HSCT.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Biological: Blinatumomab; Drug: Cytarabine; Drug: Dexamethasone; Drug: Methotrexate; Other: Pharmacological Study; Drug: Therapeutic Hydrocortisone

Arm C (LR control)

ACTIVE COMPARATOR

Patients receive Block 2 over 4 weeks, Block 3 over 4 weeks, Continuation 1 over 8 weeks, Continuation 2 over 8 weeks, and then Maintenance.

Drug: Asparaginase; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Dexamethasone; Drug: Etoposide; Drug: Leucovorin Calcium; Drug: Mercaptopurine; Drug: Methotrexate; Drug: Pegaspargase; Other: Pharmacological Study; Radiation: Radiation Therapy; Drug: Therapeutic Hydrocortisone; Drug: Thioguanine; Drug: Vincristine; Drug: Vincristine Sulfate

Arm D (LR blinatumomab)

EXPERIMENTAL

Patients receive Block 2 over 4 weeks, Blinatumomab Cycle 1 over 5 weeks, Continuation 1 over 8 weeks, Blinatumomab Cycle 2 over 5 weeks, Continuation 2 over 8 weeks, Blinatumomab Cycle 3 over 5 weeks, and then Maintenance.

Biological: Blinatumomab; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Dexamethasone; Drug: Etoposide; Drug: Leucovorin Calcium; Drug: Mercaptopurine; Drug: Methotrexate; Drug: Pegaspargase; Other: Pharmacological Study; Radiation: Radiation Therapy; Drug: Therapeutic Hydrocortisone; Drug: Thioguanine; Drug: Vincristine; Drug: Vincristine Sulfate

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo allogeneic HSCT

Also known as: Allogeneic, Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT, Stem Cell Transplantation, Allogeneic

Arm A (HR and IR control); Arm B (HR and IR blinatumomab)

Asparaginase DRUG

Given IM or IV

Also known as: ASP-1, Asparaginase II, Asparaginase-E.Coli, Colaspase, Elspar, Kidrolase, L-Asnase, L-ASP, L-Asparaginase, L-Asparagine Amidohydrolase, Laspar, Lcf-ASP, Leucogen, Leunase, MK-965, Paronal, Re-82-TAD-15, Serasa, Spectrila

Arm A (HR and IR control); Arm C (LR control)

Blinatumomab BIOLOGICAL

Given IV

Also known as: AMG 103, AMG-103, AMG103, Anti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody, Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103, Blincyto, MEDI 538, MEDI-538, MEDI538, MT 103, MT-103, MT103

Arm B (HR and IR blinatumomab); Arm D (LR blinatumomab)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518, B-518, B518, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR 138719, WR- 138719, WR-138719, WR138719

Arm A (HR and IR control); Arm C (LR control); Arm D (LR blinatumomab)

Cytarabine DRUG

Given IT and IV or SC

Also known as: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-Cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453

Arm A (HR and IR control); Arm B (HR and IR blinatumomab); Arm C (LR control); Arm D (LR blinatumomab)

Dexamethasone DRUG

Given PO or IV

Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycadron, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decadron DP, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasone Intensol, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Dxevo, Fluorodelta, Fortecortin, Gammacorten, Hemady, Hexadecadrol, Hexadrol, LenaDex, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex

Arm A (HR and IR control); Arm B (HR and IR blinatumomab); Arm C (LR control); Arm D (LR blinatumomab)

Etoposide DRUG

Given IV

Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP 16213, VP-16, VP-16-213, VP-16213, VP16, VP16213

Arm A (HR and IR control); Arm C (LR control); Arm D (LR blinatumomab)

Leucovorin Calcium DRUG

Given IV or PO

Also known as: Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate, Calcium Leucovorin, Calfolex, Calinat, Cehafolin, Citofolin, Citrec, Citrovorum Factor, Cromatonbic Folinico, Dalisol, Disintox, Divical, Ecofol, Emovis, Factor, Citrovorum, Flynoken A, Folaren, Folaxin, FOLI-cell, Foliben, Folidan, Folidar, Folinac, Folinate Calcium, folinic acid, Folinic Acid Calcium Salt Pentahydrate, Folinoral, Folinvit, Foliplus, Folix, Imo, Lederfolat, Lederfolin, Leucosar, leucovorin, Rescufolin, Rescuvolin, Tonofolin, Wellcovorin

Arm A (HR and IR control); Arm C (LR control); Arm D (LR blinatumomab)

Mercaptopurine DRUG

Given PO

Also known as: 3H-Purine-6-thiol, 6 MP, 6 Thiohypoxanthine, 6 Thiopurine, 6-Mercaptopurine, 6-Mercaptopurine Monohydrate, 6-MP, 6-Purinethiol, 6-Thiopurine, 6-Thioxopurine, 6H-Purine-6-thione, 1,7-dihydro- (9CI), 7-Mercapto-1,3,4,6-tetrazaindene, Alti-Mercaptopurine, Azathiopurine, Bw 57-323H, Flocofil, Ismipur, Leukerin, Leupurin, Mercaleukim, Mercaleukin, Mercaptina, Mercaptopurinum, Mercapurin, Mern, NCI-C04886, Puri-Nethol, Purimethol, Purine, 6-mercapto-, Purine-6-thiol (8CI), Purine-6-thiol, monohydrate, Purinethiol, Purinethol, U-4748, WR-2785

Arm C (LR control); Arm D (LR blinatumomab)

Methotrexate DRUG

Given IT, IV, and PO

Also known as: Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate, CL 14377, CL-14377, Emtexate, Emthexat, Emthexate, Farmitrexat, Fauldexato, Folex, Folex PFS, Jylamvo, Lantarel, Ledertrexate, Lumexon, Maxtrex, Medsatrexate, Metex, Methoblastin, Methotrexate LPF, Methotrexate Methylaminopterin, Methotrexatum, Metotrexato, Metrotex, Mexate, Mexate-AQ, MTX, Novatrex, Rheumatrex, Texate, Tremetex, Trexeron, Trixilem, WR-19039

Arm A (HR and IR control); Arm B (HR and IR blinatumomab); Arm C (LR control); Arm D (LR blinatumomab)

Mitoxantrone DRUG

Given IV

Also known as: Dihydroxyanthracenedione, Mitozantrone

Arm A (HR and IR control)

Mitoxantrone Hydrochloride DRUG

Given IV

Also known as: CL 232315, DHAD, DHAQ, Dihydroxyanthracenedione Dihydrochloride, Mitoxantrone Dihydrochloride, Mitoxantroni Hydrochloridum, Mitozantrone Hydrochloride, Mitroxone, Neotalem, Novantrone, Onkotrone, Pralifan

Arm A (HR and IR control)

Pegaspargase DRUG

Given IV

Also known as: L-Asparaginase with Polyethylene Glycol, Oncaspar, Oncaspar-IV, PEG-Asparaginase, PEG-L-Asparaginase, PEG-L-Asparaginase (Enzon - Kyowa Hakko), PEGLA, Polyethylene Glycol L-Asparaginase, Polyethylene Glycol-L-Asparaginase

Arm A (HR and IR control); Arm C (LR control); Arm D (LR blinatumomab)

Pharmacological Study OTHER

Correlative studies

Arm A (HR and IR control); Arm B (HR and IR blinatumomab); Arm C (LR control); Arm D (LR blinatumomab)

Radiation Therapy RADIATION

Undergo cranial radiation therapy

Also known as: Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Arm C (LR control); Arm D (LR blinatumomab)

Therapeutic Hydrocortisone DRUG

Given IT

Also known as: Aeroseb-HC, Barseb HC, Barseb-HC, Cetacort, Cort-Dome, Cortef, Cortenema, Cortifan, Cortisol, Cortispray, Cortril, Dermacort, Domolene, Eldecort, Hautosone, Heb-Cort, Hydrocortisone, Hydrocortone, Hytone, Komed-HC, Nutracort, Proctocort, Rectoid

Arm A (HR and IR control); Arm B (HR and IR blinatumomab); Arm C (LR control); Arm D (LR blinatumomab)

Thioguanine DRUG

Given PO

Also known as: 2-Amino 6MP, 2-Amino-1,7-dihydro-6H-purine-6-thione, 2-Amino-6-mercaptopurine, 2-Amino-6-purinethiol, 2-Aminopurin-6-thiol, 2-Aminopurine-6(1H)-thione, 2-Aminopurine-6-thiol, 2-Aminopurine-6-thiol Hemihydrate, 2-Mercapto-6-aminopurine, 6-Amino-2-mercaptopurine, 6-Mercapto-2-aminopurine, 6-Mercaptoguanine, 6-TG, 6H-Purine-6-thione, 2-amino-1,7-dihydro- (9CI), BW 5071, Lanvis, Tabloid, Thioguanine Hemihydrate, Thioguanine Hydrate, Tioguanin, Tioguanine, Wellcome U3B, WR-1141, X 27

Arm C (LR control); Arm D (LR blinatumomab)

Vincristine DRUG

Given IV

Also known as: LCR, Leurocristine, VCR, Vincrystine

Arm A (HR and IR control); Arm C (LR control); Arm D (LR blinatumomab)

Vincristine Sulfate DRUG

Given IV

Also known as: Kyocristine, Leurocristine Sulfate, Leurocristine, sulfate, Oncovin, Vincasar, Vincosid, Vincrex, Vincristine, sulfate

Arm A (HR and IR control); Arm C (LR control); Arm D (LR blinatumomab)

Eligibility Criteria

• Age: 1 Year - 31 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients \>= 1 year and \< 31 years of age at the time of relapse will be eligible
• First relapse of B-ALL, allowable sites of disease include isolated bone marrow, combined bone marrow and CNS and/or testicular, and isolated CNS and/or testicular; extramedullary sites are limited to the CNS and testicles
• No waiting period for patients who relapse while receiving standard maintenance therapy
• Patients who relapse on frontline therapy in phases other than maintenance must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
• Cytotoxic therapy: at least 14 days since the completion of cytotoxic therapy with the exception of hydroxyurea, which is permitted up to 24 hours prior to the start of protocol therapy, or maintenance chemotherapy, or intrathecal chemotherapy (methotrexate strongly preferred) administered at the time of the required diagnostic lumbar puncture to establish baseline CNS status
• Biologic (anti-neoplastic) agent: at least 7 days since the completion of therapy with a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
• Stem cell transplant or rescue: patient has not had a prior stem cell transplant or rescue
• Patient has not had prior treatment with blinatumomab
• With the exception of intrathecal chemotherapy (methotrexate strongly preferred; cytarabine is permissible) administered at the time of the required diagnostic lumbar puncture to establish baseline CNS status, patient has not received prior relapse-directed therapy (i.e., this protocol is intended as the INITIAL treatment of first relapse)
• Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2; use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 or a serum creatinine based on age/gender as follows:
• to \< 2 years: =\< 0.6 mg/dL
• to \< 6 years: =\< 0.8 mg/dL
• to \< 10 years: =\< 1 mg/dL
• to \< 13 years: =\< 1.2 mg/dL

You may not qualify if:

• Patients with Philadelphia chromosome positive/breakpoint cluster region protein (BCR)-Abelson murine leukemia viral oncogene homolog 1 (ABL1)+ ALL are not eligible
• Patients with Burkitt leukemia/lymphoma or mature B-cell leukemia are not eligible
• Patients with T-lymphoblastic leukemia (T-ALL)/lymphoblastic lymphoma (T-LL) are not eligible
• Patients with B-lymphoblastic lymphoma (B-LL) are not eligible
• Patients with known optic nerve and/or retinal involvement are not eligible; patients who are presenting with visual disturbances should have an ophthalmologic exam and, if indicated, a magnetic resonance imaging (MRI) to determine optic nerve or retinal involvement
• Patients known to have one of the following concomitant genetic syndromes: Down syndrome, Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome
• Patients with known human immunodeficiency virus (HIV) infection
• Patients with known allergy to mitoxantrone, cytarabine, or both etoposide and etoposide phosphate (Etopophos)
• Lactating females who plan to breastfeed
• Patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs; a pregnancy test is required for female patients of childbearing potential
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
• Patients with pre-existing significant central nervous system pathology that would preclude treatment with blinatumomab, including: history of severe brain injury, dementia, cerebellar disease, organic brain syndrome, psychosis, coordination/movement disorder, or autoimmune disease with CNS involvement are not eligible; patients with a history of cerebrovascular ischemia/hemorrhage with residual deficits are not eligible; (patients with a history of cerebrovascular ischemia/hemorrhage remain eligible provided all neurologic deficits have resolved)
• Patients with uncontrolled seizure disorder are not eligible; (patients with seizure disorders that do not require antiepileptic drugs, or are well controlled with stable doses of antiepileptic drugs remain eligible)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (186)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

Location

USA Health Strada Patient Care Center

Mobile, Alabama, 36604, United States

Location

Providence Alaska Medical Center

Anchorage, Alaska, 99508, United States

Location

Banner Children's at Desert

Mesa, Arizona, 85202, United States

Location

Phoenix Childrens Hospital

Phoenix, Arizona, 85016, United States

Location

Banner University Medical Center - Tucson

Tucson, Arizona, 85719, United States

Location

Arkansas Children's Hospital

Little Rock, Arkansas, 72202-3591, United States

Location

Kaiser Permanente Downey Medical Center

Downey, California, 90242, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Loma Linda University Medical Center

Loma Linda, California, 92354, United States

Location

Miller Children's and Women's Hospital Long Beach

Long Beach, California, 90806, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Mattel Children's Hospital UCLA

Los Angeles, California, 90095, United States

Location

Valley Children's Hospital

Madera, California, 93636, United States

Location

UCSF Benioff Children's Hospital Oakland

Oakland, California, 94609, United States

Location

Kaiser Permanente-Oakland

Oakland, California, 94611, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, 94304, United States

Location

Sutter Medical Center Sacramento

Sacramento, California, 95816, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

Rady Children's Hospital - San Diego

San Diego, California, 92123, United States

Location

UCSF Medical Center-Mission Bay

San Francisco, California, 94158, United States

Location

Santa Barbara Cottage Hospital

Santa Barbara, California, 93102, United States

Location

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Torrance, California, 90502, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center

Denver, Colorado, 80218, United States

Location

Connecticut Children's Medical Center

Hartford, Connecticut, 06106, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Alfred I duPont Hospital for Children

Wilmington, Delaware, 19803, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Broward Health Medical Center

Fort Lauderdale, Florida, 33316, United States

Location

Golisano Children's Hospital of Southwest Florida

Fort Myers, Florida, 33908, United States

Location

UF Health Cancer Institute - Gainesville

Gainesville, Florida, 32610, United States

Location

Memorial Regional Hospital/Joe DiMaggio Children's Hospital

Hollywood, Florida, 33021, United States

Location

Nemours Children's Clinic-Jacksonville

Jacksonville, Florida, 32207, United States

Location

Palms West Radiation Therapy

Loxahatchee Groves, Florida, 33470, United States

Location

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States

Location

AdventHealth Orlando

Orlando, Florida, 32803, United States

Location

Arnold Palmer Hospital for Children

Orlando, Florida, 32806, United States

Location

Nemours Children's Clinic - Pensacola

Pensacola, Florida, 32504, United States

Location

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

Tampa General Hospital

Tampa, Florida, 33606, United States

Location

Saint Joseph's Hospital/Children's Hospital-Tampa

Tampa, Florida, 33607, United States

Location

Saint Mary's Medical Center

West Palm Beach, Florida, 33407, United States

Location

Children's Healthcare of Atlanta - Arthur M Blank Hospital

Atlanta, Georgia, 30329, United States

Location

Memorial Health University Medical Center

Savannah, Georgia, 31404, United States

Location

Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, 96826, United States

Location

Saint Luke's Cancer Institute - Boise

Boise, Idaho, 83712, United States

Location

Lurie Children's Hospital-Chicago

Chicago, Illinois, 60611, United States

Location

University of Illinois

Chicago, Illinois, 60612, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Advocate Children's Hospital-Oak Lawn

Oak Lawn, Illinois, 60453, United States

Location

Advocate Children's Hospital-Park Ridge

Park Ridge, Illinois, 60068, United States

Location

Saint Jude Midwest Affiliate

Peoria, Illinois, 61637, United States

Location

Southern Illinois University School of Medicine

Springfield, Illinois, 62702, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Ascension Saint Vincent Indianapolis Hospital

Indianapolis, Indiana, 46260, United States

Location

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

Norton Children's Hospital

Louisville, Kentucky, 40202, United States

Location

Ochsner Medical Center Jefferson

New Orleans, Louisiana, 70121, United States

Location

Eastern Maine Medical Center

Bangor, Maine, 04401, United States

Location

Maine Children's Cancer Program

Scarborough, Maine, 04074, United States

Location

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Sinai Hospital of Baltimore

Baltimore, Maryland, 21215, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Walter Reed National Military Medical Center

Bethesda, Maryland, 20889-5600, United States

Location

Tufts Children's Hospital

Boston, Massachusetts, 02111, United States

Location

Baystate Medical Center

Springfield, Massachusetts, 01199, United States

Location

UMass Memorial Medical Center - University Campus

Worcester, Massachusetts, 01655, United States

Location

C S Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Henry Ford Health Saint John Hospital

Detroit, Michigan, 48236, United States

Location

Michigan State University

East Lansing, Michigan, 48823, United States

Location

Hurley Medical Center

Flint, Michigan, 48503, United States

Location

Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital

Grand Rapids, Michigan, 49503, United States

Location

Corewell Health Children's

Royal Oak, Michigan, 48073, United States

Location

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, 55404, United States

Location

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, 64108, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Mercy Hospital Saint Louis

St Louis, Missouri, 63141, United States

Location

Children's Hospital and Medical Center of Omaha

Omaha, Nebraska, 68114, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Sunrise Hospital and Medical Center

Las Vegas, Nevada, 89109, United States

Location

Alliance for Childhood Diseases/Cure 4 the Kids Foundation

Las Vegas, Nevada, 89135, United States

Location

Summerlin Hospital Medical Center

Las Vegas, Nevada, 89144, United States

Location

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

Lebanon, New Hampshire, 03756, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Morristown Medical Center

Morristown, New Jersey, 07960, United States

Location

Saint Peter's University Hospital

New Brunswick, New Jersey, 08901, United States

Location

Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital

New Brunswick, New Jersey, 08903, United States

Location

Newark Beth Israel Medical Center

Newark, New Jersey, 07112, United States

Location

Saint Joseph's Regional Medical Center

Paterson, New Jersey, 07503, United States

Location

Albany Medical Center

Albany, New York, 12208, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

NYU Langone Hospital - Long Island

Mineola, New York, 11501, United States

Location

The Steven and Alexandra Cohen Children's Medical Center of New York

New Hyde Park, New York, 11040, United States

Location

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, 10016, United States

Location

Mount Sinai Hospital

New York, New York, 10029, United States

Location

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

Location

NYP/Weill Cornell Medical Center

New York, New York, 10065, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Stony Brook University Medical Center

Stony Brook, New York, 11794, United States

Location

State University of New York Upstate Medical University

Syracuse, New York, 13210, United States

Location

Montefiore Medical Center - Moses Campus

The Bronx, New York, 10467, United States

Location

New York Medical College

Valhalla, New York, 10595, United States

Location

Mission Hospital

Asheville, North Carolina, 28801, United States

Location

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, 28203, United States

Location

Novant Health Presbyterian Medical Center

Charlotte, North Carolina, 28204, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

East Carolina University

Greenville, North Carolina, 27834, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Children's Hospital Medical Center of Akron

Akron, Ohio, 44308, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Rainbow Babies and Childrens Hospital

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Dayton Children's Hospital

Dayton, Ohio, 45404, United States

Location

ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital

Toledo, Ohio, 43606, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Legacy Emanuel Children's Hospital

Portland, Oregon, 97227, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Lehigh Valley Hospital-Cedar Crest

Allentown, Pennsylvania, 18103, United States

Location

Lehigh Valley Hospital - Muhlenberg

Bethlehem, Pennsylvania, 18017, United States

Location

Geisinger Medical Center

Danville, Pennsylvania, 17822, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Saint Christopher's Hospital for Children

Philadelphia, Pennsylvania, 19134, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

BI-LO Charities Children's Cancer Center

Greenville, South Carolina, 29605, United States

Location

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota, 57117-5134, United States

Location

T C Thompson Children's Hospital

Chattanooga, Tennessee, 37403, United States

Location

East Tennessee Childrens Hospital

Knoxville, Tennessee, 37916, United States

Location

The Children's Hospital at TriStar Centennial

Nashville, Tennessee, 37203, United States

Location

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Dell Children's Medical Center of Central Texas

Austin, Texas, 78723, United States

Location

Driscoll Children's Hospital

Corpus Christi, Texas, 78411, United States

Location

Medical City Dallas Hospital

Dallas, Texas, 75230, United States

Location

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390, United States

Location

El Paso Children's Hospital

El Paso, Texas, 79905, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, 77030, United States

Location

Covenant Children's Hospital

Lubbock, Texas, 79410, United States

Location

Children's Hospital of San Antonio

San Antonio, Texas, 78207, United States

Location

Methodist Children's Hospital of South Texas

San Antonio, Texas, 78229, United States

Location

Scott and White Memorial Hospital

Temple, Texas, 76508, United States

Location

Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

Location

Inova Fairfax Hospital

Falls Church, Virginia, 22042, United States

Location

Children's Hospital of The King's Daughters

Norfolk, Virginia, 23507, United States

Location

VCU Massey Comprehensive Cancer Center

Richmond, Virginia, 23298, United States

Location

Carilion Children's

Roanoke, Virginia, 24014, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Providence Sacred Heart Medical Center and Children's Hospital

Spokane, Washington, 99204, United States

Location

Madigan Army Medical Center

Tacoma, Washington, 98431, United States

Location

West Virginia University Charleston Division

Charleston, West Virginia, 25304, United States

Location

West Virginia University Healthcare

Morgantown, West Virginia, 26506, United States

Location

Saint Vincent Hospital Cancer Center Green Bay

Green Bay, Wisconsin, 54301, United States

Location

Marshfield Medical Center-Marshfield

Marshfield, Wisconsin, 54449, United States

Location

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Princess Margaret Hospital for Children

Perth, Western Australia, 6008, Australia

Location

Perth Children's Hospital

Perth, Western Australia, 6009, Australia

Location

British Columbia Children's Hospital

Vancouver, British Columbia, V6H 3V4, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

Janeway Child Health Centre

St. John's, Newfoundland and Labrador, A1B 3V6, Canada

Location

IWK Health Centre

Halifax, Nova Scotia, B3K 6R8, Canada

Location

McMaster Children's Hospital at Hamilton Health Sciences

Hamilton, Ontario, L8N 3Z5, Canada

Location

Kingston Health Sciences Centre

Kingston, Ontario, K7L 2V7, Canada

Location

Children's Hospital

London, Ontario, N6A 5W9, Canada

Location

Children's Hospital of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

The Montreal Children's Hospital of the MUHC

Montreal, Quebec, H3H 1P3, Canada

Location

Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)

Québec, G1V 4G2, Canada

Location

Starship Children's Hospital

Grafton, Auckland, 1145, New Zealand

Location

Christchurch Hospital

Christchurch, 8011, New Zealand

Location

HIMA San Pablo Oncologic Hospital

Caguas, 00726, Puerto Rico

Location

San Jorge Children's Hospital

San Juan, 00912, Puerto Rico

Location

University Pediatric Hospital

San Juan, 00926, Puerto Rico

Location

Related Publications (3)

• Hogan LE, Bhatla T, Xu X, Gore L, Raetz EA, Bhojwani D, Teachey DT, Hunger SP, Loh ML, Brown PA, Ji L. Severe toxicity and poor efficacy of reinduction chemotherapy are associated with overall poor outcomes in relapsed B-cell acute lymphoblastic leukemia: a report from the Children's Oncology Group AALL1331 trial. Haematologica. 2025 Dec 1;110(12):2930-2941. doi: 10.3324/haematol.2025.287386. Epub 2025 Jun 26.

  PMID: 40568722 DERIVED

• Hogan LE, Brown PA, Ji L, Xu X, Devidas M, Bhatla T, Borowitz MJ, Raetz EA, Carroll A, Heerema NA, Zugmaier G, Sharon E, Bernhardt MB, Terezakis SA, Gore L, Whitlock JA, Hunger SP, Loh ML. Children's Oncology Group AALL1331: Phase III Trial of Blinatumomab in Children, Adolescents, and Young Adults With Low-Risk B-Cell ALL in First Relapse. J Clin Oncol. 2023 Sep 1;41(25):4118-4129. doi: 10.1200/JCO.22.02200. Epub 2023 May 31.

  PMID: 37257143 DERIVED

• Brown PA, Ji L, Xu X, Devidas M, Hogan LE, Borowitz MJ, Raetz EA, Zugmaier G, Sharon E, Bernhardt MB, Terezakis SA, Gore L, Whitlock JA, Pulsipher MA, Hunger SP, Loh ML. Effect of Postreinduction Therapy Consolidation With Blinatumomab vs Chemotherapy on Disease-Free Survival in Children, Adolescents, and Young Adults With First Relapse of B-Cell Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA. 2021 Mar 2;325(9):833-842. doi: 10.1001/jama.2021.0669.

  PMID: 33651090 DERIVED

Related Links

• Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive.

MeSH Terms

Conditions

Burkitt Lymphoma

Interventions

Stem Cell Transplantation; Asparaginase; Leyk; blinatumomab; N,N-dicyclohexyl-isoborneol-10-sulfonamide; Cyclophosphamide; Cytarabine; Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; Etoposide; Leucovorin; Mercaptopurine; azathiopurine; Methotrexate; merphos; Mitoxantrone; pegaspargase; Radiotherapy; Radiation; Hydrocortisone; Thioguanine; Vincristine

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Amidohydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Glucosides; Glycosides; Carbohydrates; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Sulfhydryl Compounds; Purines; Aminopterin; Anthraquinones; Anthrones; Anthracenes; Quinones; Physical Phenomena; Pregnenediones; Pregnenes; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines

Results Point of Contact

• Title: Results Reporting Coordinator
• Organization: Children's Oncology Group

resultsreportingcoordinator@childrensoncologygroup.org

16264470064

Study Officials

• Patrick A Brown

  Children's Oncology Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2014
• First Posted: April 2, 2014
• Study Start: December 17, 2014
• Primary Completion: June 30, 2021
• Study Completion (Estimated): September 16, 2026
• Last Updated: May 4, 2026
• Results First Posted: December 6, 2022

Record last verified: 2026-03

Locations

US (166); PR (3); CA (13); NZ (2); AU (2)