Low-Intensity Chemotherapy and Venetoclax in Treating Patients With Relapsed or Refractory B- or T-Cell Acute Lymphoblastic Leukemia

NCT03808610 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2016-0629NCI-2018-03360
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the side effects and best dose of venetoclax and how well it works in combination with low-intensity chemotherapy in patients with B- or T-cell acute lymphoblastic leukemia that has not responded to treatment or that has come back. Venetoclax may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, including vincristine, cyclophosphamide, dexamethasone, rituximab, methotrexate, and cytarabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving venetoclax with low-intensity chemotherapy may work better in treating patient with B- or T-cell acute lymphoblastic leukemia.

Conditions

Recurrent T Acute Lymphoblastic Leukemia; Refractory B Acute Lymphoblastic Leukemia; Refractory T Acute Lymphoblastic Leukemia; Recurrent B Acute Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD) (Phase I)

  The MTD is the highest dose level in which \< 2 patients of 6 develop first cycle dose-limiting toxicity (DLT).

  Up to 28 days

• DLT (Phase I)

  A non-hematologic DLT is defined as a clinically significant (as assessed by treating physician) grade 3 or 4 adverse event or abnormal laboratory value (according to Common Terminology Criteria for Adverse Events \[CTCAE\] criteria). Toxicity type, severity and attribution will be summarized for each patient using frequency tables.

  Up to 28 days

Secondary Outcomes (6)

• Overall response rate (Phase II)

  Up to 56 days (2 courses)

• Minimal residual disease (MRD) negativity

  Up to 4 years

• Duration of response (DOR)

  Up to 4 years

• Event-free survival (EFS)

  From the first day of treatment until any failure (resistant disease, relapse, or death), assessed up to 4 years

• Overall survival (OS)

  From the first day of treatment to time of death from any cause, assessed up to 4 years

Other Outcomes (1)

• Apoptotic protein expression and Bcl-2 dependency

  Up to 4 years

Study Arms (1)

Experimental (venetoclax, vincristine, cyclophosphamide)

EXPERIMENTAL

See Detailed Description.

Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Dexamethasone; Drug: Methotrexate; Drug: Nelarabine; Drug: Pegaspargase; Drug: Prednisone; Biological: Rituximab; Drug: Venetoclax; Drug: Vincristine

Interventions

Cyclophosphamide DRUG

Given IV

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

Experimental (venetoclax, vincristine, cyclophosphamide)

Cytarabine DRUG

Given IV

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

Experimental (venetoclax, vincristine, cyclophosphamide)

Dexamethasone DRUG

Given IV or PO

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, Fluorodelta, Fortecortin, Gammacorten, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex

Experimental (venetoclax, vincristine, cyclophosphamide)

Methotrexate DRUG

Given IV

Also known as: Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate, CL 14377, CL-14377, Emtexate, Emthexat, Emthexate, Farmitrexat, Fauldexato, Folex, Folex PFS, 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

Experimental (venetoclax, vincristine, cyclophosphamide)

Nelarabine DRUG

Given IV

Also known as: 2-Amino-6-methoxypurine arabinoside, 506U78, Arranon, Compound 506U78, GW506U78

Experimental (venetoclax, vincristine, cyclophosphamide)

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

Experimental (venetoclax, vincristine, cyclophosphamide)

Prednisone DRUG

Given PO

Also known as: .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl, Dacortin, DeCortin, Decortisyl, Decorton, Delta 1-Cortisone, Delta-Dome, Deltacortene, Deltacortisone, Deltadehydrocortisone, Deltasone, Deltison, Deltra, Econosone, Lisacort, Meprosona-F, Metacortandracin, Meticorten, Ofisolona, Orasone, Panafcort, Panasol-S, Paracort, Perrigo Prednisone, PRED, Predicor, Predicorten, Prednicen-M, Prednicort, Prednidib, Prednilonga, Predniment, Prednisone Intensol, Prednisonum, Prednitone, Promifen, Rayos, Servisone, SK-Prednisone

Experimental (venetoclax, vincristine, cyclophosphamide)

Rituximab BIOLOGICAL

Given IV

Also known as: ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Rituxan, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar IBI301, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, rituximab biosimilar TQB2303, rituximab-abbs, RTXM83, Truxima

Experimental (venetoclax, vincristine, cyclophosphamide)

Venetoclax DRUG

Given PO

Also known as: ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto

Experimental (venetoclax, vincristine, cyclophosphamide)

Vincristine DRUG

Given IV

Also known as: LEUROCRISTINE, VCR, Vincrystine

Experimental (venetoclax, vincristine, cyclophosphamide)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of one of the following
• Patients ≥ 18 years of age with relapsed/refractory B- or T-cell ALL (for phase II only)
• Patients ≥ 60 years of age with previously untreated B- or T-cell ALL. Patients \<60 years of age may be enrolled if they are considered unfit for intensive chemotherapy
• Patients ≥ 60 years of age with previously treated B- or T-cell ALL who received 1-2 courses of any frontline chemotherapy. Patients \<60 years of age may be enrolled if they are considered unfit for intensive chemotherapy
• If they achieved CR/CRi, they are assessable only for event-free and overall survival
• If they failed to achieve CR/CRi, they are assessable for response, event-free, and overall survival
• Performance status ≤ 3 (Eastern Cooperative Oncology Group \[ECOG\] Scale)
• Adequate liver and renal function as defined by the following criteria:
• Total serum bilirubin ≤ 1.5 x upper limit of normal (ULN)
• Alanine aminotransferase (ALT) ≤ 3 x ULN, unless due to disease involvement of the liver or hemolysis, in which case an ALT ≤ 10 x ULN is acceptable
• Aspartate aminotransferase (AST) ≤ 3 x ULN, unless due to disease involvement of the liver or hemolysis, in which case an ALT ≤ 10 x ULN is acceptable
• Creatinine clearance ≥ 30 mL/min
• INR ≤ 1.5 x ULN and aPTT . 1.5 x ULN
• For females of childbearing potential, a negative pregnancy test must be documented within 1 week of starting treatment
• Female and male patients who are fertile must agree to use an effective form of contraception (birth control methods while on study, such as birth control pills or injections, intrauterine devices \[IUDs\]), or double-barrier methods (for example, a condom in combination with spermicide) with their sexual partners for 4 months after the end of treatment

You may not qualify if:

• Patients with Philadelphia chromosome-positive ALL or Burkitt leukemia
• Patients who are willing and eligible to receive intensive chemotherapy (only for patients enrolling in frontline cohort)
• Active serious infection not controlled by oral or intravenous antibiotics
• Known CNS leukemia requiring radiation
• Active GVHD
• Active secondary malignancy other than skin cancer (e.g., basal cell carcinoma or squamous cell carcinoma) that in the investigator's opinion will shorten survival to less than 1 year
• Known hepatitis B or C infection, or known seropositivity for human immunodeficiency virus (HIV)
• Active grade III-V cardiac failure as defined by the New York Heart Association Criteria
• Patients with a cardiac ejection fraction (as measured by either multigated acquisition \[MUGA\] or echocardiogram) \< 40%
• Received moderate or strong CYP3A inhibitors or strong CYP3A inducers within 7 days of starting venetoclax
• Received medication that interferes with coagulation or platelet function within 7 days prior to the first dose of study drug or during the study treatment period
• Consumed grapefruit, grapefruit products, Seville oranges, or star fruit within 3 days prior to starting venetoclax
• Prior history of treatment with navitoclax.
• Pregnant and lactating women will not be eligible; women of childbearing potential should have a negative pregnancy test prior to entering on the study and be willing to practice methods of contraception. Women do not have childbearing potential if they have had a hysterectomy or are postmenopausal without menses for 12 months. In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control
• History of significant bleeding disorder unrelated to cancer, including: diagnosed congenital bleeding disorders (e.g., von Willebrand's disease); diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Short NJ, Jabbour E, Jain N, Senapati J, Nasr L, Haddad FG, Li Z, Hsiao YC, Yang JJ, Pemmaraju N, Ohanian M, Wierda WG, Montalban-Bravo G, Borthakur G, Han L, Xiao L, Huang X, Abramova R, Zhao M, Garris R, Konopleva M, Ravandi F, Kantarjian H. A phase 1/2 study of mini-hyper-CVD plus venetoclax in patients with relapsed/refractory acute lymphoblastic leukemia. Blood Adv. 2024 Feb 27;8(4):909-915. doi: 10.1182/bloodadvances.2023012231.

  PMID: 38207208 DERIVED

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Burkitt Lymphoma; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Cyclophosphamide; Cytarabine; Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; Methotrexate; merphos; nelarabine; pegaspargase; Prednisone; deltacortene; prednylidene; Rituximab; CT-P10; venetoclax; 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; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia; Hematologic Diseases

Intervention Hierarchy (Ancestors)

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; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienediols; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines

Study Officials

• Elias Jabbour

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2019
• First Posted: January 17, 2019
• Study Start: April 3, 2019
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 9, 2026

Record last verified: 2026-01

Locations

US (1)