Tagraxofusp and Low-Intensity Chemotherapy for the Treatment of CD123 Positive Relapsed or Refractory Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

NCT05032183 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: 2021-0545NCI-2021-08859
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib/II trial studies the effects of tagraxofusp and low-intensity chemotherapy in treating patients with CD123 positive acute lymphoblastic leukemia or lymphoblastic lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Tagraxofusp consists of human interleukin 3 (IL3) linked to a toxic agent called DT388. IL3 attaches to IL3 receptor positive cancer cells in a targeted way and delivers DT388 to kill them. Chemotherapy drugs, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving tagraxofusp with chemotherapy may help control CD123 positive relapsed or refractory acute lymphoblastic leukemia or lymphoblastic lymphoma.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Participants With a Response

  Response is defined as Complete Response CR + Complete Response with inadequate count recovery (CRi) - (CR): Normalization of the peripheral blood and bone marrow with 5% or less blasts in normocellular or hypercellular marrow with a granulocyte count of 1 x 10\^9/L or above, and platelet count of 100 x 10\^9/L. Complete resolution of all sites of extramedullary disease is required for CR. (CRi): Peripheral blood and marrow results as for CR, but with incomplete recover of counts (platelets \< 100 x 10\^9/L; neutrophils \< 1 x 10\^9/L).

  Within 3 cycles of treatment initiation

Secondary Outcomes (3)

• Participants With a Complete Response

  Within 3 cycles of treatment initiation

• Relapsed-free Survival (RFS)

  Up to two years, 5 months, and 4 days

• Overall Survival

  Up to two years, 5 months, and 4 days

Study Arms (1)

Treatment (tagraxofusp, chemotherapy)

EXPERIMENTAL

See Detailed Description

Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Dexamethasone; Biological: Filgrastim-sndz; Drug: Leucovorin; Drug: Mercaptopurine; Drug: Mesna; Drug: Methotrexate; Biological: Pegfilgrastim; Drug: Prednisone; Biological: Rituximab; Biological: Tagraxofusp-erzs; 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, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (tagraxofusp, chemotherapy)

Cytarabine DRUG

Given IT

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

Treatment (tagraxofusp, chemotherapy)

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

Treatment (tagraxofusp, chemotherapy)

Filgrastim-sndz BIOLOGICAL

Given SC

Also known as: Filgrastim Biosimilar Filgrastim-sndz, Zarxio

Treatment (tagraxofusp, chemotherapy)

Leucovorin DRUG

Given IV

Also known as: Folinic acid

Treatment (tagraxofusp, chemotherapy)

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

Treatment (tagraxofusp, chemotherapy)

Mesna DRUG

Give IV

Also known as: 2-Mercaptoethanesulfonate, Sodium Salt, Ausobronc, D-7093, Filesna, Mercaptoethane Sulfonate, Mercaptoethanesulfonate, Mesnex, Mesnil, Mesnum, Mexan, Mistabron, Mistabronco, Mitexan, Mucofluid, Mucolene, UCB 3983, Uromitexan, Ziken

Treatment (tagraxofusp, chemotherapy)

Methotrexate DRUG

Given IT

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

Treatment (tagraxofusp, chemotherapy)

Pegfilgrastim BIOLOGICAL

Given SC

Also known as: Filgrastim SD-01, filgrastim-SD/01, Fulphila, HSP-130, Jinyouli, Neulasta, Neulastim, Nyvepria, Pegcyte, Pegfilgrastim Biosimilar HSP-130, Pegfilgrastim Biosimilar Nyvepria, Pegfilgrastim Biosimilar Pegcyte, Pegfilgrastim Biosimilar Udenyca, Pegfilgrastim Biosimilar Ziextenzo, pegfilgrastim-apgf, pegfilgrastim-bmez, pegfilgrastim-cbqv, Pegfilgrastim-jmdb, SD-01, SD-01 sustained duration G-CSF, Udenyca, Ziextenzo

Treatment (tagraxofusp, chemotherapy)

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

Treatment (tagraxofusp, chemotherapy)

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 ABBS, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar IBI301, Rituximab Biosimilar JHL1101, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, Rituximab Biosimilar SIBP-02, rituximab biosimilar TQB2303, rituximab-abbs, RTXM83, Truxima

Treatment (tagraxofusp, chemotherapy)

Tagraxofusp-erzs BIOLOGICAL

Given IV

Also known as: Diphtheria Toxin(388)-Interleukin-3 Fusion Protein, DT(388)-IL3 Fusion Protein, DT388IL3 fusion protein, Elzonris, IL3R-targeting Fusion Protein SL-401, SL-401, Tagraxofusp, Tagraxofusp ERZS

Treatment (tagraxofusp, chemotherapy)

Vincristine DRUG

Given IV

Also known as: Leurocristine, VCR, Vincrystine

Treatment (tagraxofusp, chemotherapy)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients 18-70 years of age with relapsed/refractory CD123+ B- or T-cell acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma. CD123 positivity may be confirmed by either flow cytometry or immunohistochemistry
• Performance status =\< 2 (Eastern Cooperative Oncology Group \[ECOG\] scale)
• Total serum bilirubin =\< 1.5 x upper limit of normal (ULN), unless due to Gilbert's syndrome, in which case patients are eligible as long as direct bilirubin =\< 2 x ULN
• Alanine aminotransferase (ALT) =\< 2.5 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) =\< 2.5 x ULN, unless due to disease involvement of the liver or hemolysis, in which case an ALT =\< 10 x ULN is acceptable
• Serum creatinine =\< 1.5 mg/dL
• Serum albumin \>= 3.2 g/dL (32 g/L). Albumin infusions are not permitted in order to enable eligibility
• 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
• Signed informed consent
• Willingness and ability to adhere to study visit schedule and other protocol requirements, including follow-up for survival assessment

You may not qualify if:

• Active serious infection not controlled by oral or intravenous antibiotics
• Known active central nervous system (CNS) leukemia
• Diagnosis of Philadelphia chromosome-positive ALL or Burkitt leukemia/lymphoma
• Active graft versus host disease (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)
• Clinically significant cardiovascular disease (e.g., uncontrolled or any New York Heart Association Class 3 or 4 congestive heart failure, uncontrolled angina, history of myocardial infarction, unstable angina or stroke within 6 months prior to study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication)
• Patients with a cardiac ejection fraction (as measured by either multigated acquisition \[MUGA\] or echocardiogram) less than the lower limit of normal
• No clinically significant abnormalities on 12-lead electrocardiogram
• Uncontrolled, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease, pulmonary hypertension) that in the opinion of the Investigator would put the patient at significant risk for pulmonary complications during the study
• 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 for 4 months after last study treatment. 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 for 4 months after last study treatment

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Burkitt Lymphoma; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Cyclophosphamide; Cytarabine; Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; Filgrastim; Granulocyte Colony-Stimulating Factor; Leucovorin; Mercaptopurine; azathiopurine; Mesna; Methotrexate; merphos; pegfilgrastim; Prednisone; deltacortene; prednylidene; Rituximab; CT-P10; tagraxofusp; Vincristine

Condition Hierarchy (Ancestors)

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

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; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Sulfhydryl Compounds; Purines; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Aminopterin; Pregnadienediols; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines

Results Point of Contact

• Title: Ghayas Issa MD./Associate Professor
• Organization: The Univeristy of Texas MD Anderson Cancer Center

GCIssa@mdanderson.org

713-745-6798

Study Officials

• Nicholas Short, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: August 23, 2021
• First Posted: September 2, 2021
• Study Start: February 17, 2022
• Primary Completion: July 31, 2024
• Study Completion: July 31, 2024
• Last Updated: August 11, 2025
• Results First Posted: August 11, 2025

Record last verified: 2025-07

Locations

US (1)