ALL Backbone in AYAs

NCT07227584 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 25-533
• Study Type: interventional
• Target: 67
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this research study is to evaluate a chemotherapy regiment for the treatment of newly diagnosed Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL) in adolescents and young adults (AYAs). The names of the study drugs involved in this study are:

• blinatumomab (a type of immunotherapy drug)
• cyclophosphamide (a type of chemotherapy drug)
• cytarabine (a type of antineoplastic agent)
• dexamethasone (a type of synthetic glucocorticoid)
• doxorubicin (a type of antineoplastic agent)
• etoposide (a type of antineoplastic agent)
• mercaptopurine (a type of antineoplastic agent)
• methotrexate (a type of chemotherapy drug)
• pegaspargase (a type of antineoplastic agent)
• vincristine (a type of antineoplastic agent)

Conditions

Acute Lymphoblastic Leukemia; Philadelphia Chromosome-Negative Lymphoblastic Leukemia; Acute Lymphoblastic Leukemia (ALL); Leukemia

Keywords

Acute Lymphoblastic Leukemia; Philadelphia Chromosome-Negative lymphoblastic leukemia; Acute Lymphoblastic Leukemia (ALL); Leukemia

Outcome Measures

Primary Outcomes (1)

• Treatment Completion Rate Through Time Point 3 (TP3)

  Treatment completion rate through TP3 is defined as the proportion of Adolescents and Young Adults (AYAs) participants who receive all protocol-specified therapy through TP3, without early discontinuation.

  Timeframe for TP3 depends on disease immunophenotype. Participants with CD19-positive B-ALL, TP3 occurs at the end of Blinatumomab Cycle 2 on Day 28 (130 days from study start). For participants with T-cell ALL or those who do not receive blinatum

Secondary Outcomes (16)

• Rate of Treatment-Related Mortality (TRM)

  Up to 115 weeks

• Rate of Treatment Discontinuation due to Toxicity or Disease

  Up to 115 weeks

• Rate of Asparaginase Non-Completion

  This endpoint is assessed during Consolidation II, which occurs approximately from Day 270 to Day 480 of study treatment.

• Reason of Asparaginase Non-Completion

  Up to 115 weeks

• Grade 3 Infections Toxicity Rate

  Adverse events will be followed for 30 days after completion of protocol treatment, with the overall treatment period up to 115 weeks.

Study Arms (2)

ALL Backbone Regimen for B-Cell

EXPERIMENTAL

* Steroid Prophase (3-dy cycle): Dexamethasone \& cytarabine * Induction IA (29-dy cycle): Vincristine, dexamethasone, pegaspargase, doxorubicin, IT chemotherapy * Induction IB (42-dy cycle): Cyclophosphamide, cytarabine, mercaptopurine, IT chemotherapy * Blinatumomab Cycle 1, 2 (42-dy cycles): Blinatumomab, dexamethasone, IT chemotherapy * Consolidation I: * Phase IA (28-dy cycle), Phase IC (21-dy cycle): Vincristine, mercaptopurine, methotrexate, dexamethasone, cytarabine, etoposide, pegaspargase, IT chemotherapy * Blinatumomab Cycle 3 (42-dy cycle): Dexamethasone, Blinatumomab, IT chemotherapy * Consolidation II (21-dy cycles for 30 wks): Vincristine, dexamethasone, mercaptopurine, doxorubicin, methotrexate, pegaspargase, IT chemotherapy * Blinatumomab Cycle 4 (42-dy cycle): Dexamethasone, Blinatumomab, IT chemotherapy * Continuation (21-dy cycles): Vincristine, dexamethasone, mercaptopurine, methotrexate, IT chemotherapy * End of treatment visit * Follow up

Drug: Blinatumomab; Drug: Oncaspar; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Dexamethasone; Drug: Doxorubicin Hydrochloride; Drug: Etoposide; Drug: Mercaptopurine; Drug: Methotrexate

ALL Backbone Regimen for T-Cell

EXPERIMENTAL

* Steroid Prophase (3-day cycle): Dexamethasone and cytarabine * Induction IA (29-day cycle): Vincristine, dexamethasone, pegaspargase, doxorubicin, IT chemotherapy * Induction IB (42-day cycle): Cyclophosphamide, cytarabine, mercaptopurine, IT chemotherapy * Consolidation I: * Phase IA (28-day cycle) and Phase IC (21-day cycle): Vincristine, mercaptopurine, methotrexate, dexamethasone, cytarabine, etoposide, pegaspargase, IT chemotherapy * CNS Phase (21-day cycle): Dexamethasone, vincristine, mercaptopurine, pegaspargase, IT chemotherapy * Consolidation II (21-day cycles for 30 weeks): Vincristine, dexamethasone, mercaptopurine, doxorubicin, methotrexate, pegaspargase, IT chemotherapy * Continuation (21-day cycles): Vincristine, dexamethasone, mercaptopurine, methotrexate, IT chemotherapy * End of treatment visit * Follow up

Drug: Blinatumomab; Drug: Oncaspar; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Dexamethasone; Drug: Doxorubicin Hydrochloride; Drug: Etoposide; Drug: Mercaptopurine; Drug: Methotrexate; Drug: Vincristine

Interventions

Blinatumomab DRUG

A bispecific T-cell engager (BiTE) antibody, single-use vial via intravenous infusion, per standard of care

Also known as: Blincyto, NSC# 765986

ALL Backbone Regimen for B-Cell; ALL Backbone Regimen for T-Cell

Oncaspar DRUG

A modified enzyme L-asparaginase, single-use vial via intravenous infusion, per standard of care

Also known as: PEGASPARGASE, NSC #624239)

ALL Backbone Regimen for B-Cell; ALL Backbone Regimen for T-Cell

Cyclophosphamide DRUG

An alkylating agent, single-use vial via intravenous infusion, per standard of care

Also known as: Cytoxan, NSC #26271

ALL Backbone Regimen for B-Cell; ALL Backbone Regimen for T-Cell

Cytarabine DRUG

An antineoplastic antimetabolite, multi-dose vial via intrathecal injection (through the spinal space), per standard of care

Also known as: Cytosine Arabinoside, Ara-C, Cytostar, NSC#63878

ALL Backbone Regimen for B-Cell; ALL Backbone Regimen for T-Cell

Dexamethasone DRUG

A synthetic glucocorticoid, tablets or single-use vials via orally or intravenous infusion (through the vein), per standard of care

Also known as: Decadron, Hexadrol, Dexone, Dexameth, NSC#34521

ALL Backbone Regimen for B-Cell; ALL Backbone Regimen for T-Cell

Doxorubicin Hydrochloride DRUG

An anthracycline antibiotic, single-use or multi-dose vials via intravenous infusion, per standard of care

Also known as: Adriamycin, NSC#123127

ALL Backbone Regimen for B-Cell; ALL Backbone Regimen for T-Cell

Etoposide DRUG

A derivative of podophyllotoxin, multi-dose vial via intravenous infusion, per standard of care

Also known as: VePesid, Etopophos, VP-16, NSC#141540

ALL Backbone Regimen for B-Cell; ALL Backbone Regimen for T-Cell

Mercaptopurine DRUG

A purine antagonist, tablet via orally, per standard of care

Also known as: 6-MP, Purinethol, 6-Mercaptopurine, Purixan, NSC#000755

ALL Backbone Regimen for B-Cell; ALL Backbone Regimen for T-Cell

Methotrexate DRUG

A folate analogue, multi-dose and single-use vials via intrathecal injection, per standard of care

Also known as: MTX, Amethopterin, Trexall, NSC#000740

ALL Backbone Regimen for B-Cell; ALL Backbone Regimen for T-Cell

Vincristine DRUG

A vinca alkaloid, single-use vials via intravenous injection, per standard of care

Also known as: Oncovin, VCR, LCR, NSC#67574

ALL Backbone Regimen for T-Cell

Eligibility Criteria

• Age: 18 Years - 51 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Confirmed diagnosis of Philadelphia chromosome-negative acute lymphoblastic leukemia.
• Diagnosis should be made by peripheral blood, bone marrow aspirate, bone marrow biopsy, or tissue biopsy demonstrating ≥25% involvement by lymphoblasts, with flow cytometry or immunohistochemistry confirming B-ALL or T-ALL.
• o Participants with B-cell and T-cell lymphoblastic lymphoma are eligible regardless of bone marrow involvement Participants with mixed phenotype acute leukemia (MPAL) ARE eligible, if an ALL regimen is felt to be most appropriate treatment.
• Participants with CNS leukemia ARE eligible. 3.1.2 Allowed prior therapy:
• Corticosteroids, hydroxyurea, all-trans retinoic acid (ATRA).
• IT chemotherapy.
• Emergent radiation therapy or leukapheresis for life threatening complications.
• One cycle of prior chemotherapy (i.e. an induction cycle given at another institution and participant transfers care for post-induction treatment; OR a participant does not meet eligibility prior to induction but does meet eligibility after remission induction).
• Age 18.00 - 50.99 years 3.1.4 Direct bilirubin \<1.4 mg/dL (total bilirubin \< 1.4 mg/dL is acceptable). 3.1.5 Willingness to use effective means of birth control. The effects of chemotherapy on the developing human fetus are unknown. For this reason and because therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of study.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Philadelphia chromosome-positive / BCR::ABL1 fusion 3.2.2 Participants with mature B-cell (Burkitt's) ALL. Mature B-cell ALL is defined by the presence of surface immunoglobulin AND any of the following: t(8;14)(q24;q32), t(8;22), t(2;8), or c-myc-gene rearrangement by FISH, PCR or other testing. \[FISH/PCR testing for c-myc rearrangements is not required prior to study entry, but it is suggested for participants with surface immunoglobulin expression or L3 morphology\]. 3.2.3 Participants with acute undifferentiated leukemia. 3.2.4 Participants receiving any other investigational agent for this condition.
• Uncontrolled intercurrent illness including but not limited to ongoing infection with vital sign instability (hypotension, respiratory insufficiency), life-threatening acute tumor lysis syndrome (e.g., with renal failure), symptomatic congestive heart failure, cardiac arrhythmia, intracranial or other uncontrolled bleeding. Circumstances that may significantly interfere with a participant's ability to safely comply with study procedures, such as attend scheduled study visits, adhere to treatment protocols, or complete study assessments. These include a lack of reliable transportation, unstable housing, or psychiatric illness, but reasonable attempts should be made to overcome these circumstances, including but not limited to identifying sponsor, institutional, or thirdparty financial or social support as well as psychiatric consultation for objective assessment. 3.2.6 Sexually active participants of reproductive potential who have not agreed to use an effective contraceptive method for the duration of study participation are ineligible.
• Pregnant women are excluded from this study because many of the agents used on this protocol have potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these chemotherapy agents, breastfeeding should be discontinued if the mother is enrolled.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia

Interventions

blinatumomab; pegaspargase; Cyclophosphamide; Cytarabine; Dexamethasone; Calcium Dobesilate; Doxorubicin; Etoposide; etoposide phosphate; Mercaptopurine; Methotrexate; Vincristine

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System 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; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Aminoglycosides; Glycosides; Carbohydrates; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Sulfhydryl Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Aminopterin; Pterins; Pteridines; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines

Study Officials

• Marlise R Luskin, MD, MSCE

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marlise R Luskin, MD, MSCE

CONTACT

617-632-1906; marlise_luskin@dfci.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 10, 2025
• First Posted: November 12, 2025
• Study Start: April 1, 2026
• Primary Completion (Estimated): July 31, 2030
• Study Completion (Estimated): July 31, 2035
• Last Updated: November 12, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu