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Not yet recruitingNCT07636564Updated Jun 9, 2026

Testing Blinatumomab With or Without Revumenib in Patients With B-cell Acute Lymphoblastic Leukemia With a Genetic Change Requiring More Treatment

A Phase 2 interventional study of Biospecimen Collection and Blinatumomab in Acute Leukemia of Ambiguous Lineage, B Acute Lymphoblastic Leukemia and B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative, sponsored by SWOG Cancer Research Network. Not yet recruiting. Open to participants aged 1 Year and older. Per ClinicalTrials.gov, last updated 2026-06-09.

Sponsored by SWOG Cancer Research Network · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
90
Allocation
Randomized
Ages
1 Year and older
Sex
All
01

Study summary

This phase II trial tests how well adding revumenib to usual treatment (blinatumomab) compared to usual treatment alone works in treating patients with B-cell acute lymphoblastic leukemia (B-ALL) or acute leukemia with ambiguous lineage (ALAL) with KMT2A-translocation. Revumenib binds to a protein called menin and keeps it from binding to another protein called KMT2A. This stops or slows the growth of leukemia cells with changes in the KMT2A gene. Blinatumomab binds to CD19, which is found on most B cells (a type of white blood cell) and some types of leukemia cells. It also binds to a protein called CD3, which is found on T cells (another type of white blood cell). This may help the immune system kill cancer cells. In addition to blinatumomab, usual treatment also includes dexamethasone, methotrexate, cyclophosphamide, cytarabine, mercaptopurine, calaspargase pegol, doxorubicin, thioguanine, daunorubicin, vincristine and leucovorin. Dexamethasone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Methotrexate is in a class of medications called antimetabolites. It is also a type of antifolate. Methotrexate stops cells from using folic acid to make deoxyribonucleic acid (DNA) and may kill cancer cells. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's DNA and may kill cancer cells. It may also lower the body's immune response. Chemotherapy drugs, such as cytarabine, mercaptopurine, calaspargase pegol, doxorubicin, thioguanine, and daunorubicin, 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. Vincristine is in a class of medications called vinca alkaloids. It works by stopping cancer cells from growing and dividing and may kill them. Leucovorin is also being studied in the treatment of cancer. It is a type of chemoprotective agent and a type of chemosensitizing agent. Adding revumenib to usual treatment with blinatumomab may be safe, tolerable and more effective than blinatumomab alone in lowering the amount of leukemia in patients with B-ALL or ALAL with the KMT2A translocation.

Read the detailed description

PRIMARY OBJECTIVES:

I. Among participants enrolled to the safety run-in cohort, to evaluate the safety of blinatumomab with revumenib in this participant population. (Cohort A: Children [≥ 1 year] and adults with CD19-positive [CD19+] KMT2Ar B-cell acute lymphoblastic leukemia [ALL]/ acute leukemia with ambiguous lineage [ALAL] in morphological first complete remission [CR1]) II. First primary randomized objective: Among participants with positive measurable residual disease (MRD) by clonoSEQ before randomization, to compare the rates of MRD negative complete remission (CR) by clonoSEQ after the completion of one cycle of blinatumomab versus one cycle of blinatumomab plus revumenib. (Cohort A: Children [≥ 1 year] and adults with CD19-positive [CD19+] KMT2Ar B-cell acute lymphoblastic leukemia [ALL]/ acute leukemia with ambiguous lineage [ALAL] in morphological first complete remission [CR1]) III. Secondary primary randomized objective (hierarchical tested): Among participants with positive MRD by clonoSEQ before randomization, if rates of MRD negative CR by clonoSEQ after completion of one cycle of therapy are improved with blinatumomab plus revumenib versus blinatumomab, to evaluate whether MRD-event-free survival is improved among patients randomized to blinatumomab plus revumenib versus blinatumomab. (Cohort A: Children [≥ 1 year] and adults with CD19-positive [CD19+] KMT2Ar B-cell acute lymphoblastic leukemia [ALL]/ acute leukemia with ambiguous lineage [ALAL] in morphological first complete remission [CR1]) IV. To describe and evaluate the feasibility of revumenib in combination with reduced intensity multiagent chemotherapy in this participant population. (Cohort B: Untreated newly diagnosed KMT2Ar B/T-ALL or ALAL in older adults [age ≥ 55 years])

SECONDARY OBJECTIVES:

I. Within each arm and cohort and across cycles of therapy, to estimate the frequency and severity of toxicities.

II. In Cohort A: Among participants with positive MRD by clonoSEQ before randomization, to estimate the rate of MRD negative CR by clonoSEQ after two cycles of blinatumomab or blinatumomab plus revumenib.

III. In Cohort A: Among participants with negative MRD by clonoSEQ before randomization, to estimate 6-month event-free survival and MRD-event-free survival in each arm.

IV. In Cohort A: Among participants with negative MRD by clonoSEQ before randomization, to estimate 6-month event-free survival in each arm.

V. In Cohort B: To estimate the post induction composite morphological CR (CR/CR with incomplete count recovery [CRi]) rate.

VI. To estimate proportion of participants MRD negative by multi-color flow cytometry after induction (Cohort B) and cycle 1 of blinatumomab (Cohorts A + B, including the safety cohort of Cohort A).

VII. Within each arm and cohort cohort (including the safety cohort of Cohort A): To estimate the rates of lineage switch and/or CD19-negative (CD19-) relapse.

VIII. Within each arm and cohort cohort (including the safety cohort of Cohort A): To estimate the rate of allogeneic hematopoietic stem cell transplantation (HSCT) in CR1.

IX. Within each arm and cohort cohort (including the safety cohort of Cohort A): To estimate event-free survival (EFS), MRD-EFS, relapse-free survival (RFS), progression-free survival (PFS), and MRD-PFS within each arm and cohort (including the safety cohort of Cohort A) and by age ≥ 1 year to \< 18 years versus ≥ 18 years of age.

X. Within each arm and cohort cohort (including the safety cohort of Cohort A): To estimate time to MRD relapse by flow cytometry and/or clonoSEQ.

XI. Within each arm and cohort cohort (including the safety cohort of Cohort A): To estimate overall survival (OS).

TRANSLATIONAL MEDICINE OBJECTIVES:

I. To estimate the frequency of MEN1 mutations by quantitative polymerase chain reaction (qPCR) and/or high sensitivity next generation sequencing (NGS) pre-induction (Cohort B), pre-randomization (Cohort A), after blinatumomab treatment (Cohorts A and B) and at the time of relapse (Cohorts A and B). (Primary) II. To estimate the rate of KMT2A fusion reverse transcriptase (RT)-PCR MRD negativity after the first and second cycle of blinatumomab therapy within treatment arms in Cohort A. (Secondary) III. To estimate the rate of KMT2A fusion RT-PCR MRD negativity after chemotherapy induction and blinatumomab post-induction therapy in Cohort B. (Secondary) V. To estimate the rate of immunoglobulin (IG)/T cell receptor (TR) variable (V) (diversity [D]) joining (J) next generation (NGS) MRD negative remission after first and second cycle of blinatumomab across treatment cohorts in Cohort A (among those with diagnosis specimens available) and after induction and blinatumomab (if administered) in Cohort B. (Secondary) V. To descriptively report changes in gene expression between diagnosis (in Cohort B, and as available in Cohort A) and relapse samples by ribonucleic acid (RNA) sequencing of registration and relapse samples. (Secondary)

OUTLINE: Patients 1 year of age or older with B-cell ALL or ALAL are assigned to Cohort A. Patients 55 and older with B-ALL, T-ALL or ALAL are assigned to Cohort B.

COHORT A: The first 6-12 eligible patients are assigned to Arm 1. Subsequent patients are randomized to Arm 1 or Arm 2.

ARM 1:

BLINATUMOMAB AND REVUMENIB CYCLE 1 (35 DAYS): Patients receive revumenib orally (PO) twice daily (BID) on days 4-28 of cycle 1, blinatumomab intravenously (IV) continuously on days 1-28 of cycle 1, dexamethasone PO or IV on days 1 and 8 (if indicated) of cycle 1, and methotrexate intrathecally (IT) on days 1 and 15 of cycle 1.

CONSOLIDATION PART 1 AND PART 2 (56 DAYS): Patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29, cytarabine IV over 1-30 minutes or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39, mercaptopurine PO once daily (QD) on days 1-14 and 29-42, methotrexate IT on days 1, 8, 15, and 22 or on days 1, 8, 29, and 43, vincristine IV on days 15, 22, 43, and 50 and calaspargase pegol IV over 1-2 hours on days 15 and 43 in the absence of disease progression or unacceptable toxicity.

BLINATUMOMAB AND REVUMENIB CYCLE 2 (35 DAYS): Patients receive revumenib PO BID on days 1-28 of cycle 2, blinatumomab IV continuously on days 1-28 of cycle 2, dexamethasone PO or IV on day 1 of cycle 2, and methotrexate IT on days 1 and 15 of cycle 2.

INTERIM MAINTENANCE 1 (63 DAYS): Patients receive vincristine IV on days 1, 15, 29, and 43, high dose methotrexate IV over 24 hours on days 1, 15, 29, and 43, leucovorin PO or IV on days 3-4, 17-18, 31-32, and 45-46, mercaptopurine PO on days 1-14, 15-28, 29-42, and 43-56, and methotrexate IT on days 1 and 29 in the absence of disease progression or unacceptable toxicity.

DELAYED INTENSIFICATION PART 1 AND PART 2 (63 DAYS): Patients receive methotrexate IT on days 1, 29, and 36, dexamethasone PO BID or IV on days 1-7 and 15-21, vincristine IV on days 1, 8, 15, 43, and 50, doxorubicin IV over 3-15 minutes on days 1, 8, and 15, calaspargase pegol IV over 1-2 hours on days 4 and 43, cyclophosphamide IV over 30-60 minutes on day 29, thioguanine PO on days 29-42 and cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39 in the absence of disease progression or unacceptable toxicity.

INTERIM MAINTENANCE 2 (56 DAYS): Patients receive vincristine IV on days 1, 11, 21, 31, and 41, methotrexate IV on days 1, 11, 21, 31, and 41, methotrexate IT on days 1 and 31 and calaspargase pegol IV over 1-2 hours on days 2 and 23 in the absence of disease progression or unacceptable toxicity.

Additionally, patients undergo chest x-ray and echocardiography (ECHO) or multigated acquisition scan (MUGA) at screening and bone marrow biopsy and aspiration, cerebrospinal fluid (CSF) and blood sample collection, computed tomography (CT) or positron emission tomography (PET)/CT throughout the study.

ARM 2:

BLINATUMOMAB CYCLE 1 (35 DAYS): Patients blinatumomab IV continuously on days 1-28 of cycle 1, dexamethasone PO or IV on days 1 and 8 (if indicated) of cycle 1, and methotrexate IT on days 1 and 15 of cycle 1.

CONSOLIDATION PART 1 AND PART 2 (56 DAYS): Patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29, cytarabine IV over 1-30 minutes or SC on days 1-4, 8-11, 29-32, and 36-39, mercaptopurine PO QD on days 1-14 and 29-42, methotrexate IT on days 1, 8, 15, and 22 or on days 1, 8, 29, and 43, vincristine IV on days 15, 22, 43, and 50 and calaspargase pegol IV over 1-2 hours on days 15 and 43 in the absence of disease progression or unacceptable toxicity.

BLINATUMOMAB CYCLE 2 (35 DAYS): Patients receive blinatumomab IV continuously on days 1-28 of cycle 2, dexamethasone PO or IV on day 1 of cycle 2, and methotrexate IT on days 1 and 15 of cycle 2.

INTERIM MAINTENANCE 1 (63 DAYS): Patients receive vincristine IV on days 1, 15, 29, and 43, high dose methotrexate IV over 24 hours on days 1, 15, 29, and 43, leucovorin PO or IV on days 3-4, 17-18, 31-32, and 45-46, mercaptopurine PO on days 1-14, 15-28, 29-42, and 43-56, and methotrexate IT on days 1 and 29 in the absence of disease progression or unacceptable toxicity.

DELAYED INTENSIFICATION PART 1 AND PART 2 (63 DAYS): Patients receive methotrexate IT on days 1, 29, and 36, dexamethasone PO BID or IV on days 1-7 and 15-21, vincristine IV on days 1, 8, 15, 43, and 50, doxorubicin IV over 3-15 minutes on days 1, 8, and 15, calaspargase pegol IV over 1-2 hours on days 4 and 43, cyclophosphamide IV over 30-60 minutes on day 29, thioguanine PO on days 29-42, and cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39 in the absence of disease progression or unacceptable toxicity.

INTERIM MAINTENANCE 2 (56 DAYS): Patients receive vincristine IV on days 1, 11, 21, 31, and 41, methotrexate IV on days 1, 11, 21, 31, and 41, methotrexate IT on days 1 and 31 and calaspargase pegol IV over 1-2 hours on days 2 and 23 in the absence of disease progression or unacceptable toxicity.

Additionally, patients undergo chest x-ray and ECHO or MUGA at screening and bone marrow biopsy and aspiration, CSF and blood sample collection, CT or PET/CT throughout the study.

COHORT B:

INDUCTION (35 DAYS): Patients receive cytarabine IT on day 1 of cycle 1, vincristine IV on days 1, 8, 15, and 22 of cycle 1, dexamethasone PO or IV BID on days 1-7 and 15-21 or IV BID on days 1-7 of cycle 1, daunorubicin IV on days 1, 8, and 15 of cycle 1, methotrexate IT on days 8 and 29 or once weekly of cycle 1, and revumenib PO BID on days 8-28 of cycle 1.

POST-INDUCTION (84 DAYS): Patients with morphological CR after induction treatment may receive revumenib PO BID on days 4-28 of cycle 1 and on days 1-28 of cycle 2, blinatumomab IV continuously on days 1-28 of cycles 1 and 2 and methotrexate IT on days 1 and 15 of cycles 1 and 2. Cycles repeat every 42 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.

Additionally, patients undergo bone marrow biopsy and aspiration, CSF and blood sample collection, CT or PET/CT throughout the study.

After completion of study treatment, patients are followed every 3 months for the first 2 years, every 6 months for years 3-5 and then annually for up to 10 years after registration.

02

Conditions studied

  • Acute Leukemia of Ambiguous Lineage
  • B Acute Lymphoblastic Leukemia
  • B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative
  • T Acute Lymphoblastic Leukemia
03

In context

Leukemia, Biphenotypic, Acute

110 studies on the registry are indexed under Leukemia, Biphenotypic, Acute; 51 are open to participants now.

This study's planned enrollment of 90 is above the median of 50 across 98 interventional studies indexed under Leukemia, Biphenotypic, Acute.

Browse Leukemia, Biphenotypic, Acute studies →

Lead sponsor

SWOG Cancer Research Network is the lead sponsor of 328 studies on the registry; 37 are open to participants now.

Of its 17 completed or terminated interventional studies of FDA-regulated products, 17 (100%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
1 Year and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Inclusion Criteria:

  • COHORT A: Participants must meet diagnostic criteria for either B-cell acute lymphoblastic leukemia (ALL) with KMT2A-translocation or acute leukemia with ambiguous lineage (ALAL) with KMT2A-translocation
  • COHORT A: Participants must have KMT2A-translocation documented locally by conventional cytogenetics, fluorescence in situ hybridization (FISH) or molecular studies such as next generation sequencing (NGS)
  • COHORT A: Participants must have achieved morphological first complete remission (CR1) after induction cycle (s) as defined bone marrow lymphoblasts \< 5%

  • COHORT A: Participants must have either known trackable clone(s) by clonoSEQ that was identified at initial diagnosis, or a banked diagnostic sample, which can include clinical samples from the treating institution, available that can be used to identify trackable clone(s)

    • Participants must not be known not to have trackable clones by clonoSEQ
    • Participants must not be known already to have MRD-negativity by clonoSEQ prior to enrollment
  • COHORT A: Participants must have evidence of CD19 expression at any level in ALL or ALAL documented locally by flow cytometry or immunohistochemistry in bone marrow or peripheral blood at the time of initial diagnosis. Immunophenotyping of the blood or marrow lymphoblasts must be performed to determine lineage. Appropriate marker studies including CD19 (B cell) must be performed. If a bone marrow aspirate cannot be obtained despite an attempt (dry tap), appropriate Immunohistochemistry (IHC) testing, including CD19, must be performed on the bone marrow biopsy to determine lineage
  • COHORT A: Participants must have Philadelphia-chromosome negative ALL or ALAL
  • COHORT A: Participants must not have known lymphoid blast crisis arising from chronic myeloid leukemia (CML) or have received previous tyrosine kinase inhibitor (TKI) therapy for their chronic myeloid leukemia (CML)

  • COHORT B: Participants must meet diagnostic criteria for either newly diagnosed with acute lymphoblastic leukemia (ALL) or acute leukemia with ambiguous lineage (ALAL)

    • Participants with either B or T-cell subtypes of ALL are permitted on Cohort B
    • Participants must have KMT2A-translocation documented locally by conventional cytogenetics, fluorescence in situ hybridization (FISH) or molecular studies such as next generation sequencing (NGS)
  • COHORT B: Participants must have Philadelphia-chromosome negative ALL or ALAL
  • COHORT B: Participants must not have known lymphoid blast crisis arising from CML or have received previous TKI therapy for their chronic myeloid leukemia (CML)
  • COHORT A: Participants ≥ 18 years may have received 1 to 3 cycles of induction/consolidation before entering the study. It is encouraged to enroll participants immediately after completing the first induction cycle if the patient achieves morphological CR. For pediatric patients \< 18 years of age, enrollment must occur after induction therapy
  • COHORT A: Participants must discontinue strong cytochrome P450 (CYP)3A4 inhibitors or strong or moderate inducers, except corticosteroids, within 14 days prior to registration

  • COHORT A: Participants must have recovered from any prior major surgery adverse effects at least 14 days prior to registration, to the satisfaction of the local investigator

    • Note: Central venous access placement is not considered major surgery for the purposes of this protocol
  • COHORT A: Participants must not be receiving any oral or intravenous systemic immunosuppressive therapy with the exception of induction/consolidation chemotherapy for the treatment of their current ALL or ALAL. Participants may receive up to 10 mg per day of prednisone or prednisone equivalent for adrenal insufficiency or other indications
  • COHORT A: Participants must not have received a prior allogeneic hematopoietic stem cell transplant
  • COHORT A: Participants must not have received prior blinatumomab, menin inhibitors, chimeric antigen receptor (CAR)-T therapy, or anti-CD19 antibodies

  • COHORT B: Participants must not have received prior systemic therapy for ALL or ALAL, with the exception of hydroxyurea, steroid, retinoic acid, intrathecal chemotherapy, or induction chemotherapy as defined below

    • Participants who have been started on the study regimen backbone (i.e. induction therapy) before consenting and then are found to have the KMT2Ar and are eligible for the study, can be enrolled on the study as long as revumenib treatment can be started by day 8 of induction therapy
  • COHORT B: Participants must discontinue strong CYP3A4 inhibitors or strong or moderate inducers, except corticosteroids, within 14 days prior to registration

  • COHORT B: Participants must have recovered from any prior major surgery adverse effects at least 14 days prior to registration, to the satisfaction of the local investigator

    • Note: Central venous access placement is not considered major surgery for the purposes of this protocol
  • COHORT B: Participants must not be receiving any systemic oral or intravenous immunosuppressive therapy with the exception of induction chemotherapy or corticosteroid for the treatment of their current ALL or ALAL
  • COHORT B: Participants must not have received a prior allogeneic hematopoietic stem cell transplant
  • COHORT A: Participant must be ≥ 1 years old at the time of registration. There is no upper age limit
  • COHORT A: Participant must have Zubrod/Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, or Lansky/Karnofsky performance status scores of 50-100
  • COHORT A: Participants must have a complete medical history and physical exam within 28 days prior to registration
  • COHORT A: Glomerular filtration rate (GFR) ≥ 50 ml/min/1.73 m\^2 (within 14 days prior to registration)
  • COHORT A: Absolute neutrophil count ≥ 1 x 10\^3/uL (within 14 days prior to registration)
  • COHORT A: Platelets ≥ 100 x 10\^3/uL (within 14 days prior to registration)

  • COHORT A: Direct bilirubin ≤ 2.0 mg/dL (34.2 micromoles/L) (within 14 days prior to registration)

    • Note: Participants with history of Gilbert's disease must have direct bilirubin ≤ 5 x institutional upper limit of normal (ULN)
  • COHORT A: Alanine aminotransferase (ALT) ≤ 5 x institutional ULN (within 14 days prior to registration)
  • COHORT A: Participants ≥ 18 years must have a calculated creatinine clearance ≥ 50 mL/min using the following Cockcroft-Gault formula. This specimen must have been drawn and processed within 14 days prior to registration

  • COHORT A: Adequate renal function for participants \< 18 years of age is defined as:

    • A GFR ≥ 50 mL/min/1.73 m\^2, as determined by one of the following methods:

      • Estimated GFR (eGFR) ≥ 50 mL/min/1.73 m\^2 "Bedside" Schwartz formula (2009)
      • Measured GFR ≥ 50 mL/min/1.73 m\^2 (any age). If measured GFR is used, it must be performed using direct measurement with a nuclear blood sampling method or small molecule clearance method (iothalamate or other molecule per institutional standard)
  • COHORT A: Participants must have adequate cardiac function. Participants must have cardiac ejection fraction ≥ 50% by MUGA or 2 dimensional (2-D) echocardiogram or shortening fraction (SF) ≥ 27% by echocardiogram within 90 days prior to registration. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2B or better
  • COHORT A: Participants ≥ 18 years of age with a known history of human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at registration and have undetectable viral load test on the most recent test results obtained within 6 months prior to registration
  • COHORT A: Participants ≥ 18 years of age with a known history of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load while on suppressive therapy on the most recent test results obtained within 6 months prior to registration, if indicated
  • COHORT A: Participants ≥ 18 years of age with a known history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have undetectable HCV viral load test on the most recent test results obtained within 6 months prior to registration, if indicated
  • COHORT A: Participants must not have prolonged Fridericia's formula-corrected QT interval (QTcf) defined as > 450 msec on screening electrocardiogram (EKG) prior to registration
  • COHORT A: Participants must not have relapsed or refractory disease in the bone marrow (≥ 5% blasts) or extramedullary sites involvement
  • COHORT A: Participants must not have systemic fungal, bacterial, viral or other infection that is not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment) as determined by the local investigator
  • COHORT A: Participants must not have clinically significant autoimmune disease
  • COHORT A: Participants must be able to take oral medications and comply with the oral regimen Participants must be able to swallow and retain oral medications and have no known gastrointestinal disorders likely to interfere with absorption of oral medications. Administration via nasogastric/gastrostomy (NG/G)-tube is acceptable as long as oral solution is used

  • COHORT A: Participants must not have uncontrolled intercurrent illness including, but not limited to:

    • Active central nervous system status 3 (CNS3) or CNS2 (CNS leukemia)

      • Note: Participants with CNS1 or who had prior CNS2 or CNS3 are eligible if this has cleared and have become CNS-1
    • Currently requiring supplemental oxygen (more than 2 liters per minute), mechanical ventilation, vasopressors
  • COHORT A: Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen

  • COHORT A: Participants must not be pregnant or nursing. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 24 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen

    • Note: Participants of childbearing potential must have a negative pregnancy test within 7 days prior to starting treatment
  • COHORT B: Participant must be ≥ 55 years old at the time of registration
  • COHORT B: Participant must have Zubrod/ECOG performance status of 0-2
  • COHORT B: Participants must have a complete medical history and physical exam within 28 days prior to registration
  • COHORT B: GFR ≥ 50 ml/min/1.73 m\^2 (within 14 days prior to registration)

  • COHORT B: Direct bilirubin ≤ 2.0 mg/dL (34.2 micromoles/L) (within 14 days prior to registration)

    • Note: Participants with history of Gilbert's disease or elevated bilirubin is related to underlying leukemia must have direct bilirubin ≤ 5 x institutional ULN
  • COHORT B: ALT ≤ 5 x institutional ULN unless abnormal liver tests are related to underlying leukemia (within 14 days prior to registration)
  • COHORT B: Participants must have a calculated creatinine clearance ≥ 50 mL/min using the following Cockcroft-Gault formula. This specimen must have been drawn and processed within 14 days prior to registration
  • COHORT B: Participants must have adequate cardiac function. Participants must have cardiac ejection fraction ≥ 50% by MUGA or 2-D echocardiogram within 28 days prior to registration. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2B or better
  • COHORT B: Participants with a known history human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at registration and have undetectable viral load test on the most recent test results obtained within 6 months prior to registration
  • COHORT B: Participants with a known history of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load while on suppressive therapy on the most recent test results obtained within 6 months prior to registration, if indicated
  • COHORT B: Participants with a known history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have undetectable HCV viral load test on the most recent test results obtained within 6 months prior to registration, if indicated
  • COHORT B: Participants must have a lumbar puncture to determine CNS involvement of ALL within 14 days prior to registration. Intrathecal cytarabine and/or methotrexate administered prior to study registration may count as the first dose of intrathecal therapy required as part of protocol therapy
  • COHORT B: Participants must not have an active uncontrolled infection
  • COHORT B: Participants must not have prolonged QTcf defined as > 450 msec participants on screening EKG prior to registration
  • COHORT B: Participants must not have known clinical signs of bulk central nervous system involvement (CNS3c), such as facial palsy, brain/eye involvement or hypothalamic syndrome
  • COHORT B: Participants must be able to take oral medications and comply with the oral regimen Participants must be able to swallow and retain oral medications and have no known gastrointestinal disorders likely to interfere with absorption of oral medications. Administration via NG/G-tube is acceptable as long as oral solution is used
  • COHORT B: Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen

  • COHORT B: Participants must not be pregnant or nursing. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 24 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen

    • Note: Participants of childbearing potential must have a negative pregnancy test within 7 days prior to starting treatment
  • ALL COHORTS: Participants must be offered the opportunity to participate in specimen collection submitted for translational medicine work. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System

  • NOTE: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

    • Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines
    • For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations
    • This trial will use a slot reservation system to enroll the feasibility and safety run-in portions of the study for Cohort A and Cohort B. Patients planning to enroll at this portion of the study must first have a slot reserved in advance of the registration. All site staff will use OPEN to create a slot reservation
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
90 participants (estimated)

Study arms

  • Experimental
    Cohort A, Arm 1 (revumenib and blinatumomab)

    See Detailed Description.

    Procedure: Biospecimen Collection · Biological: Blinatumomab · Procedure: Bone Marrow Aspiration · Procedure: Bone Marrow Biopsy · Drug: Calaspargase Pegol · Procedure: Chest Radiography · Procedure: Computed Tomography · Drug: Cyclophosphamide · Drug: Cytarabine · Drug: Dexamethasone · Drug: Doxorubicin · Procedure: Echocardiography Test · Drug: Leucovorin Calcium · Drug: Mercaptopurine · Drug: Methotrexate · Procedure: Multigated Acquisition Scan · Procedure: Positron Emission Tomography · Drug: Revumenib · Drug: Thioguanine · Drug: Vincristine

  • Active comparator
    Cohort A, Arm 2 (blinatumomab)

    See Detailed Description.

    Procedure: Biospecimen Collection · Biological: Blinatumomab · Procedure: Bone Marrow Aspiration · Procedure: Bone Marrow Biopsy · Drug: Calaspargase Pegol · Procedure: Chest Radiography · Procedure: Computed Tomography · Drug: Cyclophosphamide · Drug: Cytarabine · Drug: Dexamethasone · Drug: Doxorubicin · Procedure: Echocardiography Test · Drug: Leucovorin Calcium · Drug: Mercaptopurine · Drug: Methotrexate · Procedure: Multigated Acquisition Scan · Procedure: Positron Emission Tomography · Drug: Thioguanine · Drug: Vincristine

  • Experimental
    Cohort B (revumenib and blinatumomab)

    See Detailed Description.

    Procedure: Biospecimen Collection · Biological: Blinatumomab · Procedure: Bone Marrow Aspiration · Procedure: Bone Marrow Biopsy · Procedure: Computed Tomography · Drug: Cytarabine · Drug: Daunorubicin Hydrochloride · Drug: Dexamethasone · Drug: Methotrexate · Procedure: Positron Emission Tomography · Drug: Revumenib · Drug: Vincristine

Interventions

  • ProcedureBiospecimen Collection

    Undergo CSF and blood sample collection

    Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

  • BiologicalBlinatumomab

    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

  • ProcedureBone Marrow Aspiration

    Undergo bone marrow biopsy and aspiration

  • ProcedureBone Marrow Biopsy

    Undergo bone marrow biopsy and aspiration

    Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

  • DrugCalaspargase Pegol

    Given IV

    Also known as: Asparaginase (Escherichia coli Isoenzyme II), Conjugate with alpha-(((2,5-Dioxo-1-pyrrolidinyl)oxy)carbonyl)-omega-methoxypoly(oxy-1,2-ethanediyl), Asparlas, Calaspargase Pegol-mknl, EZN-2285, SC-PEG E. Coli L-Asparaginase, Succinimidyl Carbonate Monomethoxypolyethylene Glycol E. coli L-Asparaginase

  • ProcedureChest Radiography

    Undergo chest x-ray

    Also known as: Chest X-ray

  • ProcedureComputed Tomography

    Undergo CT or PET/CT

    Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

  • DrugCyclophosphamide

    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

  • DrugCytarabine

    Given 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

  • DrugDaunorubicin Hydrochloride

    Given IV

    Also known as: Cerubidin, Cerubidine, Cloridrato de Daunorubicina, Daunoblastin, Daunoblastina, Daunoblastine, Daunomycin Hydrochloride, Daunomycin, hydrochloride, Daunorubicin.HCl, Daunorubicini Hydrochloridum, FI-6339, Ondena, RP-13057, Rubidomycin Hydrochloride, Rubilem

  • DrugDexamethasone

    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

  • DrugDoxorubicin

    Given IV

    Also known as: Adriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, Hydroxyldaunorubicin

  • ProcedureEchocardiography Test

    Undergo ECHO

    Also known as: EC, Echocardiography

  • DrugLeucovorin Calcium

    Given PO or IV

    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

  • DrugMercaptopurine

    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

  • DrugMethotrexate

    Given IT or IV

    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

  • ProcedureMultigated Acquisition Scan

    Undergo MUGA

    Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNV Scan, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

  • ProcedurePositron Emission Tomography

    Undergo PET/CT

    Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

  • DrugRevumenib

    Given PO

    Also known as: Menin-Mixed Lineage Leukemia Protein-Protein Interaction Inhibitor SNDX-5613, Menin-MLL Inhibitor SNDX-5613, Menin-MLL Interaction Inhibitor SNDX-5613, SNDX 5613, SNDX-5613, SNDX5613

  • DrugThioguanine

    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

  • DrugVincristine

    Given IV

    Also known as: LCR, Leurocristine, VCR, Vincrystine

06

What researchers measure

Primary outcomes

  1. Dose limiting toxicities (Safety run-in: Cohort A)

    Will be evaluated using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 6.0. Will evaluate the proportion of participants with dose limiting toxicities and exact confidence intervals.

    Time frame: During cycle 1 (cycle 1 length = 28 days)

  2. Measurable residual disease (MRD) negativity rate (Cohort A)

    Difference in proportion of participants who achieve clonoSEQ MRD status between the two arms will be compared using a two-sample proportion test.

    Time frame: Up to 35 days after start of therapy

  3. MRD-event-free survival (EFS) (Cohort A)

    Will be compared using unstratified log-rank test.

    Time frame: From date of randomization and up to 10 years

  4. Incidence of toxicities of interest (TOI) (Cohort B)

    TOI rates will be reported with exact 90% confidence intervals.

    Time frame: Up to 30 days after last dose of study treatment

Secondary outcomes

  1. Incidence of adverse events

    Frequency and severity within each arm and across cycles of therapy will be assessed using NCI CTCAE v 6.0.

    Time frame: Up to 30 days after last dose of study treatment

  2. MRD negative complete remission (CR) rate (Cohort A)

    Will be evaluated in participants with positive MRD before randomization.

    Time frame: Up to 70 days after start of therapy

  3. EFS (Cohort A)

    Will be estimated using the Kaplan-Meier method. Will be evaluated in participants with negative MRD before randomization.

    Time frame: At 6 months

  4. MRD-EFS (Cohort A)

    Will be estimated using the Kaplan-Meier method. Will be evaluated in participants with negative MRD before randomization.

    Time frame: At 6 months

  5. Composite morphological CR rate (Cohort B)

    Will be defined as CR/CR with incomplete count recovery (CRi).

    Time frame: Up to 35 days after start of therapy

  6. Proportion of participants MRD negative (Cohorts A and B)

    Will be evaluated using multi-color flow cytometry.

    Time frame: Up to 35 days after start of therapy

  7. Rate of lineage switch and/or CD19-negative relapse (within each arm and cohort cohort)

    Time frame: Up to 10 years

  8. Rate of allogeneic hematopoietic stem cell transplantation utilization (within each arm and cohort cohort)

    Time frame: Up to 10 years

  9. EFS (within each arm and cohort cohort)

    Will be reported within each arm and cohort and by age. Will be estimated using the Kaplan-Meier method.

    Time frame: From the date of trial registration/randomization until the first of death from any cause, relapse from remission, secondary malignancy, or completion of protocol therapy, assessed up to 10 years

  10. MRD-EFS (within each arm and cohort cohort)

    Will be reported within each arm and cohort and by age. Will be estimated using the Kaplan-Meier method.

    Time frame: From the date of trial registration/randomization until the first of death from any cause, relapse from remission, secondary malignancy, or completion of protocol therapy, assessed up to 10 years

  11. Relapse-free survival (within each arm and cohort cohort)

    Will be reported within each arm and cohort and by age. Will be estimated using the Kaplan-Meier method.

    Time frame: From date of trial registration until relapse from CR/CRi or death from any cause, assessed up to 10 years

  12. Progression-free survival (PFS) (within each arm and cohort cohort)

    Will be reported within each arm and cohort and by age. Will be estimated using the Kaplan-Meier method.

    Time frame: From the date of trial registration/randomization until the first of progression, death from any cause, relapse from morphologic remission, secondary malignancy, or completion of protocol therapy, assessed up to 10 years

  13. MRD-PFS (within each arm and cohort cohort)

    Will be reported within each arm and cohort and by age. Will be estimated using the Kaplan-Meier method.

    Time frame: From the date of trial registration/randomization until the first of progression, death from any cause, relapse from morphologic remission, secondary malignancy, or completion of protocol therapy, assessed up to 10 years

  14. Time to MRD relapse (within each arm and cohort cohort)

    Will be assessed using flow cytometry and/or clonoSEQ.

    Time frame: Up to 10 years

  15. Overall survival (within each arm and cohort cohort)

    Will be estimated using the Kaplan-Meier method.

    Time frame: From day of trial registration until death from any cause, assessed up to 10 years

  16. Remission rate

    Will be defined as CR/CRi/CR with partial hematological recovery) with and without MRD by flow. Will be estimated with 95% binomial confidence intervals.

    Time frame: Up to 10 years

Other outcomes

  1. Frequency of MEN1 mutations

    Will be evaluated by quantitative polymerase chain reaction (PCR) and/or high sensitivity next generation sequencing.

    Time frame: Up to 10 years after start of therapy

  2. Rate of KMT2A fusion reverse transcriptase (RT)-PCR MRD negativity within treatment arms (Cohort A)

    Time frame: After the first and second cycle of blinatumomab (cycle length = 28 days)

  3. KMT2A fusion RT-PCR MRD negativity (Cohort B)

    Time frame: Up to 90 days after start of therapy

  4. Rate of IG/TR V(D)J MRD negative remission

    Time frame: Up to 35 days after start of therapy

  5. Changes in gene expression between diagnosis (in Cohort B and as available in Cohort A) and relapse samples

    Time frame: Up to 10 years

07

Study locations

No study locations are listed for this record.

08

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 9, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT07636564
Lead sponsor
SWOG Cancer Research Network
Collaborators
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Jun 9, 2026
Start date
Oct 14, 2026 (estimated)
Primary completion
Apr 16, 2031 (estimated)
Completion
Apr 16, 2032 (estimated)
Last update
Jun 9, 2026

Study contacts

Ibrahim Aldoss
principal investigator · SWOG Cancer Research Network

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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