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

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.

Conditions

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

Interventions

PROCEDURE

Biospecimen Collection

Undergo CSF and blood sample collection

BIOLOGICAL

Blinatumomab

Given IV

PROCEDURE

Bone Marrow Aspiration

Undergo bone marrow biopsy and aspiration

PROCEDURE

Bone Marrow Biopsy

Undergo bone marrow biopsy and aspiration

DRUG

Calaspargase Pegol

Given IV

PROCEDURE

Chest Radiography

Undergo chest x-ray

PROCEDURE

Computed Tomography

Undergo CT or PET/CT

DRUG

Cyclophosphamide

Given IV

DRUG

Cytarabine

Given IV or SC

DRUG

Daunorubicin Hydrochloride

Given IV

DRUG

Dexamethasone

Given PO or IV

DRUG

Doxorubicin

Given IV

PROCEDURE

Echocardiography Test

Undergo ECHO

DRUG

Leucovorin Calcium

Given PO or IV

DRUG

Mercaptopurine

Given PO

DRUG

Methotrexate

Given IT or IV

PROCEDURE

Multigated Acquisition Scan

Undergo MUGA

PROCEDURE

Positron Emission Tomography

Undergo PET/CT

DRUG

Revumenib

Given PO

DRUG

Thioguanine

Given PO

DRUG

Vincristine

Given IV

Sponsors & Collaborators

• National Cancer Institute (NCI)

  collaborator NIH

• SWOG Cancer Research Network

  lead NETWORK

Principal Investigators

• Ibrahim Aldoss · SWOG Cancer Research Network

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

1 Year

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-10-14

Primary Completion

2031-04-16

Completion

2032-04-16

FDA Drug

Yes