Testing the Use of Steroids and Tyrosine Kinase Inhibitors With Blinatumomab or Chemotherapy for Newly Diagnosed BCR-ABL-Positive Acute Lymphoblastic Leukemia in Adults

• Status: Recruiting
• Trial end date: 2028-07-01
• Target enrollment: 0
• Participant gender: All

Summary

This phase III trial compares the effect of usual treatment of chemotherapy and steroids and a tyrosine kinase inhibitor (TKI) to the same treatment plus blinatumomab. Blinatumomab is a Bi-specific T-Cell Engager ('BiTE') that may interfere with the ability of cancer cells to grow and spread. The information gained from this study may help researchers determine if combination therapy with steroids, TKIs, and blinatumomab work better than the standard of care.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Antibodies; Antibodies, Bispecific; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; BB 1101; Blinatumomab; Cortisone; Cyclophosphamide; Cytarabine; Dasatinib; Dexamethasone; Dexamethasone acetate; Doxorubicin; Ichthammol; Immunoglobulins; Liposomal doxorubicin; Mesna; Methotrexate; Muromonab-CD3; Ponatinib; Prednisone; Vincristine

Criteria

Inclusion Criteria:

• PREREGISTRATION (STEP 0) ELIGIBILITY CRITERIA - INCLUSION

• Patient must be newly diagnosed with B-ALL or is suspected to have ALL

• Patient must have BCR-ABL1 positive disease. The diagnosis of ALL and the presence of BCR-ABL translocation must be confirmed centrally. Patients can be registered and begin Step 1 therapy while awaiting central laboratory eligibility confirmation

• NOTE: Bone marrow and/or peripheral blood specimen must be submitted to the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) Leukemia Laboratory at MD Anderson Cancer Center to determine patient's eligibility for registration to Step 1 or confirm patient evaluability. Centrally fluorescence-activated cell sorting (FACS) analysis will be performed to determine B-ALL and to exclude acute myeloid leukemia (AML) or acute bi-phenotypic leukemia and baseline BCR-ABL status will be determined by fluorescent in situ hybridization (FISH). The ECOG-ACRIN Leukemia Laboratory will forward results within 48 hours of receipt of the specimen to the submitting institution. Bone marrow is to be from first pull (initial or re-direct). Specimens must contain sufficient blast cells. In cases where the bone marrow aspiration may be inadequate, or the bone marrow examination has already been performed prior to study consent and enrollment on Step 0, peripheral blood may be submitted, given that adequate circulating blasts are present (> 10%). If a diagnosis of BCR-ABL positive B-ALL has already been established by local Clinical Laboratory Improvement Act (CLIA) certified laboratories, the patient may be registered to Step 1 without waiting for central confirmation

• Patients who started any kind of TKI prior to study registration are allowed to proceed on the study if they received no more than 14 days of TKI

• STEP 1 REGISTRATION ELIGIBILITY CRITERIA - INCLUSION

• The diagnosis of Philadelphia chromosome positive (Ph+) ALL has been determined locally, and bone marrow and/or peripheral blood was sent for central confirmation or determined centrally by the ECOG-ACRIN Leukemia Laboratory at MD Anderson Cancer Center

• Total bilirubin =< 3 mg/dL (unless related to Gilbert's syndrome in which case total bilirubin must be =< 5 mg/dL)

• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X the institutional upper limit of normal (ULN)

• Estimated creatinine clearance > 45 mg/min (based on Cockcroft-Gault equation)

• Patients with acute organ dysfunction at registration, which may be attributed to leukemia can be registered regardless of lab results at presentation. Such patients will be allowed to register and can start Arm A steroid + TKI therapy but will only be allowed to proceed to Step 2 randomization if the eligibility criteria outlined is met

• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial

• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable or on suppressive therapy, if indicated

• Patients with a history of hepatitis C virus (HCV) infection must have an undetectable HCV viral load and if indicated, on treatment

• Patients with a prior malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial

• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients must be class 2B or better

• Investigators must confirm which TKI patient is to receive

• NOTE: Patients with known T315I mutation status should receive ponatinib treatment

• NOTE: In situations due to insurance coverage issues and the pre-selected TKI is not immediately available, patients can receive dasatinib or imatinib during Step

1. The investigator must re-specify dasatinib or ponatinib prior to Step 2 randomization and from then on patients must receive the pre-selected TKI only

• STEP 2: RANDOMIZATION - ELIGIBILITY CRITERIA - INCLUSION

• Patient must have completed at least 7 of 21 days of protocol-treatment on Arm A prior to randomization

• NOTE: First day of steroids prescription after registration will be considered as the first day of study therapy. The selected TKI should be initiated prior to randomization

• Patients who presented with acute organ dysfunction at Step 1 must have their total bilirubin and AST (SGOT)/ALT (SGPT) reduce to < 2 X institutional ULN and have an estimated creatinine clearance > 45 mg/min (based on Cockcroft-Gault equation)

• Investigators must confirm which TKI patient is to receive.

• NOTE: Patients with known T315I mutation status should receive ponatinib treatment

• For patients under age 70, intended chemotherapy regimen must have been determined prior to randomization

• STEP 3: REGISTRATION (RE-INDUCTION) - ELIGIBILITY CRITERIA - INCLUSION

• Institution has received centralized MRD results confirming positive status

• Patients who presented with acute organ dysfunction must have their total bilirubin and AST (SGOT)/ALT (SGPT) reduce to < 2 X institutional ULN

• Patients who presented with acute organ dysfunction must have an estimated creatinine clearance > 45 mg/min (based on Cockcroft-Gault equation)

• Investigators must confirm which TKI patient is to receive

• NOTE: Patients with known T315I mutation status should receive ponatinib treatment

• For patients under age 70 and previously assigned to Arm C, intended chemotherapy regimen must have been determined

Exclusion Criteria:

• PREREGISTRATION (STEP 0) ELIGIBILITY CRITERIA - EXCLUSION

• Patient must not have received chemotherapy for B-ALL. Patients who received up to five days of hydroxyurea or steroids of any kind with the aim to reduce disease burden prior to study registration are eligible

• Patient must not have unstable epilepsy that requires treatment

• STEP 1 REGISTRATION ELIGIBILITY CRITERIA - EXCLUSION

• Women must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy. A female of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)

• Women of childbearing potential and sexually active males must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse from the time of registration, while on study treatment, and until at least six months after the last dose of study treatment

• Patient must not have active concomitant malignancy. Patients on chronic hormonal therapy for breast or prostate cancer or patients treated with maintenance with targeted agents but are in remission with no evidence for the primary malignancies can be included

• Patients must not have complaints of symptoms and/or have clinical and/or radiological signs that indicate an uncontrolled infection or any other concurrent medical condition that could be exacerbated by the treatment or would seriously complicate compliance with the protocol

• STEP 2: RANDOMIZATION - ELIGIBILITY CRITERIA - EXCLUSION

• Patient must not have active central nervous system (CNS) involvement by leukemic blasts. Patients with signs of CNS involvement at presentation are eligible for randomization if clearance of blasts from the cerebrospinal fluid (CSF) is demonstrated