A Phase III Randomized Trial of Steroids + Tyrosine Kinase Inhibitor (TKI) Induction With Chemotherapy or Blinatumomab for Newly Diagnosed BCR-ABL-Positive Acute Lymphoblastic Leukemia (ALL) in Adults

Plain English Summary

Testing the Use of Steroids and Tyrosine Kinase Inhibitors With Blinatumomab or Chemotherapy for Newly Diagnosed BCR-ABL-Positive Acute Lymphoblastic Leukemia in Adults is a Phase 3 clinical trial sponsored by National Cancer Institute (NCI) studying B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1. This trial compares usual chemotherapy and steroids with a new combination of steroids, tyrosine kinase inhibitors, and blinatumomab for newly diagnosed BCR-ABL-positive acute lymphoblastic leukemia in adults. Eligible patients are adults aged 18-75 with newly diagnosed BCR-ABL-positive ALL. They must not have received prior chemotherapy and must meet certain health criteria. Participants will receive either chemotherapy and steroids or the new combination therapy, followed by a possible randomization to continue with one of the treatments. Patients can join if they have BCR-ABL-positive ALL, are not pregnant, and meet specific health criteria. Those with unstable epilepsy or certain organ dysfunction may not be eligible. The trial aims to enroll 348 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Eligible patients are adults aged 18-75 with newly diagnosed BCR-ABL-positive ALL. Patients must not have received prior chemotherapy and must meet specific health criteria, including liver and kidney function. Pregnant women or those who may become pregnant are not eligible due to potential harm to the fetus. Patients with unstable epilepsy or certain organ dysfunction may not be eligible. This trial is studying B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures overall survival, which means the trial aims to see if the new combination therapy can help patients live longer. The specific primary outcome measures are: Overall survival (OS) (Time between randomization and death from any cause, assessed up to 10 years from the date of registration). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial aims to fill a treatment gap by evaluating a new combination therapy for BCR-ABL-positive ALL, potentially offering better outcomes for patients. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1, where improved treatment options are needed.

Investor Insight

The market for new treatments for BCR-ABL-positive ALL is significant, with this trial potentially offering a competitive advantage over existing therapies. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.

Is This Trial Right for Me?

Ask your doctor if you have BCR-ABL-positive ALL and are a good candidate for this trial. Undergo bone marrow aspiration and biopsy as part of the screening process. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: CROSSOVER
• Masking: NONE
• Enrollment: 348 participants

Interventions

• PROCEDURE: Biospecimen Collection — Correlative studies
• BIOLOGICAL: Blinatumomab — Given IV
• PROCEDURE: Bone Marrow Aspiration and Biopsy — Undergo bone marrow aspiration and biopsy
• DRUG: Cyclophosphamide — Given IV
• DRUG: Cytarabine — Given IV or IT

Primary Outcomes

• Overall survival (OS) (Time between randomization and death from any cause, assessed up to 10 years from the date of registration)

Secondary Outcomes

• Rate of minimal residual disease (MRD) negativity (At week 15)
• Event free survival (EFS) (Time from randomization to failure to achieve induction molecular remission by week 15, confirmed molecular relapse after molecular remission or to death in remission, assessed up to 10 years from the date of registration)
• Rate of MRD negativity (After re-induction)
• Incidence of adverse events (Up to 10 years from the date of registration)

Full Eligibility Criteria

Inclusion Criteria:

* ELIGIBILITY CRITERIA FOR PRE-REGISTRATION (TO STEP 0)
* Patient must be \>= 18 and =\< 75 years of age
* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status between 0-3
* Patient must be newly diagnosed with B acute lymphoblastic leukemia (B-ALL) or is suspected to have acute lymphoblastic leukemia (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 aspirate and/or peripheral blood specimen must be submitted to the ECOG-American College of Radiology Imaging Network (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 aspirate 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, with recommendation 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
* Patient must not have a diagnosis of BCR/ABL T-ALL
* Patient must not have received chemotherapy for B-ALL. Patients who received up to five days of therapy (hydroxyurea and/or steroids of any kind) with the aim to reduce disease burden prior to study registration to Step 1 are eligible
* Patient must not have unstable epilepsy that requires treatment
* Patients with lymphoid blast crisis chronic myeloid leukemia (CML) are not eligible
* ELIGIBILITY CRITERIA FOR REGISTRATION TO STEP 1
* Patient must have a diagnosis of Philadelphia chromosome positive (Ph+) ALL that has been determined locally and bone marrow and/or peripheral blood was sent and receipt confirmed for central confirmation or determined centrally by the ECOG-ACRIN Leukemia Laboratory at MD Anderson Cancer Center
* Patient 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 patients of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy. A patient of childbearing potential is defined as any woman, regardless of 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)
* Patients 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 step 1 registration, while on study treatment, and until at least six months after the last dose of study treatment
* Total bilirubin =\< 3 mg/dL (patients with Gilbert's syndrome must have a total bilirubin =\< 5 mg/dL) (obtained =\< 28 days prior to step 1 registration)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X the institutional upper limit of normal (ULN) (obtained =\< 28 days prior to step 1 registration)
* Estimated creatinine clearance \> 45 mL/min (based on Cockcroft-Gault equation) (obtained =\< 28 days prior to step 1 registration)
* Patients with acute organ dysfunction at step 1 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
* Patients who presented with no evidence of acute organ dysfunction but during step 0 experienced a rise in liver enzymes which investigator suspects to be a side effect of any of prescribed drugs, are allowed to be registered regardless of the level of liver

Trial Locations

• University of Alabama at Birmingham Cancer Center, Birmingham, Alabama, United States
• Anchorage Associates in Radiation Medicine, Anchorage, Alaska, United States
• Anchorage Radiation Therapy Center, Anchorage, Alaska, United States
• Alaska Breast Care and Surgery LLC, Anchorage, Alaska, United States
• Alaska Oncology and Hematology LLC, Anchorage, Alaska, United States
• Alaska Women's Cancer Care, Anchorage, Alaska, United States
• Anchorage Oncology Centre, Anchorage, Alaska, United States
• Katmai Oncology Group, Anchorage, Alaska, United States
• Providence Alaska Medical Center, Anchorage, Alaska, United States
• Mercy Hospital Fort Smith, Fort Smith, Arkansas, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• BCR-ABL-positive acute lymphoblastic leukemia
• Chronic myeloid leukemia (CML)
• Acute myeloid leukemia (AML)
• Acute lymphoblastic leukemia (ALL)

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