A Phase 2 Study of Ibrutinib and Blinatumomab in Relapsed and Refractory B-Cell Acute Lymphoblastic Leukemia
Overview
- Phase
- Phase 2
- Intervention
- Blinatumomab
- Conditions
- Adult B Acute Lymphoblastic Leukemia
- Sponsor
- Brian Jonas
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Rate of CR
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
This phase II trial studies how well ibrutinib and blinatumomab work in treating patients with B acute lymphoblastic leukemia that has come back or is not responding to treatment. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as blinatumomab, may interfere with the ability of cancer cells to grow and spread. Giving ibrutinib and blinatumomab may work better in treating patients with relapsed or refractory B acute lymphoblastic leukemia.
Detailed Description
PRIMARY OBJECTIVES: I. To evaluate the efficacy of ibrutinib and blinatumomab in patients with relapsed or refractory B acute lymphoblastic leukemia (B-ALL) as measured by complete response (CR) rate. SECONDARY OBJECTIVES: I. To further examine the efficacy and safety of ibrutinib and blinatumomab in patients with relapsed or refractory B-ALL as measured by overall response rate (ORR, defined as CR plus CR with incomplete count recovery \[CRi\]), relapse free survival (RFS), overall survival (OS), minimal residual disease (MRD) response, proportion of patients bridged to allogeneic hematopoietic cell transplant (allo-HCT), and toxicity.
Investigators
Brian Jonas
Principal Investigator
University of California, Davis
Eligibility Criteria
Inclusion Criteria
- •Pathologically confirmed diagnosis of relapsed or refractory B-cell acute lymphoblastic leukemia/lymphoma with measurable bone marrow lymphoblasts or biopsy-proven extramedullary site measurable by computed tomography (CT) or positron emission tomography (PET)/CT imaging; Philadelphia chromosome-positive (Ph+) B-ALL patients must have failed treatment with at least one second generation tyrosine kinase inhibitor; prior allo-HCT is allowed
- •No hematologic parameters for inclusion; transfusion-dependent patients are eligible and platelet counts should be maintained greater than 10,000/mm\^3 throughout cycles 1 and 2
- •Bilirubin less than or equal to 1.5 x upper limit of normal (ULN) (unless bilirubin rise is due to Gilbert's syndrome or B-ALL or non-hepatic origin)
- •Serum aspartate transaminase (aspartate aminotransferase \[AST\]) or alanine transaminase (alanine aminotransferase \[ALT\]) less than or equal to 3 x ULN (unless due to B-ALL)
- •Estimated creatinine clearance greater than or equal to 30 ml/min (Cockcroft-Gault) or serum creatinine less than or equal to 2 x ULN
- •Prothrombin time (PT)/international normalized ratio (INR) =\< 1.5 x ULN and partial thromboplastin time (PTT) (activated partial thromboplastin time \[aPTT\]) =\< 1.5 x ULN (unless B-ALL related)
- •Karnofsky performance status (KPS) performance status of 60% or greater
- •Ability to understand and willingness to sign an informed consent form
- •Ability to adhere to the study visit schedule and other protocol requirements
- •Female subjects who are of non-reproductive potential (i.e., post-menopausal by history - no menses for \>= 1 year; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy); female subjects of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to the first study drug administration
Exclusion Criteria
- •Diagnosis of T acute lymphoblastic leukemia (T-ALL) or Burkitt's leukemia/lymphoma
- •Patients with current evidence of active central nervous system (CNS) leukemia
- •History of treatment with ibrutinib or blinatumomab
- •Investigational therapy, chemotherapy, immunotherapy, radiotherapy, or systemic graft versus host disease (GVHD) therapy within two weeks or five half-lives (whichever is shorter); steroids, hydroxyurea and/or leukapheresis are allowed to control blast count prior to the first dose of study drug
- •Prior allo-HCT less than three months from the time of enrollment
- •Any active acute GVHD or chronic GVHD greater than grade 1
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to ibrutinib and blinatumomab or other agents used in this study
- •Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug
- •Recent culture-documented infection requiring intravenous antimicrobials that was completed =\< 7 days before the first dose of study drug or any uncontrolled active systemic infection; fever of unknown origin is not an exclusion criterion, as this may be disease-related
- •Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved to Common Terminology Criteria for Adverse Event (CTCAE, version \[v\]4.03), grade =\< 2, or to the levels dictated in the inclusion/exclusion criteria with the exception of alopecia
Arms & Interventions
Treatment (ibrutinib, blinatumomab)
INDUCTION THERAPY: Patients receive ibrutinib PO QD on days 1-49 of course 1 and days 1-42 of course 2, and blinatumomab IV on days 8-35 of course 1 and days 1-28 of course 2 in the absence of disease progression or unacceptable toxicity. CONSOLIDATION THERAPY: Patients with CR/CRi after Induction Therapy receive ibrutinib PO QD on days 1-42 and blinatumomab IV on days 1-28. Treatment repeats every 42 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive ibrutinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: Blinatumomab
Treatment (ibrutinib, blinatumomab)
INDUCTION THERAPY: Patients receive ibrutinib PO QD on days 1-49 of course 1 and days 1-42 of course 2, and blinatumomab IV on days 8-35 of course 1 and days 1-28 of course 2 in the absence of disease progression or unacceptable toxicity. CONSOLIDATION THERAPY: Patients with CR/CRi after Induction Therapy receive ibrutinib PO QD on days 1-42 and blinatumomab IV on days 1-28. Treatment repeats every 42 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive ibrutinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: Ibrutinib
Outcomes
Primary Outcomes
Rate of CR
Time Frame: Up to 91 days
Secondary Outcomes
- MRD response(Up to 6 months)
- ORR defined as CR plus CRi assessed by disease-specific response criteria(Up to 6 months)
- OS(From the time of first study drug administration until the date of progression or death from any cause, assessed for up to 6 months)
- RFS(Time from CR/CRi until the date of progression or death from any cause, assessed for up to 6 months)
- Incidence of adverse events graded according to the National Cancer Institute CTCAE v4.03(Up to 6 months)