Adult B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Positive
Conditions
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.
Interventions
BIOLOGICALBlinatumomab
Given IV
DRUGIbrutinib
Given PO
Sponsors
University of California, Davis
National Cancer Institute (NCI)
Pharmacyclics LLC.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 * Male and female subjects who agree to use both a highly effective methods of birth control (e.g., condoms, implants, injectables, combined oral contraceptives, some intrauterine devices \[IUDs\], complete abstinence, or sterilized partner) and a barrier method (e.g. condoms, vaginal ring, sponge, etc) during the period of therapy and for 90 days after the last dose of study drug * Eligibility of patients receiving any medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of ibrutinib or blinatumomab will be determined following review of their case by the investigator
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Complete Remission (CR). | Up to about 3 months from start of study treatment. | Defined as the number of participants who achieve CR according to National Comprehensive Cancer Network (NCCN) Guidelines for Acute Lymphoblastic Leukemia (ALL), Version 2.2015 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | Up to about 8 months from start of study treatment. | Number of participants with adverse events graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 |
| Minimal Residual Disease (MRD) Negative CR/CRi Rate | Up to about 8 months from start of treatment. | Multiparameter Flow Cytometry (MFC) minimal residual disease (MRD) negative CR/CRi rate - defined as the number of CR/CRi participants with B-ALL cells comprising \< 0.01% of bone marrow mononuclear cells \[BMMC\] as measured by flow cytometry or molecular studies. |
| Overall Response Rate (ORR). | Up to 8 months from start of treatment. | Overall response rate (ORR) - defined as CR plus CR with incomplete count recovery (CRi) according to NCCN guidelines for ALL. |
| Overall Survival (OS). | From the time of first study drug administration until date of death from any cause, assessed for up to about 15.6 months. | Defined as the median OS measured from the time of first study drug administration until the date of progression or death from any cause. |
| Proportion of Patients Bridged to Allogeneic Hematopoietic Cell Transplant (Allo-HCT or CAR-T. | Time from start of treatment to date of hematopoietic cell transplant assessed for up to 8 months. | Proportion of patients bridged to allogeneic hematopoietic cell transplant (allo-HCT or CAR-T. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORBrian Jonas
University of California, Davis
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Region of Enrollment United States | 19 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 19 |
| other Total, other adverse events | 19 / 19 |
| serious Total, serious adverse events | 8 / 19 |
Outcome results
None listed