Ibrutinib and Blinatumomab in Treating Patients With Relapsed or Refractory B Acute Lymphoblastic Leukemia

NCT02997761 | Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: 945122UCDCC#266P30CA093373NCI-2016-01882
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Adult B Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive

Outcome Measures

Primary Outcomes (1)

• Rate of CR

  Up to 91 days

Secondary Outcomes (5)

• Incidence of adverse events graded according to the National Cancer Institute CTCAE v4.03

  Up to 6 months

• 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

Study Arms (1)

Treatment (ibrutinib, blinatumomab)

EXPERIMENTAL

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.

Biological: Blinatumomab; Drug: Ibrutinib

Interventions

Blinatumomab BIOLOGICAL

Given IV

Also known as: Anti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody, Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103, Blincyto, MEDI-538, MT-103

Treatment (ibrutinib, blinatumomab)

Ibrutinib DRUG

Given PO

Also known as: BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765

Treatment (ibrutinib, blinatumomab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia
• History of stroke or intracranial hemorrhage within 6 months prior to enrollment
• Active infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV); subjects who are positive for hepatitis B core antibody, hepatitis B surface antigen, or hepatitis C antibody must have a negative polymerase chain reaction (PCR) result before enrollment; those who are PCR positive will be excluded; subjects with HIV must have a CD4 count at or above the institutional lower limit of normal and not taking prohibited CYP3A strong inhibitors
• Major surgery within 4 weeks of first dose of study drug
• Any life-threatening illness, medical condition, or organ system dysfunction, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active autoimmune disorder, or psychiatric illness/social situations that, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk; currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to enrollment
• History of other malignancies, except for malignancy surgically resected (or treated with other modalities) with curative intent, adequately treated in situ carcinoma of the breast or cervix uteri, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; malignancy treated with curative intent with no known active disease present for \>= 3 years
• Concomitant use of warfarin or other Vitamin K antagonists

Sponsors & Collaborators

• Brian Jonas: lead
• National Cancer Institute (NCI): collaborator
• Pharmacyclics LLC.: collaborator

Study Sites (1)

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

RECRUITING

MeSH Terms

Conditions

Burkitt Lymphoma

Interventions

blinatumomab; N,N-dicyclohexyl-isoborneol-10-sulfonamide; ibrutinib

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Brian Jonas

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 12, 2016
• First Posted: December 20, 2016
• Study Start: June 27, 2017
• Primary Completion: February 1, 2025
• Study Completion: September 1, 2025
• Last Updated: May 29, 2024

Record last verified: 2024-05

Locations

US (1)