Obinutuzumab With High-dose Ibrutinib for the Treatment of Patients With Chronic Lymphocytic Leukemia With Progressive Disease on Single Agent Ibrutinib.

NCT02611908 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: 151231
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of the study is to investigate whether the combination of obinutuzumab and ibrutinib (administered up to 840 mg per day) might be useful for the treatment of CLL or SLL that is not responding or no longer responding to treatment with ibrutinib alone. The study will evaluate whether this regimen can reduce the amount of cancerous cells in the body. Subjects will be treated with ibrutinib at a dose of up to 840 mg a day by mouth, as well as obinutuzumab infusions. Although both of these agents are approved by the FDA for the treatment of CLL or SLL, the combination and the dosing schedule of ibrutinib are considered experimental.

Conditions

Chronic Lymphocytic Leukemia

Keywords

CLL; cancer; obinutuzumab; ibrutinib; SLL

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose

  2 months

Secondary Outcomes (4)

• Treatment-emergent adverse events

  2 years

• overall response rate

  2 months

• progression free survival

  2 months

• stable disease rate

  2 months

Study Arms (1)

ibrutinib +obinutuzumab

EXPERIMENTAL

Drug: ibrutinib; Drug: obinutuzumab

Interventions

ibrutinib DRUG

Cohort 1 420 mg PO daily Cohort 2 560 mg PO daily Cohort 3 700 mg PO daily Cohort 4 840 mg PO daily

Also known as: Imbruvica

ibrutinib +obinutuzumab

obinutuzumab DRUG

obinutuzumab 100 mg IV on day 1, 900mg IV on day 2, 1000mg IV day 8, 15, 28 then q 28 days for a total of 8 doses.

Also known as: Gazyva

ibrutinib +obinutuzumab

Eligibility Criteria

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

You may qualify if:

• Clinical and phenotypic verification of B cell CLL or SLL and measurable disease.
• Prior therapy: Patients must have been receiving single agent ibrutinib therapy at the time of disease progression. Patient may have received other therapy in combination with ibrutinib earlier in the their treatment course. Prior obinutuzumab therapy is also permitted.
• Progressive disease on current single agent ibrutinib therapy (but not within the first 2 months of initiating ibrutinib therapy). Progression is based on 2008 iwCLL definition.
• ECOG performance status of 0-2.
• Adequate hematologic function.
• Adequate renal function.
• Adequate hepatic function.

You may not qualify if:

• Known CNS lymphoma or leukemia
• History of Richter's or prolymphocytic transformation.
• Primary ibrutinib resistance, defined by progressive disease within the first 2 months of first initiating ibrutinib therapy.
• Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenia purpura (ITP)
• CLL therapy, with the exception of ibrutinib within the following timeframes:
• Chemotherapy, external beam radiation therapy, anticancer antibodies within 30 days prior to the first dose of drug on this study.
• Corticosteroid use 20mg prednisone within 1 week prior to first dose on this study.
• Radio- or toxin-conjugated antibody therapy within 10 weeks prior to first dose on this study.
• Allogeneic stem cell transplant within 6 months prior to first dose on this study
• History of major surgery within 4 weeks prior to first dose on this study.
• History of prior malignancy, with the exception of adequately treated non-melanoma skin cancer, malignancies treated with curative intent and with no evidence of active disease for more than 3 years, or adequately treated cervical carcinoma in situ without current evidence of disease.
• Currently active clinically significant cardiovascular disease or history of myocardial infarction within 6 months of first dose.
• Serologic status and/or PCR testing reflecting active hepatitis B or C infection.
• Known history of infection with human immunodeficiency virus (HIV).
• Unable to swallow capsules or disease significantly affecting gastrointestinal function.

Sponsors & Collaborators

• Michael Choi: lead
• Pharmacyclics LLC.: collaborator

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Neoplasms

Interventions

ibrutinib; obinutuzumab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Michael Choi, MD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Clinical Professor

Study Record Dates

• First Submitted: November 19, 2015
• First Posted: November 23, 2015
• Study Start: June 1, 2016
• Primary Completion: November 1, 2019
• Study Completion: November 1, 2020
• Last Updated: January 25, 2019

Record last verified: 2019-01