Clinical Trials /

Study of IPI-145 in Combination With Rituximab or Bendamustine/Rituximab in Hematologic Malignancies

NCT01871675

Description:

The goal of this study is to characterize the safety, maximum tolerated dose (MTD) and preliminary efficacy profile of IPI-145 given in combination with rituximab, or bendamustine plus rituximab, to subjects with select relapsed/refractory hematologic malignancies.

Related Conditions:
  • Chronic Lymphocytic Leukemia
  • Non-Hodgkin Lymphoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Study of IPI-145 in Combination With <span class="go-doc-concept go-doc-intervention">Rituximab</span> or <span class="go-doc-concept go-doc-intervention">Bendamustine</span>/<span class="go-doc-concept go-doc-intervention">Rituximab</span> in Hematologic Malignancies

Title

  • Brief Title: Study of IPI-145 in Combination With Rituximab or Bendamustine/Rituximab in Hematologic Malignancies
  • Official Title: An Open-label, Phase Ib Study of IPI-145 in Combination With Rituximab or Bendamustine/Rituximab in Select Subjects With Lymphoma or Chronic Lymphocytic Leukemia
  • Clinical Trial IDs

    NCT ID: NCT01871675

    ORG ID: SCRI HEMREF 34

    Trial Conditions

    Lymphoma

    Chronic Lymphocytic Leukemia

    Non-Hodgkin Lymphoma

    T-cell Lymphoma

    Trial Interventions

    Drug Synonyms Arms
    IPI-145 Duvelisib Arm 1: IPI-145 plus Rituximab, Arm 2: IPI-145 plus Rituximab/Bendamustine
    Rituximab Rituxan Arm 1: IPI-145 plus Rituximab, Arm 2: IPI-145 plus Rituximab/Bendamustine
    Bendamustine Treanda Arm 2: IPI-145 plus Rituximab/Bendamustine

    Trial Purpose

    The goal of this study is to characterize the safety, maximum tolerated dose (MTD) and
    preliminary efficacy profile of IPI-145 given in combination with rituximab, or bendamustine
    plus rituximab, to subjects with select relapsed/refractory hematologic malignancies.

    Detailed Description

    This trial consists of two parallel arms. For each treatment arm, a 3+3 dose escalation
    design will be applied in 3-6 subject cohorts until the maximum tolerated dose of IPI-145
    when given with rituximab (Arm 1) or in combination with rituximab and bendamustine (Arm 2)
    is determined. Treatment arm selection will be chosen by the investigator and will depend on
    the agents previously administered to the subject. Once the MTD has been determined, the
    arms will move on to a dose expansion phase. During the dose expansion phase, each treatment
    arm will enroll to population specific cohorts to assess efficacy. All subjects must have
    had at least one prior anticancer treatment. The dose expansion cohorts are:

    Arm 1: Cohort A - CLL: Cohort B - CD20+ NHL

    Arm 2: Cohort A - CLL: Cohort B - CD20+ NHL

    Trial Arms

    Name Type Description Interventions
    Arm 1: IPI-145 plus Rituximab Experimental IPI-145 will be administered orally, twice daily, in 28-day (4-week) cycles, on a continuous basis at the maximum tolerated dose of 25 mg twice-daily (BID), as determined in the dose escalation phase. A maximum of 12 cycles of IPI-145 will be administered. Rituximab 375 mg/m2 will be administered intravenously (IV) beginning on Day 1 once weekly during a 28 day cycle; 2 cycles of rituximab will be administered. IPI-145, Rituximab
    Arm 2: IPI-145 plus Rituximab/Bendamustine Experimental IPI-145 will be administered orally, twice daily, in 28 day cycles, on a continuous basis, until disease progression, unacceptable toxicity or patient refusal. The maximum tolerated dose of IPI-145 will be 25 mg twice-daily (BID) as determined in the dose escalation phase. A maximum of 12 cycles of IPI-145 will be administered. Rituximab 375 mg/m2 will be administered intravenously (IV) beginning on Day 1 once weekly of each 28 day cycle. A maximum of 6 cycles of rituximab will be given. Bendamustine 90 mg/m2 IV will be administered on Days 1 and 2, of each 28 day cycle. Rituximab should be administered prior to bendamustine. IPI-145, Rituximab, Bendamustine

    Eligibility Criteria

    Inclusion Criteria:

    1. Dose Escalation Phase

    Arm 1 and Arm 2: Limited to subjects diagnosed with low grade CD-20 positive B-Cell
    NHL with at least one prior anticancer treatment.

    2. Dose Expansion Phase

    Arm 1 Cohort A: Limited to subjects with CD-20 positive CLL with at least one prior
    anticancer treatment.

    Arm 1 Cohort B: Limited to subjects with diagnosis of CD-20 positive NHL with at
    least one prior anticancer treatment.

    Arm 2 Cohort A: Limited to subjects with CD-20 positive CLL with at least one prior
    anticancer treatment.

    Arm 2 Cohort B: Limited to subjects with diagnosis of CD-20 positive NHL with at
    least one prior anticancer treatment.

    3. Disease status requirement:

    - CLL subjects: symptomatic disease that mandate treatment;

    - Indolent NHL subjects: symptomatic disease requiring treatment according to the
    clinical judgment of the investigator;

    - Other lymphoma subjects: disease requiring treatment according to the judgment
    of the investigator.

    4. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 2.

    5. Subject must have measurable disease using the disease-specific response criteria for
    NHL or CLL

    6. Age 18 years.

    7. Subject has recovered from all clinically significant toxicities related to prior
    antineoplastic therapies with the exception of alopecia and bone marrow and organ
    functions.

    8. Adequate organ system function 2 weeks prior to Day 1, defined as follows:

    - Absolute neutrophil count (ANC) 1.0 x 109/L unless related to underlying CLL or
    indolent NHL bone marrow involvement, and then ANC 500 x 109/L permitted.

    - Platelets 100 x 109/L unless related to underlying CLL or indolent NHL bone
    marrow involvement, and then platelets 75 x 109/L permitted.

    - Subjects receiving IPI-145 plus rituximab with bone marrow involvement may
    enroll with platelets 40 x 109/L.

    - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 1.5 x ULN
    and total bilirubin 1.5 times the upper limit of normal (ULN) (except for
    subjects with Gilbert's disease)

    - Serum creatinine 1.5 x ULN

    9. Life expectancy of 12 weeks.

    10. Women of child-bearing potential (WCBP) must have a negative serum or urine pregnancy
    test.

    11. Ability to understand the nature of this study and give written informed consent.

    Exclusion Criteria:

    1. Prior allogeneic hematopoietic stem cell transplant (HSCT).

    2. Prior autologous transplant or radioimmunotherapy 6 months prior to the first dose
    of trial treatment.

    3. Subject has a high grade lymphoma such as Burkitt's, lymphoblastic or small
    non-cleaved cell lymphomas. Subjects with intermediate grade lymphoma (such as
    diffuse large B-cell lymphoma) are eligible.

    4. Subjects with diffuse B-cell lymphoma must either not be eligible for autologous bone
    marrow transplant (BMT) or relapsed after autologous BMT.

    5. More than three previous cytotoxic chemotherapy regimens for subjects treated on the
    arm containing bendamustine.

    6. Subjects who have had a severe allergic or anaphylactic reaction to any humanized or
    murine monoclonal antibodies.

    7. Chemotherapy, cancer immunosuppressive therapy, growth factors (except
    erythropoietin), radiation therapy (other than whole brain irradiation [WBI]) surgery
    or ablative therapy or investigational drugs/devices 28 days before first dose of
    trial treatment.

    8. Subjects receiving high doses of corticosteroids must have been tapered to a stable
    dose at least 7 days before the first dose of trial treatment.

    9. Tyrosine kinase inhibitor within 7 days prior to the first dose of trial treatment.

    10. Subjects with overt leptomeningeal leukemia or central nervous system (CNS) lymphoma.
    Subjects must be free of CNS disease for a minimum of 2 months. Subjects with
    symptoms of CNS disease must have a negative diagnostic lumbar puncture prior to
    study enrollment.

    11. Subjects with a history of stroke, unstable angina, myocardial infarction, or
    ventricular arrhythmia requiring medication or mechanical control within the last 6
    months.

    12. Baseline QTcF >480 ms. Note: This criterion does not apply to subjects with a left
    bundle branch block.

    13. Subjects who have had a venous thromboembolic event requiring anticoagulation and who
    meet any of the following criteria:

    - Have been on a stable dose of anticoagulation for <1 month.

    - Have had a Grade 2, 3 or 4 hemorrhages in the last 30 days.

    - Are experiencing continued symptoms for their venous thromboembolic event.

    14. Subjects with a history of liver disease as a result of alcohol abuse, chronic
    hepatitis, or other chronic liver disease (other than metastatic disease to the
    liver).

    15. Subjects with positive HBsAg, HBcAb or HCV are excluded.

    16. Subjects with a history of tuberculosis within the preceding two years.

    17. Prior surgery affecting drug absorption or any gastrointestinal dysfunction that
    could alter drug absorption.

    18. Subjects with a known hypersensitivity to bendamustine or rituximab.

    19. Presence of active infection within 72 hours of treatment. Subjects with ongoing use
    of prophylactic antibiotics are eligible as long as there is no evidence of active
    infection and the antibiotic is not included on the list of prohibited medications.

    20. Known diagnosis of human immunodeficiency virus (HIV).

    21. Concurrent administration of medications or foods that are strong or moderate
    inhibitors or inducers of CYP3A.

    22. Women who are pregnant or lactating.

    23. Psychological, familial, sociological, or geographical conditions that do not permit
    compliance with the protocol.

    24. Concurrent condition that in the investigator's opinion would jeopardize compliance
    with the protocol or would impart excessive risk associated with study participation
    that would make it inappropriate for the subject to be enrolled.

    25. Inability or unwillingness to comply with study and/or follow-up procedures outlined
    in the protocol.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    The number of adverse events, serious adverse events, and dose limiting toxicities as a measure of safety and tolerability

    Secondary Outcome Measures

    Antitumor activity

    Trial Keywords

    Lymphoma

    Chronic Lymphocytic Leukemia

    Non-Hodgkin Lymphoma

    T-cell Lymphoma

    Rituxan

    Bendamustine

    Hematologic Malignancy

    Relapsed

    Refractory