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Study to Investigate Idelalisib in Combination With Chemotherapeutic Agents, Immunomodulatory Agents and Anti-CD20 Monoclonal Antibody (mAb) in Subjects With Relapsed or Refractory Indolent B-cell Non-Hodgkin's Lymphoma, Mantle Cell Lymphoma or Chronic Lymphocytic Leukemia

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ClinicalTrials.gov Identifier: NCT01088048
Recruitment Status : Completed
First Posted : March 17, 2010
Last Update Posted : October 23, 2018
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE March 12, 2010
First Posted Date  ICMJE March 17, 2010
Last Update Posted Date October 23, 2018
Study Start Date  ICMJE April 2010
Actual Primary Completion Date April 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 24, 2015)
Extent of exposure to idelalisib and toxicity [ Time Frame: Up to 1 year ]
Extent of exposure to idelalisib and toxicity will be assessed by incidence and severity of adverse events.
Original Primary Outcome Measures  ICMJE
 (submitted: March 15, 2010)
Safety of CAL-101 in combination with rituximab and bendamustine - assessed by adverse events, vital signs, clinical laboratory tests and ECG [ Time Frame: One year ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 24, 2015)
  • Clinical Response Rate [ Time Frame: Up to 1 year ]
    Clinical activity will be evaluated by clinical response rate, assessed by CT scan, clinical laboratory tests, and bone marrow biopsy if indicated.
  • Plasma concentrations of idelalisib [ Time Frame: Predose and 1.5 hour postdose ]
  • Plasma concentrations of chemotherapeutic agents in a select subset of participants [ Time Frame: For idelalisib: predose and 0.5, 1, 1.5, 2, 3, 4, and 6 hours postdose; For bendamustine: Predose and 15, 30, 45, 60, 75, 90, 120, 180, 240, 300, and 360 minutes postdose ]
  • Plasma concentrations of everolimus [ Time Frame: Predose and 1.5 hour postdose ]
    This endpoint will only be evaluated for participants in the Idelalisib + Everolimus group.
  • Plasma concentration of lenalidomide [ Time Frame: Predose and 1.5 hour postdose ]
    This endpoint will only be evaluated for participants in the Idelalisib + Rituximab + Lenalidomide group.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 15, 2010)
  • Clinical activity will be evaluated by clinical response rate - assessed by CT scan, clincal laboratory tests and bone marrow biopsy if indicated [ Time Frame: Every 2-3 months ]
  • Measure plasma concentrations of CAL-101
  • Measure plasma concentrations of bendamustine in a select subset of patients
  • To investigate the pharmacodynamic effects of CAL-101 treatment - assessed by comparing pre and post dose blood samples
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Investigate Idelalisib in Combination With Chemotherapeutic Agents, Immunomodulatory Agents and Anti-CD20 Monoclonal Antibody (mAb) in Subjects With Relapsed or Refractory Indolent B-cell Non-Hodgkin's Lymphoma, Mantle Cell Lymphoma or Chronic Lymphocytic Leukemia
Official Title  ICMJE A Phase I Study to Investigate the Safety and Clinical Activity of Idelalisib in Combination With Chemotherapeutic Agents, Immunomodulatory Agents and Anti-CD20 mAb in Subjects With Relapsed or Refractory Indolent B-cell Non-Hodgkin Lymphoma, Mantle Cell Lymphoma or Chronic Lymphocytic Leukemia
Brief Summary This study will evaluate the safety and clinical activity of idelalisib in combination with an anti-CD20 monoclonal antibody (mAb), a chemotherapeutic agent, an mTOR inhibitor, a protease inhibitor, an antiangiogenic agent, and/or an immunomodulatory agent in participants with relapsed or refractory indolent B-cell non-Hodgkin lymphoma (NHL), mantle cell lymphoma (MCL), or chronic lymphocytic leukemia (CLL).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Indolent Non-Hodgkin's Lymphoma
  • Chronic Lymphocytic Leukemia
  • Mantle Cell Lymphoma
Intervention  ICMJE
  • Drug: Idelalisib
    Idelalisib tablet administered orally
    Other Names:
    • GS-1101
    • CAL-101
    • Zydelig®
  • Drug: Rituximab
    Rituximab administered intravenously
    Other Name: Rituxan
  • Drug: Bendamustine
    Bendamustine administered intravenously
    Other Name: Treanda
  • Drug: Ofatumumab
    Ofatumumab administered intravenously
    Other Name: Arzerra
  • Drug: Fludarabine
    Fludarabine administered orally
    Other Name: Fludara
  • Drug: Everolimus
    Everolimus administered orally twice daily until disease progression
    Other Names:
    • Afinitor
    • RAD-001
  • Drug: Bortezomib
    Bortezomib administered as a subcutaneous injection
    Other Names:
    • Velcade
    • codenamed PS-341
  • Drug: Chlorambucil
    Chlorambucil administered on Days 1-7 every 28 days to allow appropriate therapy for participants with CLL and to coordinate into a cycle period equivalent to other study treatment regimens.
    Other Name: Leukeran
  • Drug: Lenalidomide
    Lenalidomide administered orally
    Other Name: Revlimid
Study Arms  ICMJE
  • Experimental: Idelalisib + Rituximab
    Idelalisib 100 mg or 150 mg twice daily + rituximab 375 mg/m^2 for 8 weekly doses
    Interventions:
    • Drug: Idelalisib
    • Drug: Rituximab
  • Experimental: Idelalisib + Rituximab + Bendamustine
    Idelalisib 150 mg twice daily + rituximab 375 mg/m^2 on Day 1 + bendamustine 90 mg/m^2 on Days 1 & 2 of Cycles 1-6 for participants with iNHL or MCL. Bendamustine 70 mg/m^2 for for participants with CLL only.
    Interventions:
    • Drug: Idelalisib
    • Drug: Rituximab
    • Drug: Bendamustine
  • Experimental: Idelalisib + Bendamustine
    Idelalisib 100 mg or 150 mg twice daily + bendamustine 90 mg/m^2 or 70 mg/m^2 on Days 1 & 2 of Cycles 1-6.
    Interventions:
    • Drug: Idelalisib
    • Drug: Bendamustine
  • Experimental: Idelalisib + Ofatumumab
    Idelalisib 150 mg twice daily + 12 doses of ofatumumab over the course of 6 months. For participants with CLL only.
    Interventions:
    • Drug: Idelalisib
    • Drug: Ofatumumab
  • Experimental: Idelalisib + Fludarabine
    Idelalisib 150 mg twice daily + oral fludarabine 40 mg/m^2 on Days 1-5 of Cycles 1-6. For participants with CLL only.
    Interventions:
    • Drug: Idelalisib
    • Drug: Fludarabine
  • Experimental: Idelalisib + Everolimus
    Idelalisib 150 mg twice daily + oral everolimus 10 mg once daily. For participants with MCL only.
    Interventions:
    • Drug: Idelalisib
    • Drug: Everolimus
  • Experimental: Idelalisib + Bortezomib
    Idelalisib 150 mg twice daily + bortezomib 1.3 mg/m^2 once weekly for 3 weeks (Days 1, 8, and 15) followed by a 13-day rest period. For participants with MCL only.
    Interventions:
    • Drug: Idelalisib
    • Drug: Bortezomib
  • Experimental: Idelalisib + Chlorambucil
    Idelalisib 150 mg twice daily + chlorambucil 10 mg/m^2 on Days 1-7 every 28 days. For participants with CLL only.
    Interventions:
    • Drug: Idelalisib
    • Drug: Chlorambucil
  • Experimental: Idelalisib + Rituximab + Chlorambucil
    Idelalisib 150 mg twice daily + rituximab 375 mg/m^2 + chlorambucil 10 mg/m^2 for participants with CLL only.
    Interventions:
    • Drug: Idelalisib
    • Drug: Rituximab
    • Drug: Chlorambucil
  • Experimental: Idelalisib + Rituximab + Lenalidomide
    Idelalisib 150 mg twice daily + rituximab 375 mg/m^2 + lenalidomide 5, 10 or 20 mg (M.D. Anderson Cancer Center only)
    Interventions:
    • Drug: Idelalisib
    • Drug: Rituximab
    • Drug: Lenalidomide
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 24, 2015)
241
Original Estimated Enrollment  ICMJE
 (submitted: March 15, 2010)
36
Actual Study Completion Date  ICMJE April 2015
Actual Primary Completion Date April 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age ≥ 18
  • Previously treated with relapsed or refractory disease (refractory defined as not responding to a standard regimen or progressing within 6 months of the last course of a standard regimen)
  • Disease status requirement:

    • For CLL patients, symptomatic disease that mandates treatment as defined by the International Workshop on Chronic Lymphocytic Lymphoma (IWCLL) 2008 criteria
    • For indolent NHL and MCL patients, measurable disease by CT scan defined as at least 1 lesion that measures > 2 cm in a single dimension
  • WHO performance status of ≤ 2
  • For men and women of child-bearing potential, willing to use adequate contraception (ie, latex condom, cervical cap, diaphragm, abstinence, etc.) for the entire duration of the study.

    • For Cohort 7 only: Women of child bearing potential must have 2 negative pregnancy tests prior to starting Lenalidomide.
  • Able to provide written informed consent

Exclusion Criteria:

  • Is not a good candidate to receive any of the drugs administered in the study for a given disease (idelalisib, bendamustine, rituximab, ofatumumab, fludarabine, everolimus, bortezomib, or chlorambucil), according to the clinical judgment of the investigator
  • Patients with atypical immunophenotype with t(11:14) translocation or cyclin D1 over‑expression (CLL patients only)
  • Had radiotherapy, radioimmunotherapy, biological therapy, chemotherapy, or treatment with an investigational product within 4-weeks prior to the baseline disease status tests
  • Had treatment with a short course of corticosteroids for symptom relief within 1‑week prior to the baseline disease status tests
  • Has had an allogeneic hematopoietic stem cell transplant
  • Has known active central nervous system involvement of the malignancy
  • Is pregnant or nursing
  • Has active, serious infection requiring systemic therapy. Patients may receive prophylactic antibiotics and antiviral therapy at the discretion of the investigator
  • Has absolute neutrophil count (ANC) < 1000/µL, unless it is related to underlying CLL, MCL or indolent NHL, the latter documented by > 50% infiltration of bone marrow by tumor cells
  • Has platelet count < 75000/µL, unless it is related to underlying CLL, MCL, or iNHL, the latter documented by > 50% infiltration of bone marrow by tumor cells
  • Has serum creatinine ≥ 2.0 mg/dL

    • For Cohort 7 only: Has creatinine clearance < 60 mL/min
  • Has serum bilirubin ≥ 2 mg/dL (unless due to Gilbert's syndrome) for patients with iNHL or CLL; for patients with MCL, serum bilirubin ≥ 1.5 x upper limit of normal
  • Has serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≥ 2 x upper limit of normal
  • Has Child-Pugh Class B or C hepatic impairment
  • Has a positive test for HIV antibodies
  • Has active hepatitis B or C (confirmed by RNA test). Patients with serologic evidence of prior exposure are eligible.
  • Prior treatment with idelalisib
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01088048
Other Study ID Numbers  ICMJE 101-07
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Time Frame: 18 months after study completion
Access Criteria: A secured external environment with username, password, and RSA code.
URL: http://www.gilead.com/research/disclosure-and-transparency
Responsible Party Gilead Sciences
Study Sponsor  ICMJE Gilead Sciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Thomas Jahn, MD Gilead Sciences
PRS Account Gilead Sciences
Verification Date May 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP