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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01088048
First received: March 12, 2010
Last updated: May 11, 2015
Last verified: May 2015
  Purpose

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).


Condition Intervention Phase
Indolent Non-Hodgkin's Lymphoma
Chronic Lymphocytic Leukemia
Mantle Cell Lymphoma
Drug: Idelalisib
Drug: Rituximab
Drug: Bendamustine
Drug: Ofatumumab
Drug: Fludarabine
Drug: Everolimus
Drug: Bortezomib
Drug: Chlorambucil
Drug: Lenalidomide
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Extent of exposure to idelalisib and toxicity [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Extent of exposure to idelalisib and toxicity will be assessed by incidence and severity of adverse events.


Secondary Outcome Measures:
  • Clinical Response Rate [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Plasma concentrations of everolimus [ Time Frame: Predose and 1.5 hour postdose ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    This endpoint will only be evaluated for participants in the Idelalisib + Rituximab + Lenalidomide group.


Enrollment: 241
Study Start Date: April 2010
Study Completion Date: April 2015
Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Idelalisib + Rituximab
Idelalisib 100 mg or 150 mg twice daily + rituximab 375 mg/m^2 for 8 weekly doses
Drug: Idelalisib
Idelalisib tablet administered orally
Other Names:
  • GS-1101
  • CAL-101
  • Zydelig®
Drug: Rituximab
Rituximab administered intravenously
Other Name: Rituxan
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.
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
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.
Drug: Idelalisib
Idelalisib tablet administered orally
Other Names:
  • GS-1101
  • CAL-101
  • Zydelig®
Drug: Bendamustine
Bendamustine administered intravenously
Other Name: Treanda
Experimental: Idelalisib + Ofatumumab
Idelalisib 150 mg twice daily + 12 doses of ofatumumab over the course of 6 months. For participants with CLL only.
Drug: Idelalisib
Idelalisib tablet administered orally
Other Names:
  • GS-1101
  • CAL-101
  • Zydelig®
Drug: Ofatumumab
Ofatumumab administered intravenously
Other Name: Arzerra
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.
Drug: Idelalisib
Idelalisib tablet administered orally
Other Names:
  • GS-1101
  • CAL-101
  • Zydelig®
Drug: Fludarabine
Fludarabine administered orally
Other Name: Fludara
Experimental: Idelalisib + Everolimus
Idelalisib 150 mg twice daily + oral everolimus 10 mg once daily. For participants with MCL only.
Drug: Idelalisib
Idelalisib tablet administered orally
Other Names:
  • GS-1101
  • CAL-101
  • Zydelig®
Drug: Everolimus
Everolimus administered orally twice daily until disease progression
Other Names:
  • Afinitor
  • RAD-001
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.
Drug: Idelalisib
Idelalisib tablet administered orally
Other Names:
  • GS-1101
  • CAL-101
  • Zydelig®
Drug: Bortezomib
Bortezomib administered as a subcutaneous injection
Other Names:
  • Velcade
  • codenamed PS-341
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.
Drug: Idelalisib
Idelalisib tablet administered orally
Other Names:
  • GS-1101
  • CAL-101
  • Zydelig®
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
Experimental: Idelalisib + Rituximab + Chlorambucil
Idelalisib 150 mg twice daily + rituximab 375 mg/m^2 + chlorambucil 10 mg/m^2 for participants with CLL only.
Drug: Idelalisib
Idelalisib tablet administered orally
Other Names:
  • GS-1101
  • CAL-101
  • Zydelig®
Drug: Rituximab
Rituximab administered intravenously
Other Name: Rituxan
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
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)
Drug: Idelalisib
Idelalisib tablet administered orally
Other Names:
  • GS-1101
  • CAL-101
  • Zydelig®
Drug: Rituximab
Rituximab administered intravenously
Other Name: Rituxan
Drug: Lenalidomide
Lenalidomide administered orally
Other Name: Revlimid

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01088048

Locations
United States, Alabama
Clearview Cancer Institute
Huntsville, Alabama, United States, 35805
United States, California
UCLA
Los Angeles, California, United States, 90024
Stanford Cancer Center
Palo Alto, California, United States, 94304-5548
United States, Maryland
Center for Cancer and Blood Disorders
Bethesda, Maryland, United States, 20817
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, New York
Long Island Jewish Medical Center
New Hyde Park, New York, United States, 11040
Weill Medical College of Cornell
New York, New York, United States, 10021
United States, Oregon
Willamette Valley Cancer Institute and Research Center
Springfield, Oregon, United States, 97477
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
United States, Texas
MD Anderson Cancer
Houston, Texas, United States, 77030
United States, Washington
North Star Lodge Cancer Center
Yakima, Washington, United States, 98902
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Thomas Jahn, MD Gilead Sciences
  More Information

No publications provided by Gilead Sciences

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01088048     History of Changes
Other Study ID Numbers: 101-07
Study First Received: March 12, 2010
Last Updated: May 11, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
CLL
non-Hodgkin lymphoma (NHL)
mantle cell lymphoma (MCL)
phosphatidylinositol 3-kinase
bendamustine
CD20 mAb
rituximab
CAL-101
Ofatumumab
indolent non-Hodgkin lymphoma (iNHL)
fludarabine
everolimus
bortezomib
chlorambucil
lenalidomide

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma
Lymphoma, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, Non-Hodgkin
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Antineoplastic Agents
Bendamustine
Bortezomib
Chlorambucil
Everolimus
Fludarabine
Fludarabine phosphate
Immunologic Factors
Lenalidomide
Nitrogen Mustard Compounds
Rituximab
Sirolimus
Alkylating Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on July 30, 2015