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Completed

NCT Number: NCT01088048

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

The primary objective of the study is to evaluate the safety of idelalisib in combination with an anti-CD20 monoclonal antibody (mAb), a chemotherapeutic agent, a mammalian target of rapamycin (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).

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Key information

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key 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

Key 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

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Treatment and study plan

idelalisib

Drug

Idelalisib tablet administered orally

Other names: GS-1101, CAL-101, Zydelig®

Rituximab

Drug

Rituximab administered intravenously

Other names: Rituxan

Bendamustine

Drug

Bendamustine administered intravenously

Other names: Treanda

ofatumumab

Drug

Ofatumumab administered intravenously

Other names: Arzerra

Fludarabine

Drug

Fludarabine administered orally

Other names: Fludara

Everolimus

Drug

Everolimus administered orally twice daily until disease progression

Other names: Afinitor, RAD-001

bortezomib

Drug

Bortezomib administered as a subcutaneous injection

Other names: Velcade, codenamed PS-341

Chlorambucil

Drug

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 names: Leukeran

Lenalidomide

Drug

Lenalidomide administered orally

Other names: Revlimid

Primary outcomes

  1. Duration of Exposure to IDELA

    Time frame: First dose date up to 12 months

    Duration of exposure to IDELA was summarized using descriptive statistics.

  2. Toxicity of Administration of IDELA

    Time frame: First dose date up to 5 years

    Percentage of participants experiencing toxicities of administration of IDELA were measured according to the Common Terminology Criteria for Adverse Events v4.02

Secondary outcomes

  1. Overall Response Rate

    Time frame: Up to 5 years

    Overall Response Rate (ORR) was defined as the percentage of participants achieving a complete response (CR) or partial response (PR).

    The response definitions were based on the following standard criteria established for each indication:

    • CLL: International Workshop on chronic lymphocytic leukemia (IWCLL),2008
    • iNHL & MCL: Cheson, 2007
  2. Duration of Response

    Time frame: Up to 5 years

    Duration of response (DOR) was defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of disease progression or death from any cause.

  3. Time to Response

    Time frame: Up to 5 years

    Time to response (TTR) was defined as the interval from the start of study drug to the first documentation of CR or PR.

  4. Progression-free Survival

    Time frame: Up to 5 years

    Progression free survival (PFS) was defined as the interval from the start of study drug to the earlier of the first documentation of disease progression or death from any cause.

    The response definitions were based on the following standard criteria established for each indication:

    • CLL: International Workshop on chronic lymphocytic leukemia (IWCLL), 2008
    • iNHL & MCL: Cheson, 2007
  5. Overall Survival

    Time frame: Up to 5 years

    Overall Survival (OS) was defined as the interval from the start of study drug to death from any cause.

  6. Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5)

    Time frame: Predose, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0 hours postdose at Week 0; predose, 1.5 hours postdose at Weeks 4, 12, and 24

  7. Plasma Concentration of IDELA (Cohort 4)

    Time frame: Predose at Week 0; predose, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0 hours postdose at Week 4; predose, 1.5 hours postdose at Week 12; and predose, 1.5 hours postdose at Week 24

  8. Plasma Concentration of IDELA (Cohort 6)

    Time frame: Predose, 1.5 hours postdose at Weeks 0, 4, 12 and 24

  9. Plasma Concentration of IDELA (Cohort 7)

    Time frame: Predose, 1.5 hours postdose at Weeks 0, 5 and 13

  10. Sub-study: Plasma Concentration of IDELA (Cohorts 1-4)

    Time frame: pre dose and 0.5, 1, 1.5, 2.0, 3.0, 4.0, and 6.0 hours post dose

  11. Plasma Concentration of Bendamustine

    Time frame: Predose, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0 hours postdose at Week 0

  12. Plasma Concentration of Everolimus

    Time frame: Predose, 1.5 hours postdose at Weeks 0 and 4

  13. Plasma Concentration of Lenalidomide

    Time frame: Predose, 1.5 hours postdose at Week 1 and predose at Week 5

Sponsors and collaborators

Lead sponsor

Gilead Sciences

Industry

Registry information

Official study 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

Important dates

Study start
2010
Primary completion
2015
Study completion
2015
First posted
Mar 17, 2010
Registry last updated
Mar 18, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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