Efficacy and Safety of Idelalisib in Combination With Bendamustine and Rituximab in Subjects With Previously Untreated Chronic Lymphocytic Leukemia

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01980888
First received: November 5, 2013
Last updated: June 24, 2016
Last verified: June 2016
  Purpose
This study will evaluate the effect of the addition of idelalisib to bendamustine and rituximab on minimal residual disease (MRD) and evaluate the progression-free survival (PFS) in participants with previously untreated chronic lymphocytic leukemia (CLL).

Condition Intervention Phase
Chronic Lymphocytic Leukemia
Drug: Idelalisib
Drug: Bendamustine
Drug: Rituximab
Drug: Placebo to match idelalisib
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Idelalisib in Combination With Bendamustine and Rituximab for Previously Untreated Chronic Lymphocytic Leukemia

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: Up to 56 months ] [ Designated as safety issue: No ]
    Progression-free survival (PFS) is defined as the interval from randomization to the first documentation of definitive disease progression or death from any cause. Definitive disease progression is CLL progression based on standard criteria, excluding lymphocytosis alone.


Secondary Outcome Measures:
  • Overall response rate [ Time Frame: Up to 56 months ] [ Designated as safety issue: No ]
    Overall response rate (ORR) is defined as the proportion of participants who achieve a confirmed complete or partial response.

  • Nodal response rate [ Time Frame: Up to 56 months ] [ Designated as safety issue: No ]
    Nodal response rate is defined as the proportion of participants who achieve a 50% decrease from baseline in the sum of the products of the greatest perpendicular diameters of index lesions.

  • Complete response rate [ Time Frame: Up to 56 months ] [ Designated as safety issue: No ]
    Complete response rate is defined as the proportion of participants who achieve a confirmed complete response.

  • Overall survival [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Overall survival is defined as the interval from randomization to death from any cause.

  • Minimal residual disease negativity rate [ Time Frame: Week 36 ] [ Designated as safety issue: No ]
    Minimal residual disease (MRD) negativity rate is defined as the proportion of participants with MRD < 10^-4 assessed by flow cytometry in bone marrow at Week 36 after therapy initiation or at least 12 weeks after the last dose of rituximab or bendamustine (whichever is later) for participants receiving the final dose of rituximab after the original scheduled date.


Enrollment: 311
Study Start Date: February 2014
Study Completion Date: June 2016
Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Idelalisib+bendamustine+rituximab
Participants will receive idelalisib for 96 weeks plus bendamustine+rituximab for 21 weeks.
Drug: Idelalisib
Idelalisib 150 mg tablet administered orally twice daily
Other Names:
  • Zydelig®
  • GS-1101
  • CAL-101
Drug: Bendamustine
Bendamustine administered intravenously at a starting dose of 90 mg/m^2. Dosing will be based on mg/m^2 of body surface area.
Drug: Rituximab
Rituximab single-use vials administered intravenously weekly starting at 375 mg/m^2 on Day 1 (Week 0) and 500 mg/m^2 thereafter
Placebo Comparator: Placebo to match idelalisib+bendamustine+rituximab
Participants will receive placebo to match idelalisib for 96 weeks plus bendamustine+rituximab for 21 weeks.
Drug: Bendamustine
Bendamustine administered intravenously at a starting dose of 90 mg/m^2. Dosing will be based on mg/m^2 of body surface area.
Drug: Rituximab
Rituximab single-use vials administered intravenously weekly starting at 375 mg/m^2 on Day 1 (Week 0) and 500 mg/m^2 thereafter
Drug: Placebo to match idelalisib
Placebo to match idelalisib administered orally twice daily

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Documented diagnosis of B-cell CLL, with diagnosis established according to International Workshop on Chronic Lymphocytic Leukemia (IWCLL)
  • No prior therapy for CLL other than corticosteroids for disease complications
  • CLL that warrants treatment
  • Presence of measurable lymphadenopathy
  • Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2

Exclusion Criteria:

  • Known histological transformation from CLL to an aggressive lymphoma (ie, Richter transformation)
  • Known presence of myelodysplastic syndrome
  • Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of randomization
  • Ongoing liver injury
  • History of non-infectious pneumonitis
  • Ongoing inflammatory bowel disease
  • History of prior allogeneic bone marrow progenitor cell or solid organ transplantation
  • Ongoing immunosuppressive therapy other than corticosteroids
  • Received last dose of study drug on another therapeutic clinical trial within 30 days prior to randomization
  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: NCT01980888

  Show 132 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Henry Adewoye, MD Gilead Sciences
  More Information

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01980888     History of Changes
Other Study ID Numbers: GS-US-312-0123  2013-003313-17 
Study First Received: November 5, 2013
Last Updated: June 24, 2016
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Bulgaria: Bulgarian Drug Agency
Canada: Health Canada
Croatia: Agency for Medicinal Product and Medical Devices
Czech Republic: State Institute for Drug Control
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute for Quality and Organizational Development in Healthcare and Medicines
Italy: The Italian Medicines Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Portugal: INFARMED, National Authority of Medicines and Health Products, IP
Romania: National Agency for Medicines and Medical Devices
Spain: Agencia Española de Medicamentos y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Idelalisib
Rituximab
Bendamustine Hydrochloride
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 24, 2016