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Mechanisms of Idelalisib-Associated Diarrhea in Patients With Relapsed Chronic Lymphocytic Leukemia, Indolent Non-hodgkin Lymphoma, or Small Lymphocytic Lymphoma

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ClinicalTrials.gov Identifier: NCT02928510
Recruitment Status : Terminated (withdrawn by sponsor)
First Posted : October 10, 2016
Last Update Posted : February 28, 2019
Sponsor:
Collaborators:
Gilead Sciences
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Jonsson Comprehensive Cancer Center

Tracking Information
First Submitted Date  ICMJE August 12, 2016
First Posted Date  ICMJE October 10, 2016
Last Update Posted Date February 28, 2019
Actual Study Start Date  ICMJE February 1, 2016
Actual Primary Completion Date June 5, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 6, 2016)
  • Cellular mechanisms of idelalisib-induced diarrhea/colitis assessed by a number of tests in order to provide variability in comparisons for the units of measure. [ Time Frame: Up to 11 years ]
  • The Mechanism of Action (MOA) of idelalisib will be assessed with a number of tests in order to provide variability in comparisons for the units of measure. [ Time Frame: Up to 11 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02928510 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Mechanisms of Idelalisib-Associated Diarrhea in Patients With Relapsed Chronic Lymphocytic Leukemia, Indolent Non-hodgkin Lymphoma, or Small Lymphocytic Lymphoma
Official Title  ICMJE Idelalisib (GS-1101)-Associated Colitis - Molecular and Cellular Mechanisms Research Proposal
Brief Summary This research trial studies the mechanisms of idelalisib-associated diarrhea in patients with chronic lymphocytic leukemia, indolent non-hodgkin lymphoma, or small lymphocytic lymphoma that has come back after a period of improvement. The cancer treatment drug idelalisib triggers diarrhea in some patients. Studying stool, blood, and tissue samples in the lab from patients who are given idelalisib may help doctors learn more about the side effects and may help to treat them in future patients.
Detailed Description

PRIMARY OBJECTIVES:

I. To explore the cellular and molecular mechanisms of idelalisib-induced diarrhea/colitis in relapsed chronic lymphocytic leukemia (CLL), relapsed indolent non-hodgkin lymphomas (iNHL), or relapsed small lymphocytic lymphoma (SLL).

II. To further understand the mechanism of action (MOA) of idelalisib in context of the nodal microenvironment and the possible involvement of the immune system in idelalisib's anti-lymphoma activity.

OUTLINE:

Patients receive a physical examination during visit 1. A stool sample, blood sample, and 6 biopsies are collected at visit 2, and patients undergo a flexible fiberoptic sigmoidoscopy. Patients receive idelalisib orally (PO) twice daily (BID) after visit 2. Treatment continues in the absence of disease progression or unacceptable toxicity. A third research visit occurs upon development of idelalisib-associated diarrhea/colitis symptoms. Patients with diarrhea/colitis symptoms undergo a full colonoscopy and collection of stool and blood samples. Control patients with no diarrhea/colitis symptoms undergo all needed tests and assessments including a flexible fiberoptic sigmoidoscopy and collection of stool and blood samples. All patients undergo optional biospecimen collection at the time of disease progression.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE
  • Absence of Signs or Symptoms
  • B-Cell Non-Hodgkin Lymphoma
  • Digestive System Signs and Symptoms
  • Indolent Adult Non-Hodgkin Lymphoma
  • Recurrent B-Cell Non-Hodgkin Lymphoma
  • Recurrent Chronic Lymphocytic Leukemia
  • Recurrent Indolent Adult Non-Hodgkin Lymphoma
  • Recurrent Small Lymphocytic Lymphoma
Intervention  ICMJE
  • Procedure: Biospecimen Collection
    Undergo biospecimen collection
  • Procedure: Colonoscopy
    Undergo colonoscopy
  • Procedure: Colposcopic Biopsy
    Undergo colposcopic biopsy
  • Drug: Idelalisib
    Given PO
    Other Names:
    • CAL-101
    • GS-1101
    • Phosphoinositide-3 Kinase Delta Inhibitor CAL-101
    • Zydelig
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Other: Pharmacological Study
    Correlative studies
  • Procedure: Physical Examination
    Undergo physical examination
    Other Names:
    • Assessment
    • Physical
    • Physical Assessment
    • PHYSICAL EXAM
  • Procedure: Sigmoidoscopy
    Undergo sigmoidoscopy
    Other Name: Proctosigmoidoscopy
Study Arms  ICMJE Experimental: Basic Science (biospecimen collection, idelalisib)
Patients receive a physical examination during visit 1. A stool sample, blood sample, and 6 biopsies are collected at visit 2, and patients undergo a flexible fiberoptic sigmoidoscopy. Patients receive idelalisib PO twice daily BID after visit 2. Treatment continues in the absence of disease progression or unacceptable toxicity. A third research visit occurs upon development of idelalisib-associated diarrhea/colitis symptoms. Patients with diarrhea/colitis symptoms undergo a full colonoscopy and collection of stool and blood samples. Control patients with no diarrhea/colitis symptoms undergo all needed tests and assessments including a flexible fiberoptic sigmoidoscopy and collection of stool and blood samples. All patients undergo optional biospecimen collection at the time of disease progression.
Interventions:
  • Procedure: Biospecimen Collection
  • Procedure: Colonoscopy
  • Procedure: Colposcopic Biopsy
  • Drug: Idelalisib
  • Other: Laboratory Biomarker Analysis
  • Other: Pharmacological Study
  • Procedure: Physical Examination
  • Procedure: Sigmoidoscopy
Publications * Not Provided

*   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 Terminated
Actual Enrollment  ICMJE
 (submitted: February 26, 2019)
1
Original Estimated Enrollment  ICMJE
 (submitted: October 6, 2016)
30
Actual Study Completion Date  ICMJE June 5, 2018
Actual Primary Completion Date June 5, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Food and Drug Administration (FDA)-approved indications for idelalisib of relapsed, histologically confirmed B-cell indolent non-hodgkin lymphoma (iNHL) or chronic lymphocytic leukemia (CLL)
  • For iNHL: measureable nodal disease, defined as the presence of >= 1 nodal lesion that measures >= 2 cm in a single dimension as assessed by computed tomography (CT) or magnetic resonance imaging (MRI)
  • Discontinuation of all other therapies (including radiotherapy or chemotherapy) for the treatment of iNHL >= 3 weeks before initiation of study treatment
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  • Absolute neutrophil count > 750
  • Platelets > 50,000
  • Total bilirubin < 2 X institutional upper limit of normal (ULN)
  • Aspartate transaminase (AST) serum glutamic-oxaloacetic transaminase (SGOT)/ alanine transferase (ALT) serum glutamate pyruvate transaminase (SPGT) < 3 X institutional ULN
  • Creatinine < 2 X institutional ULN
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent; all patients must have signed, witnessed informed consent prior to registration

Exclusion Criteria:

  • Prior exposure to idelalisib
  • Known histological transformation from iNHL to diffuse large B-cell lymphoma or Richter's Transformation for CLL
  • Ongoing treatment with any other investigational agents
  • Known central nervous system (CNS) involvement of lymphoma (CNS staging not required)
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to idelalisib
  • Uncontrolled inter-current illnesses including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Known human immunodeficiency virus (HIV) infection (HIV testing not required)
  • Known John Cunningham (JC) virus infection and/or progressive multifocal leukoencephalopathy (PML)
  • Clinically active hepatitis A, B, or C infections
  • NOTE: Patients with chronic hepatitis C virus (HCV) or hepatitis B virus (HBV) infection may enroll if other laboratory criteria are met; those with HBV surface antigen positivity may enroll only if maintained on appropriate suppressive antiviral therapy for the duration of enrollment in the trial
  • Pregnancy or active nursing of an infant
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 NCT02928510
Other Study ID Numbers  ICMJE 15-001217
NCI-2016-01002 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
15-001217 ( Other Identifier: UCLA / Jonsson Comprehensive Cancer Center )
P30CA016042 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jonsson Comprehensive Cancer Center
Study Sponsor  ICMJE Jonsson Comprehensive Cancer Center
Collaborators  ICMJE
  • Gilead Sciences
  • National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Daniel Hommes UCLA / Jonsson Comprehensive Cancer Center
PRS Account Jonsson Comprehensive Cancer Center
Verification Date February 2019

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