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

Idelalisib (GS-1101)-Associated Colitis - Molecular and Cellular Mechanisms Research Proposal

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.

Study Overview

• Status: Terminated
• Conditions: B-Cell Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Indolent Adult Non-Hodgkin Lymphoma; Absence of Signs or Symptoms; Digestive System Signs and Symptoms; Indolent Adult Non-Hodgkin Lymphoma
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Procedure: Colonoscopy; Procedure: Sigmoidoscopy; Procedure: Biospecimen Collection; Drug: Idelalisib; Procedure: Colposcopic Biopsy; Procedure: Physical Examination

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: Observational
• Enrollment (Actual): 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA / Jonsson Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients suffering from relapsed chronic lymphocytic leukemia (CLL), relapsed indolent Non-Hodgkin lymphomas (iNHL), or relapsed small lymphocytic lymphoma (SLL) will be enrolled in the UCLA Lymphoma Program and they will be receiving Idelalisib/Zydelig as the standard care treatment are potentially eligible for this specimen collection study.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

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.

Other: Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacological Study; Correlative studies; Procedure: Colonoscopy; Undergo colonoscopy; Procedure: Sigmoidoscopy; Undergo sigmoidoscopy; Other Names: Proctosigmoidoscopy; Procedure: Biospecimen Collection; Undergo biospecimen collection; Drug: Idelalisib; Given PO; Other Names: GS-1101; CAL-101; Zydelig; Phosphoinositide-3 Kinase Delta Inhibitor CAL-101; Procedure: Colposcopic Biopsy; Undergo colposcopic biopsy; Procedure: Physical Examination; Undergo physical examination; Other Names: Assessment; Physical; Physical Assessment; PHYSICAL EXAM

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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.	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.	Up to 11 years

Collaborators and Investigators

• Sponsor: Jonsson Comprehensive Cancer Center
• Collaborators: Gilead Sciences
• Investigators: Principal Investigator: Daniel Hommes, UCLA / Jonsson Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2016
• Primary Completion (Actual): June 5, 2018
• Study Completion (Actual): June 5, 2018

Study Registration Dates

• First Submitted: August 12, 2016
• First Submitted That Met QC Criteria: October 6, 2016
• First Posted (Estimate): October 10, 2016

Study Record Updates

• Last Update Posted (Actual): July 14, 2021
• Last Update Submitted That Met QC Criteria: July 12, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease Attributes; Leukemia, B-Cell; Lymphoma; Lymphoma, B-Cell; Leukemia; Recurrence; Lymphoma, Non-Hodgkin; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Signs and Symptoms, Digestive; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Idelalisib
• Other Study ID Numbers: 15-001217 (Other Identifier: UCLA / Jonsson Comprehensive Cancer Center); NCI-2016-01002 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No