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

NCT ID: NCT02928510

Last Updated: 2021-07-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Total Enrollment

1 participants

Study Classification

OBSERVATIONAL

Study Start Date

2016-02-01

Study Completion Date

2018-06-05

Brief Summary

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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

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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.

Conditions

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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

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

PROSPECTIVE

Study Groups

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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.

Biospecimen Collection

Intervention Type PROCEDURE

Undergo biospecimen collection

Colonoscopy

Intervention Type PROCEDURE

Undergo colonoscopy

Colposcopic Biopsy

Intervention Type PROCEDURE

Undergo colposcopic biopsy

Idelalisib

Intervention Type DRUG

Given PO

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Pharmacological Study

Intervention Type OTHER

Correlative studies

Physical Examination

Intervention Type PROCEDURE

Undergo physical examination

Sigmoidoscopy

Intervention Type PROCEDURE

Undergo sigmoidoscopy

Interventions

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Biospecimen Collection

Undergo biospecimen collection

Intervention Type PROCEDURE

Colonoscopy

Undergo colonoscopy

Intervention Type PROCEDURE

Colposcopic Biopsy

Undergo colposcopic biopsy

Intervention Type PROCEDURE

Idelalisib

Given PO

Intervention Type DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Pharmacological Study

Correlative studies

Intervention Type OTHER

Physical Examination

Undergo physical examination

Intervention Type PROCEDURE

Sigmoidoscopy

Undergo sigmoidoscopy

Intervention Type PROCEDURE

Other Intervention Names

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CAL-101 GS-1101 Phosphoinositide-3 Kinase Delta Inhibitor CAL-101 Zydelig Assessment Physical Physical Assessment PHYSICAL EXAM Proctosigmoidoscopy

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role collaborator

Jonsson Comprehensive Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Daniel Hommes

Role: PRINCIPAL_INVESTIGATOR

UCLA / Jonsson Comprehensive Cancer Center

Locations

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UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

Countries

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United States

Other Identifiers

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NCI-2016-01002

Identifier Type: REGISTRY

Identifier Source: secondary_id

15-001217

Identifier Type: OTHER

Identifier Source: secondary_id

15-001217

Identifier Type: -

Identifier Source: org_study_id

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