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

Sponsor

Jonsson Comprehensive Cancer Center (Other)

Overall Status

Terminated

CT.gov ID

NCT02928510

Collaborator

Gilead Sciences (Industry)

Enrollment

Location

28.1

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
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	Procedure: Biospecimen Collection Procedure: Colonoscopy Procedure: Colposcopic Biopsy Drug: Idelalisib Other: Laboratory Biomarker Analysis Other: Pharmacological Study Procedure: Physical Examination Procedure: Sigmoidoscopy

Detailed Description

PRIMARY OBJECTIVES:

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).
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 Design

Study Type:

Observational

Actual Enrollment :

1 participants

Observational Model:

Case-Only

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Feb 1, 2016

Actual Primary Completion Date :

Jun 5, 2018

Actual Study Completion Date :

Jun 5, 2018

Arms and Interventions

Arm	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.	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 Names: Proctosigmoidoscopy

Arm

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.

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 Names:

Proctosigmoidoscopy

Outcome Measures

Primary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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