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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Recruitment Status : Terminated (withdrawn by sponsor)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

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 Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Idelalisib (GS-1101)-Associated Colitis - Molecular and Cellular Mechanisms Research Proposal
Actual Study Start Date : February 1, 2016
Actual Primary Completion Date : June 5, 2018
Actual Study Completion Date : June 5, 2018


Arm Intervention/treatment
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.
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




Primary Outcome Measures :
  1. 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 ]
  2. 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 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02928510


Locations
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United States, California
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, United States, 90095
Sponsors and Collaborators
Jonsson Comprehensive Cancer Center
Gilead Sciences
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Daniel Hommes UCLA / Jonsson Comprehensive Cancer Center

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Responsible Party: Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT02928510     History of Changes
Other Study ID Numbers: 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 )
First Posted: October 10, 2016    Key Record Dates
Last Update Posted: February 28, 2019
Last Verified: February 2019

Additional relevant MeSH terms:
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Idelalisib
Lymphoma
Leukemia
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, B-Cell
Signs and Symptoms
Signs and Symptoms, Digestive
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action