Duvelisib and Nivolumab in Treating Patients With Richter Syndrome or Transformed Follicular Lymphoma

April 4, 2024 updated by: David Bond, MD

A Phase I Study of Duvelisib in Combination With Nivolumab for Patients With Richter's Syndrome and Transformed Follicular Lymphoma

This phase I trial studies the side effects and best dose of duvelisib when given together with nivolumab in treating patients with Richter syndrome or transformed follicular lymphoma. Duvelisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving duvelisib and nivolumab may work better in treating patients with Richter syndrome or transformed follicular lymphoma compared to giving duvelisib or nivolumab alone.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the maximum-tolerated dose (MTD) of duvelisib in combination with nivolumab for patients with Richter?s syndrome or transformed follicular lymphoma.

SECONDARY OBJECTIVES:

I. To assess preliminary efficacy of duvelisib in combination with nivolumab in Richter?s syndrome and transformed follicular lymphoma (overall response rate, progression free survival, overall survival).

II. To determine the toxicity profile of duvelisib in combination with nivolumab.

EXPLORATORY OBJECTIVES:

I. To correlate response to duvelisib in combination with nivolumab with cytogenetic/fluorescence in-situ hybridization (FISH) abnormalities of the chronic lymphocytic leukemia (CLL) and lymphoma compartments (for patients with Richter?s syndrome) at baseline.

II. To correlate response to duvelisib in combination with nivolumab with baseline deoxyribonucleic acid (DNA) mutation of CLL and lymphoma as assessed in tumor samples and cell free DNA.

III. To determine changes in T, B, and natural killer (NK) cell number and function during duvelisib plus nivolumab therapy.

OUTLINE: This is a dose-escalation study of duvelisib.

Patients receive duvelisib orally (PO) twice daily (BID) on days 1-28 and nivolumab intravenously (IV) over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months thereafter.

Study Type

Interventional

Enrollment (Actual)

7

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Ohio State University Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Diagnosis of CLL or small lymphocytic lymphoma (SLL) meeting International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria AND biopsy proven transformation to diffuse large B cell lymphoma (DLBCL), clinically consistent with Richter?s syndrome (RS) OR histologically diagnosed relapsed or refractory DLBCL including transformed follicular lymphoma (tFL) ineligible for or refractory to platinum containing salvage therapy for the dose escalation portion of the study. For the dose expansion phase only patients with CLL with transformation to DLBCL or tFL will be eligible
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Absolute neutrophil count (ANC) >= 500/uL
  • Platelet count >= 30,000/uL (unless due to bone marrow involvement)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 ULN
  • Total bilirubin =< 1.5 ULN (unless due to liver involvement, hemolysis, or Gilbert?s disease)
  • Creatinine clearance >= 40 mL/min (Cockcroft-Gault estimated)
  • Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials. Men must agree to not donate sperm during and after the study. For females, these restrictions apply for 1 month after the last dose of study drug. For males, these restrictions apply for 3 months after the last dose of study drug
  • Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [beta-hCG]) or urine pregnancy test at screening. Women who are pregnant or breastfeeding are ineligible for this study
  • Patients must sign an informed consent document indicating that they understand the purpose of and procedures required for the study, including biomarkers, and are willing to participate in the study

Exclusion Criteria:

  • Documented infection with human immunodeficiency virus (HIV) or chronic, active hepatitis B or C infection
  • Any chemotherapy or monoclonal antibodies within 14 days or kinase inhibitors (except BTKi) within 5 half-lives before cycle 1, day 1 (C1D1). BTK inhibitors may be continued until 2 days prior to C1D1. Steroids are allowed for palliation of symptoms due to lymphoma
  • Toxicity from previous therapy which has not resolved to grade 1 (or patient?s previous baseline)
  • Other active malignancies except those treated with curative intent with no active disease at the time of study entry or those felt to be at low risk of progression or recurrence over the next 2 years (such as low risk prostate cancer on active surveillance)
  • New York Heart Association (NYHA) class III/IV heart disease or other significant medical condition or organ system dysfunction which could compromise the subject?s safety or put the study outcomes at undue risk
  • Uncontrolled systemic infection
  • Unable to swallow capsules or significant malabsorption syndrome, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction at the time of screening
  • Patients who are pregnant or breastfeeding
  • Patients with known central nervous system (CNS) involvement by CLL or lymphoma
  • Patients who have underwent autologous or allogeneic stem cell transplant =< 4 weeks prior to C1D1 or have active graft-versus-host disease are excluded

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (duvelisib, nivolumab)
Patients receive duvelisib PO BID on days 1-28 and nivolumab IV over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo
Drug: Duvelisib
Given PO
Other Names:
  • IPI-145
  • 8-Chloro-2-phenyl-3-((1S)-1-(7H-purin-6-ylamino)ethyl)isoquinolin-1(2H)-one
  • INK-1197

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum-tolerated dose (MTD) of duvelisib
Time Frame: Up to 28 days
The MTD is defined as the highest dose level where at most one patient out of six experiences dose-limiting toxicities.
Up to 28 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall response rate
Time Frame: Up to 3 years
Will be defined as the proportion of patients achieving a complete or partial response; any eligible patient who begins treatment with the combination regimen will be included in the denominator. Will be calculated with a 95% binomial confidence interval.
Up to 3 years
Progression-free survival (PFS)
Time Frame: From cycle 1, day 1 to date of progression or death, assessed up to 3 years
The method of Kaplan Meier will be used to estimate PFS.
From cycle 1, day 1 to date of progression or death, assessed up to 3 years
Overall survival (OS)
Time Frame: From cycle 1, day 1 to date of progression or death, assessed up to 3 years
The method of Kaplan Meier will be used to estimate OS.
From cycle 1, day 1 to date of progression or death, assessed up to 3 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response to duvelisib in combination with nivolumab
Time Frame: Baseline
Will be correlated with cytogenetic/fluorescence in-situ hybridization abnormalities of the chronic lymphocytic leukemia (CLL) and lymphoma compartments (for patients with Richter syndrome). The chi-squared test and logistic regression will be utilized to evaluate the association.
Baseline
Response to duvelisib in combination with nivolumab
Time Frame: Baseline
Will be correlated with deoxyribonucleic acid (DNA) mutation of CLL and lymphoma and assessed in tumor samples and cell free DNA. The chi-squared test and logistic regression will be utilized to evaluate the association.
Baseline
Changes in T, B, and NK cell number and function
Time Frame: Up to 3 years
Will be summarized using graphical method in a descriptive manner and tested using nonparametric Wilcoxon signed-rank test due to small sample size.
Up to 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

David Bond, MD

Investigators

  • Principal Investigator: David Bond, MD, Ohio State University Comprehensive Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 5, 2019

Primary Completion (Actual)

February 14, 2024

Study Completion (Actual)

February 14, 2024

Study Registration Dates

First Submitted

March 25, 2019

First Submitted That Met QC Criteria

March 25, 2019

First Posted (Actual)

March 27, 2019

Study Record Updates

Last Update Posted (Actual)

April 8, 2024

Last Update Submitted That Met QC Criteria

April 4, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OSU-18173
  • NCI-2019-01028 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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