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

NCT03892044 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: OSU-18173NCI-2019-01028
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Chronic Lymphocytic Leukemia; Recurrent Diffuse Large B-Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Richter Syndrome; Small Lymphocytic Lymphoma; Transformed Chronic Lymphocytic Leukemia to Diffuse Large B-Cell Lymphoma; Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma; Transformed Small Lymphocytic Lymphoma to Diffuse Large B-Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Maximum-tolerated dose (MTD) of duvelisib

  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 Outcomes (3)

• Overall response rate

  Up to 3 years

• Progression-free survival (PFS)

  From cycle 1, day 1 to date of progression or death, assessed up to 3 years

• Overall survival (OS)

  From cycle 1, day 1 to date of progression or death, assessed up to 3 years

Other Outcomes (3)

• Response to duvelisib in combination with nivolumab

  Baseline

• Response to duvelisib in combination with nivolumab

  Baseline

• Changes in T, B, and NK cell number and function

  Up to 3 years

Study Arms (1)

Treatment (duvelisib, nivolumab)

EXPERIMENTAL

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.

Drug: Duvelisib; Biological: Nivolumab

Interventions

Duvelisib DRUG

Given PO

Also known as: 8-Chloro-2-phenyl-3-((1S)-1-(7H-purin-6-ylamino)ethyl)isoquinolin-1(2H)-one, INK-1197, IPI-145

Treatment (duvelisib, nivolumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Treatment (duvelisib, nivolumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• David Bond, MD: lead

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Publications (1)

• Iannello A, Vitale N, Coma S, Arruga F, Chadburn A, Di Napoli A, Laudanna C, Allan JN, Furman RR, Pachter JA, Deaglio S, Vaisitti T. Synergistic efficacy of the dual PI3K-delta/gamma inhibitor duvelisib with the Bcl-2 inhibitor venetoclax in Richter syndrome PDX models. Blood. 2021 Jun 17;137(24):3378-3389. doi: 10.1182/blood.2020010187.

  PMID: 33786583 DERIVED

Related Links

• The Jamesline

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Large B-Cell, Diffuse

Interventions

duvelisib; Nivolumab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• David Bond, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 25, 2019
• First Posted: March 27, 2019
• Study Start: November 5, 2019
• Primary Completion: February 14, 2024
• Study Completion: February 14, 2024
• Last Updated: May 2, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)