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

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Brief Title

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

Official Title

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

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.
    

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 Phase

Phase 1

Study Type

Interventional


Primary Outcome

Maximum-tolerated dose (MTD) of duvelisib

Secondary Outcome

 Overall response rate

Condition

Chronic Lymphocytic Leukemia

Intervention

Duvelisib

Study Arms / Comparison Groups

 Treatment (duvelisib, nivolumab)
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

44

Start Date

November 5, 2019

Completion Date

December 31, 2022

Primary Completion Date

December 31, 2021

Eligibility Criteria

        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
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Jennifer A Woyach, MD, 1-800-293-5066, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT03892044

Organization ID

OSU-18173

Secondary IDs

NCI-2019-01028

Responsible Party

Sponsor-Investigator

Study Sponsor

David Bond, MD

Collaborators

 National Cancer Institute (NCI)

Study Sponsor

Jennifer A Woyach, MD, Principal Investigator, Ohio State University Comprehensive Cancer Center


Verification Date

January 2021