Clinical Trials /

Duvelisib Maintenance After Autologous Stem Cell Transplant in T-Cell and Indolent B-Cell Lymphomas

NCT04331119

Description:

The investigators hypothesize that duvelisib maintenance after autologous stem cell transplant with carmustine, etoposide, cytarabine, and melphalan (BEAM) conditioning in patients with T-cell lymphomas, or a history of indolent B-cell lymphomas, will be safe and well tolerated, and will improve progression free survival.

Related Conditions:
  • Indolent Non-Hodgkin Lymphoma
  • T-Cell Non-Hodgkin Lymphoma
  • Transformed Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Duvelisib Maintenance After Autologous Stem Cell Transplant in T-Cell and Indolent B-Cell Lymphomas
  • Official Title: Phase II Trial With Safety Lead in of Duvelisib Maintenance After Autologous Stem Cell Transplant in T-Cell and Indolent B-Cell Lymphomas

Clinical Trial IDs

  • ORG STUDY ID: 20-x104
  • NCT ID: NCT04331119

Conditions

  • T-Cell Lymphoma
  • Indolent B-Cell Lymphoma

Interventions

DrugSynonymsArms
DuvelisibCopiktraDuvelisib Maintenance

Purpose

The investigators hypothesize that duvelisib maintenance after autologous stem cell transplant with carmustine, etoposide, cytarabine, and melphalan (BEAM) conditioning in patients with T-cell lymphomas, or a history of indolent B-cell lymphomas, will be safe and well tolerated, and will improve progression free survival.

Trial Arms

NameTypeDescriptionInterventions
Duvelisib MaintenanceExperimental-Patients who received the standard BEAM regimen with autologous hematopoietic stem cells transplant will begin duvelisib maintenance at 25 mg PO BID after count recovery (approximately 30 days after transplant) for one year. If the patient is in a complete remission at day +100, with no evidence of disease on PET/CT, then the dosing schedule of duvelisib may be changed to 25 mg BID for 14 days, then 14 days off in 28 day cycles (at the treating physician's discretion). If the patient has residual disease, duvelisib will continue at 25 mg BID until they have a negative PET CT. PET CTs will be completed every 3 months for patients with residual disease. Duvelisib maintenance will be continued for one year post-transplant.
  • Duvelisib

Eligibility Criteria

        Inclusion Criteria:

          -  Diagnosis of T cell non-Hodgkin lymphoma, or indolent B cell non-Hodgkin lymphoma
             (e.g., follicular, CLL/SLL, lymphoplasmacytic, or marginal zone) including transformed
             to aggressive lymphoma.

          -  Eligible for autologous stem cell transplantation as determined by the treating
             physician or completed BEAM autologous transplant within the last 30 days.

          -  At least 18 years of age at time of enrollment

          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

          -  Adequate organ function as defined below:

               -  Serum creatinine ≤ 1.5 times institutional upper limit of normal (IULN)

               -  Total bilirubin ≤ 1.5 x IULN. Patients with Gilbert's Syndrome may have a
                  bilirubin > 1.5 x IULN

               -  Hemoglobin ≥ 8.0 g/dL

               -  Absolute neutrophil count ≥ 1.0 x 109/L

               -  Platelet count ≥ 75 x 109/L

               -  AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN

          -  Women of childbearing potential and men must agree to use highly effective
             contraception prior to study entry and for the duration of study participation and for
             3 months after the last dose of duvelisib. Negative serum β human chorionic
             gonadotropin (βHCG) pregnancy test within 7 days before first treatment is required if
             the patient is a woman of childbearing potential.

          -  Participants or a participant's legally authorized representative must be able to
             understand and willing to sign an IRB approved written informed consent document

        Exclusion Criteria:

          -  Currently receiving any other experimental therapy or has received experimental
             therapy within 4 weeks prior to study treatment

          -  History of allergic reaction attributed to compounds of similar chemical or biologic
             composition to duvelisib or other agents used in the study.

          -  Prior history of drug-induced colitis or drug-induced pneumonitis

          -  History of concurrent interstitial lung disease or severely impaired lung function

          -  History of chronic liver disease or veno-occlusive disease

          -  History of tuberculosis within 2 years prior to enrollment

          -  Administration of a live or live attenuated vaccine within 6 weeks of first duvelisib
             dose

          -  Ongoing treatment with chronic immunosuppressants (e.g., cyclosporine) or systemic
             steroids > 20 mg of prednisone (or equivalent) per day

          -  Ongoing treatment for systemic bacterial, fungal, or viral infections at screening.

        Note: patients on antimicrobial, antifungal, or antiviral prophylaxis are not specifically
        excluded is all other inclusion/exclusion criteria are met

          -  Unable to receive prophylactic treatment for pneumocystis, herpes simplex virus (HSV),
             or herpes zoster (VZV) at screening

          -  Infection with HBV, HCV. Subjects with a positive HBsAg or HCV Ab on pre-transplant
             infection screening will be excluded. Subjects with a positive HBcAb must have
             negative HBV DNA to be eligible and must be periodically monitored for HBV
             reactivation by institutional guidelines.

          -  Baseline QTcF > 500 milliseconds. This does not apply to subjects with right or left
             bundle branch blocks

          -  Concurrent active malignancy other than non-melanoma skin cancer or carcinoma in situ
             of the cervix, bladder cancer, or prostate cancer not requiring treatment.

          -  Clinically significant medical condition of malabsorption, inflammatory bowel disease,
             chronic conditions which manifest with diarrhea, refractory nausea,vomiting, or any
             other condition that will interfere significantly with drug absorption

          -  Concurrent administration of medications or foods that are strong inhibitors or
             inducers of cytochrome P450 3A (CYP3A). No prior use within 2 weeks before the start
             of study intervention.

          -  Active cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection (i.e., subjects
             with detectable viral load)

          -  History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia
             requiring medication or a pacemaker within the last 6 months prior to screening.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, or unstable
             cardiac arrhythmia.

          -  Pregnant or breastfeeding.

          -  Patients with HIV are eligible unless their CD4+ T-cell counts are < 350 cells/mcL or
             they have a history of AIDS-defining opportunistic infection within the 12 months
             prior to registration. Concurrent treatment with effective ART according to DHHS
             treatment guidelines is recommended. Recommend exclusion of specific ART agents based
             on predicted drug-drug interactions (i.e. concurrent strong CYP3A4 inhibitors
             (ritonavir and cobicistat) or inducers (efavirenz) are contraindicated).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:2 years
Safety Issue:
Description:The PFS time will be calculated as the duration of time from autologous stem cell transplant (day 0) to the date of earliest progression or death, whichever occurs first.

Secondary Outcome Measures

Measure:Safety and tolerabilty as measured by number of study treatment related adverse events
Time Frame:From start of treatment through 30 days after last dose of duvelisib (estimated to be 13 months)
Safety Issue:
Description:-Adverse events will be assessed using CTCAE v5.0 criteria
Measure:Safety and tolerabilty as measured by discontinuations due to treatment-related adverse events
Time Frame:From start of treatment through 30 days after last dose of duvelisib (estimated to be 13 months)
Safety Issue:
Description:
Measure:Overall response rate (ORR)
Time Frame:100 days after transplant
Safety Issue:
Description:-Defined as the percentage of patients with a confirmed complete or partial response, monitored with PET/CT scans.
Measure:Overall survival (OS)
Time Frame:2 years
Safety Issue:
Description:-Defined as the duration of time from the date of first dose of study treatment to death from any cause. Patients who are alive by the data cutoff date will be censored at the last follow up.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Washington University School of Medicine

Last Updated

March 30, 2020