Clinical Trials /

A Phase 2 Study Comparing 2 Intermittent Dosing Schedules of Duvelisib in Subjects With Indolent Non-Hodgkin Lymphoma. (TEMPO)

NCT04038359

Description:

This study will examine the effects of predefined 2 week duvelisib dose holidays on tumor responses and safety/tolerability.

Related Conditions:
  • Indolent Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Phase 2 Study Comparing 2 Intermittent Dosing Schedules of Duvelisib in Subjects With Indolent Non-Hodgkin Lymphoma. (TEMPO)
  • Official Title: A Phase 2, Randomized, Open-label, 2-Arm Study Comparing 2 Intermittent Dosing Schedules of Duvelisib in Subjects With Indolent Non Hodgkin Lymphoma (iNHL) (TEMPO)

Clinical Trial IDs

  • ORG STUDY ID: VS-0145-229
  • NCT ID: NCT04038359

Conditions

  • Indolent Non-hodgkin Lymphoma

Interventions

DrugSynonymsArms
DuvelisibCopiktra, VS-0145Duvelisib, Continuous and Intermittent Dosing

Purpose

This study will examine the effects of predefined 2 week duvelisib dose holidays on tumor responses and safety/tolerability.

Detailed Description

      This is a Phase 2, randomized, open-label, 2 arm study designed to evaluate the efficacy and
      safety of prescribed drug holidays of duvelisib treatment in subjects with R/R iNHL who have
      received at least 1 prior systemic therapy.
    

Trial Arms

NameTypeDescriptionInterventions
Duvelisib, Continuous and Intermittent DosingExperimentalDuvelisib 25 mg BID continuously for 10 weeks, followed by 25 mg BID dosed two weeks on and two weeks off of each subsequent 4-week cycles.
  • Duvelisib
Duvelisib, Intermittent DosingExperimentalDuvelisib 25 mg BID dosed two weeks on and two weeks off.
  • Duvelisib

Eligibility Criteria

        Inclusion Criteria:

          -  Age ≥ 18 years, ECOG performance status ≤ 2

          -  Histologically confirmed diagnosis of iNHL (Subtypes include FL Grades 1 to 3a,
             marginal zone lymphoma (splenic, nodal, or extranodal), or SLL

          -  Must have received 1 prior systemic regimen for iNHL

          -  Must have documented radiologic evidence of disease progression, and at least 1
             bi-dimensionally measurable lesion ≥ 1.5 cm (which has not been previously
             irradiated), according to 2007 revised IWG criteria

          -  Must have adequate organ function defined by the following laboratory parameters:

               -  Absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L

               -  Platelet count ≥ 75 × 10^9/L

               -  Serum creatinine < 2.0 mg/dL (197 µmol/L)

               -  Total bilirubin ≤ 1.5 × upper limit of normal (ULN) (exception: subjects with
                  Gilbert's Syndrome may have a bilirubin > 1.5 × ULN)

               -  Aspartate transaminase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) and
                  alanine aminotransferase (ALT)/serum pyruvic transaminase (SGPT) ≤ 3.0 × ULN

        Exclusion Criteria:

          -  Anticancer treatment, major surgery, or use of any investigational drug within 28 days
             before the start of study intervention; palliative radiation therapy is allowed if > 7
             days and any toxicity is Grade ≤ 1

          -  Clinical or histological evidence of transformation to a more aggressive subtype of
             lymphoma or grade 3b FL or Richters' transformation or CLL

          -  Prior allogeneic hematopoietic stem cell transplant (HSCT); treatment with a PI3K
             inhibitor

          -  History of drug-induced colitis or pneumonitis; TB treatment ≤ 2 years prior to
             randomization; administration of a live or live attenuated vaccine within 6 weeks of
             randomization

          -  Ongoing treatment with chronic immunosuppressants or systemic steroids or treatment
             for systemic bacterial, fungal, or viral infection

          -  Active cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection

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

          -  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.

          -  Baseline QTcF > 500 ms

          -  Concurrent active malignancy other than non-melanoma skin cancer or carcinoma in situ
             of the cervix, bladder cancer, or prostate cancer not requiring treatment. Subjects
             with previous malignancies are eligible if they have been disease-free for 2 years or
             more.

          -  Unstable or severe uncontrolled medical condition that would, in the Investigator's
             judgment, increase the subject's risk to participating in this study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:ORR (Objective Response Rate)
Time Frame:36 months
Safety Issue:
Description:Proportion of subjects achieving a CR or PR will be estimated as per IWG Criteria.

Secondary Outcome Measures

Measure:PFS (Progression Free Survival)
Time Frame:5 years
Safety Issue:
Description:From time of first dose of study intervention to PD or death.
Measure:ORR (Objective Response Rate)
Time Frame:ORR estimated at 6, 12, 18, and 24 months after first dose of study intervention.
Safety Issue:
Description:Proportion of subjects achieving a CR or PR will be estimated as per Lugano Criteria
Measure:DOR (Duration of Response)
Time Frame:5 years
Safety Issue:
Description:From the time of first response to PD using KM methods.
Measure:OS (Overall Survival)
Time Frame:5 years
Safety Issue:
Description:From time of first dose of study intervention to death.
Measure:LNRR (Lymph Node Response Rate)
Time Frame:36 months
Safety Issue:
Description:LNRR will be calculated as the proportion of subjects achieving ≥ 50% decrease in the SPD of target lymph nodes.
Measure:TTFR (Time To First Relapse)
Time Frame:36 months
Safety Issue:
Description:From the time of first dose of study intervention to time of first CR or PR.
Measure:Number of participants with treatment-emergent adverse events as assessed by CTCAE v5.0
Time Frame:36 months
Safety Issue:
Description:From the time of screening to the end of Safety Follow-Up period of the study.
Measure:Peak Plasma Concentration (Cmax)
Time Frame:36 months
Safety Issue:
Description:
Measure:TTF (Time To Treatment Failure)
Time Frame:5 years
Safety Issue:
Description:From first dose of study intervention until discontinuation for any reason and will be summarized using KM methods.
Measure:Area under the plasma concentration versus time curve (AUC)
Time Frame:36 months
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Verastem, Inc.

Trial Keywords

  • PI3K Inhibitor

Last Updated

January 3, 2020