Clinical Trials /

Safety and Efficacy of Tenalisib (RP6530) in Combination With Romidepsin in Patients With Relapsed/Refractory T-cell Lymphoma

NCT03770000

Description:

To characterize safety, tolerability and to establish the maximum tolerated dose (MTD) of Tenalisib in combination with Romidepsin in patients with R/R T-cell lymphoma.

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

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Safety and Efficacy of Tenalisib (RP6530) in Combination With Romidepsin in Patients With Relapsed/Refractory T-cell Lymphoma
  • Official Title: An Open Label, Phase I/II Study to Evaluate the Safety and Efficacy of Tenalisib (RP6530), a Novel PI3K δ/γ Dual Inhibitor Given in Combination With a Histone Deacetylase (HDAC) Inhibitor, Romidepsin in Adult Patients With Relapsed/Refractory T-cell Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: RP6530+Romidepsin-1805
  • NCT ID: NCT03770000

Conditions

  • T Cell Lymphoma

Interventions

DrugSynonymsArms
TenalisibRP6530Tenalisib+Romidepsin
RomidepsinTenalisib+Romidepsin

Purpose

To characterize safety, tolerability and to establish the maximum tolerated dose (MTD) of Tenalisib in combination with Romidepsin in patients with R/R T-cell lymphoma.

Trial Arms

NameTypeDescriptionInterventions
Tenalisib+RomidepsinExperimentalParticipants receive Tenalisib in escalating doses daily Orally BID and Romidepsin in escalating doses intravenously on day 1, 8 and 15
  • Tenalisib
  • Romidepsin

Eligibility Criteria

        Inclusion Criteria:

          1. Pathologically confirmed T-cell lymphomas at the enrolling institution.

          2. Disease status as defined as relapsed or progressed patients who have received at
             least one systemic therapy.

          3. The patients should have received NOT more than three prior systemic combination
             chemotherapies

          4. PTCL patients must have measurable disease defined as at least one bidimensional
             measurable lesion with minimum measurement of > 1.5 cm in the longest diameter.

          5. Must have ECOG performance status ≤ 2

          6. Adequate bone marrow, liver and renal function in line with below mentioned laboratory
             requirements.

               1. Hemoglobin ≥8.0 g/dL

               2. Absolute neutrophil count (ANC) ≥1,000/µL

               3. Platelet count ≥75,000/μL

               4. Total bilirubin ≤1.5 times the ULN (or ≤3 x ULN, if patient has Gilbert syndrome)

               5. AST (SGOT) and ALT (SGPT) ≤ 3 x ULN; ≤ 5 ULN in case of liver involvement

               6. Calculated creatinine clearance (CrCl) > 50 ml/min by Cockcroft-Gault formula

          7. Use of an effective means of contraception for women of childbearing potential and men
             with partners of childbearing potential.

          8. Provide written informed consent prior to any study-specific screening procedures.

          9. Willingness and capability to comply with the requirements of the study

        Exclusion Criteria:

          1. Patient receiving anticancer therapy including any investigational therapy ≤3 weeks or
             5 half-lives (whichever is shorter) prior to C1D1.

          2. Patient who discontinued prior therapy with PI3K inhibitors or HDAC inhibitors due to
             drug toxicity.

          3. PTCL patients with Allo-SCT on active GVHD or immunosuppression therapy within 3
             months prior to C1D1. CTCL patients with the history of Allo-SCT will be excluded.

          4. Patient with medical conditions requiring the use of systemic immunosuppressive
             medications (> 20 mg/day of prednisone or equivalent).

          5. Severe bacterial, viral or mycotic infection requiring systemic treatment.

          6. Known seropositive requiring anti-viral therapy for human immunodeficiency virus (HIV)
             infection.

          7. Known seropositive requiring anti-viral therapy for hepatitis B virus (HBV) infection
             OR evidence of active hepatitis B infection as defined by detectable viral load if the
             antibody tests are positive..

          8. Known seropositive requiring anti-viral therapy for hepatitis c virus (HCV) infection
             OR patients with positive hepatitis C virus Ab.

          9. Subjects with active EBV unrelated to underlying lymphoma (positive serology for anti-
             EBV VCA IgM antibody and negative for anti-EBV EBNA IgG antibody, or clinical
             manifestations and positive EBV PCR consistent with active EBV infection.

         10. Subject with active CMV (positive serology for anti-CMV IgM antibody and negative for
             anti-CMV IgG antibody and positive CMV PCR with clinical manifestations consistent
             with active CMV infection) and requiring therapy.

         11. Uncontrolled or significant cardiovascular disease including, but not limited to:

               -  Congenital long QT syndrome.

               -  QTcF interval > 450 msec

               -  Myocardial infarction or stroke/TIA within the past 6 months

               -  Uncontrolled angina within the past 3 months

               -  Significant ECG abnormalities including 2nd degree atrio- ventricular (AV) block
                  (AV) block type II, 3rd degree AV block.

               -  History of clinically significant arrhythmias (such as ventricular tachycardia,
                  ventricular fibrillation or torsades de pointes),

               -  History of other clinically significant heart disease (ie, cardiomyopathy,
                  congestive heart failure with NYHA functional classification III-IV,
                  pericarditis, significant pericardial effusion)

               -  Requirement for daily supplemental oxygen therapy.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose (MTD) of Tenalisib in combination with Romidepsin in Patients with T cell lymphoma
Time Frame:28 days
Safety Issue:
Description:The MTD was defined as the highest dose level at which no more than 1 in 6 participants experienced a dose-limiting toxicity (DLT) during the first 28-day cycle of treatment

Secondary Outcome Measures

Measure:Overall response rate (ORR) with Tenalisib and Romidepsin combination
Time Frame:12 weeks
Safety Issue:
Description:No. of patients with partial and complete response
Measure:Duration of Response (DoR) with Tenalisib and Romidepsin combination
Time Frame:12 weeks
Safety Issue:
Description:The time period from the response achieved in patient until the disease progression
Measure:Maximum observed plasma concentration (Cmax)
Time Frame:8 days
Safety Issue:
Description:Assessment of Cmax in subjects treated with Tenalisib and Romidepsin combination

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Rhizen Pharmaceuticals SA

Trial Keywords

  • T cell Lymphoma
  • RP6530
  • Tenalisib
  • Romidepsin

Last Updated

November 26, 2019