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

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

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.

Study Overview

• Status: Completed
• Conditions: T Cell Lymphoma
• Intervention / Treatment: Drug: Tenalisib; Drug: Romidepsin

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • USC/Norris Comprehensive Cancer Center
    • San Francisco, California, United States, 94143
      • University of California, Hellen Diller Family Comprehensive Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami-Sylvester Comprehensive Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute of Emory University
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Cancer Center
  • Kansas
    • Fairway, Kansas, United States, 66205
      • The University of Kansas Cancer Center
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Norton Cancer Institute, St Matthews Campus
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center, Hackensack University Medical Center
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Comprehensive Cancer Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Institute
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Tennessee
    • Nashville, Tennessee, United States, 37232-5505
      • Vanderbilt Ingram Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center,

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tenalisib+Romidepsin; Participants receive Tenalisib in escalating doses daily Orally BID and Romidepsin in escalating doses intravenously on day 1, 8 and 15	Drug: Tenalisib; Tenalisib, BID orally daily; Other Names: RP6530; Drug: Romidepsin; Romidepsin IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With and Without Dose Limiting Toxicities (DLTs)	The DLTs will be classified according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR) With Tenalisib and Romidepsin Combination	Overall response (ORR) = CR + PR) was assessed according to the Lugano classification with PTCL and according to the modified Severity Weighted Assessment Tool (mSWAT)/Global assessment in patients with CTCL.	12 weeks
Duration of Response (DoR) With Tenalisib and Romidepsin Combination	The time period from the response achieved in patient until the disease progression	28 weeks
Maximum Observed Plasma Concentration (Cmax)	Assessment of Cmax in subjects treated with Tenalisib and Romidepsin combination. Blood samples for measurement of RP6530 plasma concentrations were collected pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 10, and 11 hours after dosing on Day 8 of the first cycle. Maximum (peak) drug concentration (Cmax in nanograms/milliliter) was estimated using Single-Dose data.	8 days

Collaborators and Investigators

• Sponsor: Rhizen Pharmaceuticals SA

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2019
• Primary Completion (Actual): May 14, 2021
• Study Completion (Actual): May 14, 2021

Study Registration Dates

• First Submitted: December 6, 2018
• First Submitted That Met QC Criteria: December 6, 2018
• First Posted (Actual): December 10, 2018

Study Record Updates

• Last Update Posted (Actual): October 28, 2022
• Last Update Submitted That Met QC Criteria: October 27, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Tenalisib; RP6530; Romidepsin; T cell Lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antibiotics, Antineoplastic; Phosphoinositide-3 Kinase Inhibitors; Romidepsin; Tenalisib
• Other Study ID Numbers: RP6530+Romidepsin-1805

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No