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

• ClinicalTrials.gov Identifier: NCT03770000
• Recruitment Status: Active, not recruiting
• First Posted: December 10, 2018
• Last Update Posted: November 10, 2020
• Sponsor: Rhizen Pharmaceuticals SA
• Information provided by (Responsible Party): Rhizen Pharmaceuticals SA

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
T Cell Lymphoma	Drug: Tenalisib; Drug: Romidepsin	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 42 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: March 12, 2019
• Estimated Primary Completion Date: December 2020
• Estimated Study Completion Date: November 2021

Arms and Interventions

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 Name: RP6530; Drug: Romidepsin; Romidepsin IV

Outcome Measures

Primary Outcome Measures :

1. Maximum tolerated dose (MTD) of Tenalisib in combination with Romidepsin in Patients with T cell lymphoma [ Time Frame: 28 days ]
   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 :

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

Eligibility Criteria

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

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.

Contacts and Locations

Locations

United States, California

USC/Norris Comprehensive Cancer Center

Los Angeles, California, United States, 90033

University of California, Hellen Diller Family Comprehensive Cancer Center

San Francisco, California, United States, 94143

United States, Colorado

University of Colorado Cancer Center

Aurora, Colorado, United States, 80045

United States, Florida

University of Miami-Sylvester Comprehensive Cancer Center

Miami, Florida, United States, 33136

United States, Georgia

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States, 30322

United States, Illinois

Rush University Cancer Center

Chicago, Illinois, United States, 60612

United States, Kansas

The University of Kansas Cancer Center

Fairway, Kansas, United States, 66205

United States, Kentucky

Norton Cancer Institute, St Matthews Campus

Louisville, Kentucky, United States, 40207

United States, Michigan

University of Michigan

Ann Arbor, Michigan, United States, 48109

United States, New Jersey

John Theurer Cancer Center, Hackensack University Medical Center

Hackensack, New Jersey, United States, 07601

United States, New York

Roswell Park Comprehensive Cancer Center

Buffalo, New York, United States, 14263

United States, Ohio

Cleveland Clinic Taussig Cancer Institute

Cleveland, Ohio, United States, 44195

United States, Oregon

Oregon Health & Science University

Portland, Oregon, United States, 97239

United States, Tennessee

Vanderbilt Ingram Cancer Center

Nashville, Tennessee, United States, 37232-5505

United States, Texas

The University of Texas MD Anderson Cancer Center,

Houston, Texas, United States, 77030

Sponsors and Collaborators

Rhizen Pharmaceuticals SA

More Information

• Responsible Party: Rhizen Pharmaceuticals SA
• ClinicalTrials.gov Identifier: NCT03770000
• Other Study ID Numbers: RP6530+Romidepsin-1805
• First Posted: December 10, 2018
• Last Update Posted: November 10, 2020
• Last Verified: November 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Rhizen Pharmaceuticals SA:

T cell Lymphoma; RP6530; Tenalisib; Romidepsin

Additional relevant MeSH terms:

Lymphoma; Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Romidepsin; Antibiotics, Antineoplastic; Antineoplastic Agents