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

Phase 1

Completed

• Conditions: T Cell Lymphoma
• Interventions: Drug: Tenalisib; Drug: Romidepsin

• Registration Number: NCT03770000
• Lead Sponsor: Rhizen Pharmaceuticals SA

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-12-06
• Study First Submitted QC: 2018-12-06
• Study First Posted: 2018-12-10
• Study Start: 2019-03-12
• Primary Completion: 2021-05-14
• Study Completion: 2021-05-14
• Results First Submitted: 2022-05-04
• Status Verified: 2022-10
• Results First Submitted QC: 2022-10-27
• Last Update Submitted: 2022-10-27
• Results First Posted: 2022-10-28
• Last Update Posted: 2022-10-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 33

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Tenalisib+Romidepsin	Tenalisib	Participants receive Tenalisib in escalating doses daily Orally BID and Romidepsin in escalating doses intravenously on day 1, 8 and 15
Tenalisib+Romidepsin	Romidepsin	Participants receive Tenalisib in escalating doses daily Orally BID and Romidepsin in escalating doses intravenously on day 1, 8 and 15

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Overall Response Rate (ORR) With Tenalisib and Romidepsin Combination	12 weeks	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.
Maximum Observed Plasma Concentration (Cmax)	8 days	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.
Duration of Response (DoR) With Tenalisib and Romidepsin Combination	28 weeks	The time period from the response achieved in patient until the disease progression

Trial Locations

Locations (15)

John Theurer Cancer Center, Hackensack University Medical Center; 🇺🇸 Hackensack, New Jersey, United States

University of Colorado Cancer Center; 🇺🇸 Aurora, Colorado, United States

Rush University Cancer Center; 🇺🇸 Chicago, Illinois, United States

Cleveland Clinic Taussig Cancer Institute; 🇺🇸 Cleveland, Ohio, United States

University of California, Hellen Diller Family Comprehensive Cancer Center; 🇺🇸 San Francisco, California, United States

Vanderbilt Ingram Cancer Center; 🇺🇸 Nashville, Tennessee, United States

The University of Texas MD Anderson Cancer Center,; 🇺🇸 Houston, Texas, United States

USC/Norris Comprehensive Cancer Center; 🇺🇸 Los Angeles, California, United States

University of Miami-Sylvester Comprehensive Cancer Center; 🇺🇸 Miami, Florida, United States

Norton Cancer Institute, St Matthews Campus; 🇺🇸 Louisville, Kentucky, United States

Oregon Health & Science University; 🇺🇸 Portland, Oregon, United States

Winship Cancer Institute of Emory University; 🇺🇸 Atlanta, Georgia, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Roswell Park Comprehensive Cancer Center; 🇺🇸 Buffalo, New York, United States

The University of Kansas Cancer Center; 🇺🇸 Fairway, Kansas, United States