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

T Cell Lymphoma Clinical Trial

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 Details — Status: Completed

Administrative data

• NCT number: NCT03770000
• Other study ID #: RP6530+Romidepsin-1805
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 12, 2019
• Est. completion date: May 14, 2021

Study information

• Verified date: October 2022
• Source: Rhizen Pharmaceuticals SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: May 14, 2021
• Est. primary completion date: May 14, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Peripheral
• T Cell Lymphoma

Intervention

Drug:
• Tenalisib
Tenalisib, BID orally daily
• Romidepsin
Romidepsin IV

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	Roswell Park Comprehensive Cancer Center	Buffalo	New York
United States	Rush University Cancer Center	Chicago	Illinois
United States	Cleveland Clinic Taussig Cancer Institute	Cleveland	Ohio
United States	The University of Kansas Cancer Center	Fairway	Kansas
United States	John Theurer Cancer Center, Hackensack University Medical Center	Hackensack	New Jersey
United States	The University of Texas MD Anderson Cancer Center,	Houston	Texas
United States	USC/Norris Comprehensive Cancer Center	Los Angeles	California
United States	Norton Cancer Institute, St Matthews Campus	Louisville	Kentucky
United States	University of Miami-Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Vanderbilt Ingram Cancer Center	Nashville	Tennessee
United States	Oregon Health & Science University	Portland	Oregon
United States	University of California, Hellen Diller Family Comprehensive Cancer Center	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Rhizen Pharmaceuticals SA

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Duration of Response (DoR) With Tenalisib and Romidepsin Combination	The time period from the response achieved in patient until the disease progression	28 weeks
Secondary	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