Clinical trial NCT03770000: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: T Cell Lymphoma
Keywords: T cell Lymphoma
RP6530
Tenalisib
Romidepsin
Lead sponsor: Rhizen Pharmaceuticals SA
Sponsor class: INDUSTRY
First posted: 2018-12-10
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of Participants With and Without Dose Limiting Toxicities (DLTs)
timeFrame: 28 days
Secondary outcomes:
measure: Overall Response Rate (ORR) With Tenalisib and Romidepsin Combination
timeFrame: 12 weeks
measure: Duration of Response (DoR) With Tenalisib and Romidepsin Combination
timeFrame: 28 weeks
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: 8 days
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: University of California, Hellen Diller Family Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Miami
country: United States
facility: University of Miami-Sylvester Comprehensive Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Chicago
country: United States
facility: Rush University Cancer Center
state: Illinois
city: Fairway
country: United States
facility: The University of Kansas Cancer Center
state: Kansas
city: Louisville
country: United States
facility: Norton Cancer Institute, St Matthews Campus
state: Kentucky
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Hackensack
country: United States
facility: John Theurer Cancer Center, Hackensack University Medical Center
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Institute
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Nashville
country: United States
facility: Vanderbilt Ingram Cancer Center
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center,
state: Texas
Study officials:
References: