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

NCT ID: NCT03770000

Last Updated: 2022-10-28

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

33 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-03-12

Study Completion Date

2021-05-14

Brief Summary

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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

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Conditions

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T Cell Lymphoma

Study Design

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Allocation Method

NA

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Tenalisib+Romidepsin

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

Group Type EXPERIMENTAL

Tenalisib

Intervention Type DRUG

Tenalisib, BID orally daily

Romidepsin

Intervention Type DRUG

Romidepsin IV

Interventions

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Tenalisib

Tenalisib, BID orally daily

Intervention Type DRUG

Romidepsin

Romidepsin IV

Intervention Type DRUG

Other Intervention Names

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RP6530

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Rhizen Pharmaceuticals SA

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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USC/Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

University of California, Hellen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Site Status

University of Colorado Cancer Center

Aurora, Colorado, United States

Site Status

University of Miami-Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Site Status

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Site Status

Rush University Cancer Center

Chicago, Illinois, United States

Site Status

The University of Kansas Cancer Center

Fairway, Kansas, United States

Site Status

Norton Cancer Institute, St Matthews Campus

Louisville, Kentucky, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

John Theurer Cancer Center, Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Roswell Park Comprehensive Cancer Center

Buffalo, New York, United States

Site Status

Cleveland Clinic Taussig Cancer Institute

Cleveland, Ohio, United States

Site Status

Oregon Health & Science University

Portland, Oregon, United States

Site Status

Vanderbilt Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

The University of Texas MD Anderson Cancer Center,

Houston, Texas, United States

Site Status

Countries

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United States

References

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Iyer SP, Huen A, Ai WZ, Jagadeesh D, Lechowicz MJ, Okada C, Feldman TA, Ghione P, Alderuccio JP, Champion R, Kim SH, Mohrbacher A, Routhu KV, Barde P, Nair AM, Haverkos BM. Safety and efficacy of tenalisib in combination with romidepsin in patients with relapsed/refractory T-cell lymphoma: results from a phase I/II open-label multicenter study. Haematologica. 2024 Jan 1;109(1):209-219. doi: 10.3324/haematol.2022.281875.

Reference Type DERIVED
PMID: 37439343 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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RP6530+Romidepsin-1805

Identifier Type: -

Identifier Source: org_study_id

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