Romidepsin and Parsaclisib for the Treatment of Relapsed or Refractory T-Cell Lymphomas

NCT04774068 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: OSU-19264NCI-2021-00728
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial finds the appropriate parsaclisib dose level in combination with romidepsin for the treatment of T-cell lymphomas that have come back (relapsed) or that have not responded to standard treatment (refractory). The other goals of this trial are to find the proportion of patients whose cancer is put into complete remission or significantly reduced by romidepsin and parsaclisib, and to measure the effectiveness of romidepsin and parsaclisib in terms of patient survival. Romidepsin blocks certain enzymes (histone deacetylases) and acts by stopping cancer cells from dividing. Parsaclisib is a PI3K inhibitor. The PI3K pathway promotes cancer cell proliferation, growth, and survival. Parsaclisib, thus, may stop the growth of cancer cells by blocking PI3K enzymes needed for cell growth. Giving romidepsin and parsaclisib in combination may work better in treating relapsed or refractory T-cell lymphomas compared to either drug alone.

Conditions

Recurrent Anaplastic Large Cell Lymphoma; Recurrent Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Transformed Mycosis Fungoides; Refractory Anaplastic Large Cell Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Transformed Mycosis Fungoides; T-Cell Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD) of parsaclisib

  Will use a time-to-event Bayesian optimal interval design to identify the MTD of this combination regimen.

  Cycles 3-5 (each cycle is 28 days)

Secondary Outcomes (5)

• Overall response rate (ORR)

  Up to 24 weeks

• Duration of response (DOR)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

• Progression-free survival (PFS)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

• Overall survival (OS)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

• Disease control rate (DCR)

  Up to 2 years

Study Arms (1)

Treatment (romidepsin, parsaclisib)

EXPERIMENTAL

PRE-PHASE: Patients receive romidepsin IV over 4 hours on days 1, 8, and 15. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. INDUCTION PHASE: Patients receive romidepsin IV over 4 hours on days 1,8, and 15 and parsaclisib PO QD on days 1-28. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive romidepsin IV over 4 hours on days 1, 8, and 15 and parsaclisib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Parsaclisib; Drug: Romidepsin

Interventions

Parsaclisib DRUG

Given PO

Also known as: (4R)-4-(3-((1S)-1-(4-Amino-3-methyl-1H-pyrazolo(3,4-d)pyrimidin-1-yl)ethyl)-5-chloro-2-ethoxy-6-fluorophenyl)pyrrolidin-2-one, INCB 50465, INCB-50465, INCB050465, INCB50465, WHO 10589

Treatment (romidepsin, parsaclisib)

Romidepsin DRUG

Given IV

Also known as: Antibiotic FR 901228, Depsipeptide, FK228, FR901228, Istodax, N-[(3S,4E)-3-Hydroxy-7-mercapto-1-oxo-4-heptenyl]-D-valyl-D-cysteinyl-(2Z)-2-amino-2-butenoyl-L-valine, (4->1) Lactone, Cyclic

Treatment (romidepsin, parsaclisib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>= 18 years
• Able to understand and voluntarily sign a consent form
• Biopsy proven diagnosis of PTCL or CTCL
• Relapsed/refractory PTCL, progressing after at least one line of systemic therapy (for anaplastic large cell lymphoma \[ALCL\], must have had prior treatment with brentuximab vedotin). OR
• Relapsed/Refractory CTCL, that progressed on at least 2 lines of skin-directed (topical) therapy and/or one line of systemic therapy. Pre-treatment with mogamulizumab and/or brentuximab vedotin (in the presence of CD30 positive disease) is NOT required as a criterion for eligibility. Skin-directed therapies include, but are not limited to topical steroids, topical chemotherapy, imiquimod, narrow band ultraviolet B (UVB), psoralen plus ultraviolet A photochemotherapy (PUVA), total skin electron beam radiation, and extracorporeal photopheresis
• Mycosis fungoides with large cell transformation is eligible
• Performance status (Eastern Cooperative Oncology Group \[ECOG\]) 0-2
• Life expectancy \>= 90 days
• Patient must have at least stage IB CTCL (\> 10% eBSA) or PTCL with disease defined by a nodal area of at least 1.5 cm in long dimension, extranodal disease of at least 1 cm in long dimension, or fludeoxyglucose F-18 - positron emission tomography (FDG-PET) avid disease (Deauville score = 5)
• Absolute neutrophil count (ANC) \>= 1,000/mm\^3
• Platelet count \>= 100,000/mm\^3
• Calculated creatinine clearance \>= 50mL/min (Cockcroft-Gault method)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x institutional upper limit of normal (ULN) or =\< 5 x ULN if liver involved by lymphoma
• Bilirubin =\< 2.0 x ULN. If the subject has Gilbert's disease, low-grade hemolysis, or liver involvement with lymphoma, a bilirubin level of =\< 4 x ULN will be allowed
• Negative serum pregnancy test at the time of enrollment for females of childbearing potential

You may not qualify if:

• Patients with uncontrolled central nervous system (CNS) disease
• Use of immunosuppressive therapy within 28 days of randomization. Immunosuppressive therapy includes, but is not limited to, cyclosporine A, tacrolimus, or high-dose corticosteroids. Participants receiving corticosteroids must be at a dose of =\< 10 mg/day prednisone (or equivalent) within 7 days of randomization. However, topical steroids (maximum strength Class III according to World Health Organization Classification of Topical steroids) are allowed to control pruritis
• An active infection requiring a systemic antimicrobial. The patient should be off antibiotic treatment for an active infection for 7 days prior to enrollment in the trial. However, antibiotic prophylaxis is acceptable as long as the dose of the medication has been stable for at least 7 days prior to the baseline exam
• Exposure to a live vaccine within 30 days of treatment start
• Positive at the time of screening for human immunodeficiency virus (HIV), hepatitis B surface antigen or viral load, hepatitis C viral load. Hepatitis B (HBV) or hepatitis C (HCV) infection: Participants positive for HBV surface antigen or HBV core antibody will be eligible if they are negative for HBV-deoxyribonucleic acid (DNA); these participants should be considered for prophylactic antiviral therapy. Participants positive for anti-HCV antibody will be eligible if they are negative for HCV ribonucleic acid (RNA)
• Prior malignancy within the past 2 years (allowing squamous cell and basal cell carcinomas with free margins at excision)
• Prior treatment with a PI3K inhibitor
• Presence of an abnormal electrocardiogram (ECG) that is clinically meaningful. Screening corrected QT interval (QTc) interval \> 450 milliseconds is excluded (corrected by Fridericia). In the event that a single QTc is \> 450 milliseconds, the participant may enroll if the average QTc for 3 ECGs is \< 450 milliseconds. If left bundle branch is present, upper limit of QTc will be 550 milliseconds
• Use of strong CYP3A4 inhibitors and inducers. If a CYP3A4 inhibitor was recently used, there should be 14 days or 5 half-lives time (whichever is longer) before the first dose of parsaclisib is administered. Use of moderate CYP3A4 inhibitors are strongly discouraged but not strictly prohibited. If a strong CYP3A4 inhibitor is started after study enrollment, the study principal investigator (PI) should be contacted to discuss alternatives
• Unable to swallow tablets, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction likely to interfere with the delivery, absorption, or metabolism of parsaclisib
• Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
• Progression while on romidepsin or within 3 months of discontinuation of romidepsin. Prior treatment with romidepsin is allowed if it was well-tolerated
• Unwillingness to comply with study procedures, including follow-up, as specified by this protocol, or unwillingness to cooperate fully with the investigator
• Pregnant or lactating, or intending to become pregnant during the study

Sponsors & Collaborators

• Walter Hanel: lead

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Links

• The Jamesline

MeSH Terms

Conditions

Lymphoma, Large-Cell, Anaplastic; Lymphoma, T-Cell; Lymphoma, T-Cell, Cutaneous

Interventions

parsaclisib; romidepsin; Depsipeptides; Lactones

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Organic Chemicals

Study Officials

• Walter Hanel, MD, PhD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 19, 2021
• First Posted: February 26, 2021
• Study Start: September 1, 2021
• Primary Completion: October 27, 2024
• Study Completion: October 27, 2024
• Last Updated: January 17, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)