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Romidepsin

Histone Deacetylase Inhibitors

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Valine

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.

Parsaclisib

Walter Hanel, MD, PhD

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.

PRIMARY OBJECTIVE:

I. To determine the maximum tolerated dose (MTD) of parsaclisib in combination with romidepsin.

SECONDARY OBJECTIVES:

I. To determine the overall response rate (ORR) of parsaclisib in combination with romidepsin in patients with relapsed/refractory primary cutaneous T-cell non-Hodgkin lymphoma / mature T-cell and NK-cell non-Hodgkin lymphoma (CTCL/PTCL).

II. To determine the duration of response (DOR) to treatment. III. Disease control rate (DCR). IV. To determine the progression-free survival (PFS) and overall survival (OS) of parsaclisib in combination with romidepsin in patients with relapsed/refractory CTCL/PTCL.

OUTLINE: This is a dose-escalation study of parsaclisib in the Induction Phase and fixed-dose in the Maintenance phase, and fixed-dose romidepsin in all Phases.

PRE-PHASE: Patients receive romidepsin intravenously (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 orally (PO) once daily (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.

After completion of study treatment, patients are followed up at 30 days and then every 3 months for up to 2 years.

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

A Phase I Study of Romidepsin in Combination With Parsaclisib in Relapsed and Refractory T-Cell Lymphomas

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

ORR defined as the proportion of patients who achieve a complete or partial response among all evaluable patients. The proportion will be provided with a 95% binomial confidence interval. For mature T-Cell and NK-Cell Non-Hodgkin lymphoma (PTCL) patients, response will be evaluated by the Lugano criteria. For primary cutaneous T-Cell Non-Hodgkin lymphoma (CTCL) patients, responses will be evaluated using the Global Response Score. ORR lasting \>= 4 months will be captured for CTCL patients.

DOR defined by time to progression; time from the first romidepsin dose until disease progression.

PFS will be calculated from the start of the combination treatment to the time of progression or death, whichever occurs first. Will use the method of Kaplan-Meier to describe these survival endpoints; reporting median or estimates at certain time points with 95% confidence intervals.

Will use the method of Kaplan-Meier to describe these survival endpoints; reporting median or estimates at certain time points with 95% confidence intervals.

DCR is defined as the proportion of patients with complete response, partial response, or stable disease.

Walter Hanel

Principal Investigator

Spots Global Cancer Trial Database for recurrent transformed mycosis fungoides