Poly ICLC, Radiation, and Romidepsin for Advanced Cutaneous T Cell Lymphoma

NCT02061449 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: 13-00686
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates the safety and tolerability of the addition of immunostimulatory therapy consisting of focal radiation with or without the Toll-like receptor (TLR) agonist Poly ICLC in patients with cutaneous T-cell lymphoma (CTCL) receiving concurrent therapy with the histone deacetylase inhibitor (HDACI) Romidepsin.

Conditions

Cutaneous T-cell Lymphoma

Keywords

Toll-like receptor agonist; immunostimulation

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD)

  Adverse events and dose-limiting toxicities will be graded using National Cancer Institute's Common Toxicity Criteria for Adverse Effects (CTCAE) 4.0.

  21 days

Secondary Outcomes (3)

• Overall response rate

  Up to 12 months

• Median progression-free survival

  up to 12 months

• Median overall survival

  up to 12 months

Study Arms (2)

Initiating therapy with Romidepsin (Arm A)

EXPERIMENTAL

Patients who are starting therapy with Romidepsin (intravenously on days 1, 8, and 15 of every 21-day cycle or alternate schedule per treating physician) also receive focal lesional radiation on days 1,3, and 5 without (level 1) or with (level 2) Poly ICLC (subcutaneously on days 1, 3, and 5) on the first cycle.

Drug: Romidepsin; Drug: Poly ICLC; Radiation: Focal lesional radiation

treatment with Romidepsin with SD or PR (Arm B)

EXPERIMENTAL

Patients with stable disease on the treatment with Romidepsin (intravenously on days 1, 8, and 15 of every 21-day cycle or alternate schedule per treating physician) also receive focal lesional radiation on days 1,3, and 5 without (level 1) or with (level 2) Poly ICLC (subcutaneously on days 1, 3, and 5) on the first cycle.

Drug: Romidepsin; Drug: Poly ICLC; Radiation: Focal lesional radiation

Interventions

Romidepsin DRUG

Also known as: Istodax, FK228, FR901228

Initiating therapy with Romidepsin (Arm A); treatment with Romidepsin with SD or PR (Arm B)

Poly ICLC DRUG

Initiating therapy with Romidepsin (Arm A); treatment with Romidepsin with SD or PR (Arm B)

Focal lesional radiation RADIATION

Initiating therapy with Romidepsin (Arm A); treatment with Romidepsin with SD or PR (Arm B)

Eligibility Criteria

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

You may qualify if:

• Must have prior biopsy at any time point diagnostic for confirmed MF stage IIA-IVA, and must have failed at least one standard therapy (topical or systemic).
• Must have a skin lesion of at minimum 2 cm, in a location amenable to radiation and a minimum of 2 additional measurable skin lesions distant from the radiation site.
• Must be either initiating therapy with romidepsin (Arm A) or currently receiving romidepsin with documented stable disease (SD) or partial response (PR) (Arm B).
• Patient may have had any prior topical or systemic therapy except for total electron beam irradiation. Patients must be a minimum of 2 weeks from topical therapy and 4 weeks from systemic therapies, phototherapy, or local radiation therapy before enrollment except for HDACI if they are in Arm B. Patients are allowed to take weak potency topical corticosteroids if patient has been on a stable dose for more than a month.
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>70%)
• Life expectancy of greater than 6 months
• Patients must have normal organ and marrow function as defined below:
• leukocytes \>=2,500/mcL
• absolute neutrophil count \>=1,000/mcL
• platelets \>=50,000/mcL
• total bilirubin: within normal institutional limits
• AST(SGOT, aspartate aminotransferase)/ALT(SGPT, alanine aminotransferase) =\<2.5 X institutional upper limit of normal
• creatinine: within normal institutional limits OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal.
• Age \>=18 years
• The effects of focal radiation and HDACI on the developing human fetus are unknown. For this reason and because agents as well as other therapeutic agents used in this trial are known to be tetragenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 4 weeks, or topical therapy within 2 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. Patients are allowed to take weak potency topical corticosteroids if patient has been on a stable dose for more than a month.
• Patients who are receiving any other investigational agents.
• Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to HDACI, TLR-agonist, or patients with known history of pre-existing auto-immune disease.
• Concurrent therapy with systemic corticosteroids or other immunosuppressive medications.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study HDACI is a class agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with HDACI, breastfeeding should be discontinued if the mother is treated with HDACI and radiation. Woman of childbearing age and men sexually active with woman of childbearing age must agree to an acceptable method of birth control (double barrier) while on study.
• Patients with known HIV infection are ineligible because this immunomodulatory therapy requires a normal and functional T cell repertoire. If this study is found to be safe, effective, and immunogenic, HIV positive patients may be included in future studies.

Sponsors & Collaborators

• NYU Langone Health: lead
• Ludwig Institute for Cancer Research: collaborator

Study Sites (1)

NYU Cancer Institute

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Lymphoma, T-Cell, Cutaneous

Interventions

romidepsin; poly ICLC

Condition Hierarchy (Ancestors)

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

Study Officials

• Catherine Diefenbach, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2014
• First Posted: February 12, 2014
• Study Start: March 1, 2014
• Primary Completion: November 5, 2018
• Study Completion: November 5, 2018
• Last Updated: December 24, 2018

Record last verified: 2018-12

Locations

US (1)