Romidepsin, CC-486 (5-azacitidine), Dexamethasone, and Lenalidomide (RAdR) for Relapsed/Refractory T-cell Malignancies

Summary

Background:

Mature T-cell malignancies (TCMs) are a rare group of cancers that usually do not have effective treatments or cures. Because of this, participants with TCMs often relapse and have a poor overall prognosis. This trial is testing if combining several drugs against TCMs can be a more effective.

Primary Objective:

To test if the combination of romidepsin, CC-486 (5-azacitidine), dexamethasone, and lenalidomide (RAdR) can be given safely to participants with relapsed or treatment refractory TCM.

Other (Secondary) Objective:

Measure the activity of this combination treatment.

Eligibility:

People age 18 and older who have a failed or relapsed after standard treatments for mature TCMs.

Design:

Participants will be screened for eligibility by performing the following tests or procedures:

Physical exam

Medical history

Medicine review

Blood and urine tests

Symptom review

Bone marrow examination

Total Body imaging scans or x-rays

Tumor biopsy

Participants will have blood tests during treatment to make sure their blood cell counts are okay.

Romidepsin is infused through an intravenous (IV) placed in one of the veins usually in the arm. Lenalidomide, dexamethasone, and CC-486 (5-azacitidine) are pills or capsules taken by mouth.

Participants are asked to keep a diary of when they take their pills to make sure they are taking these medicines properly.

Participants will have tumor imaging scans after every 2nd cycle (or 6 weeks) to check if the treatment is working. If the doctors are concerned the cancer has spread to the brain and/or spine, they will have scans of the area(s) and a sampling of the fluid around the brain/spine which is obtained through a small needle inserted into the lower part of the back for a short time to collect the fluid. This procedure is called a spinal tap or lumbar puncture.

Participants who have tumor in their skin will have repeat exams of their skin and sometimes photographs taken of these areas to see if the treatment is working.

Participants will also be asked to give blood, saliva, and sometimes have optional biopsies of their tumor where these tests are done for research purposes.

After they have completed the protocol treatment (6 cycles), they will be asked to return to clinic 30 days after treatment has ended, then every other month (or 60 days) for the first 6 months, then every 3 months (90 days) for 2 years, and then every 6 months for years 2 to 4 after completing treatment. After 4.5 years, they will be seen once a year.

Conditions

• Cutaneous T-Cell Lymphoma
• Mature T-cell Malignancies
• Peripheral T-Cell Lymphoma
• Relapsed/ Refractory T-cell Malignancies

Interventions

DRUG

Romidepsin

Romidepsin (12mg/ m\^2) will be administered on days 1 and 10 of each cycle through a peripheral or central intravenous catheter for 6 cycles.

DRUG

Lenalidomide

Lenalidomide will be administered by oral intake in a dose-escalation with a starting dose of 5mg daily, a second dose level of 10mg daily, a third dose level at 15mg daily, and a fourth dose level at 20mg daily on days -7 to day 10 of first cycle. After the second cycle, lenalidomide will be given from day 1 to day 10 in each cycle for up to 6 cycles.

DRUG

CC-486 (5-azacitidine)

CC-486 (5-azacitidine) with a dose of 300mg oral intake daily will be given on day 1 to day 10 for 6 cycles.

DRUG

Dexamethasone

Dexamethasone, 40mg, by mouth (PO), will be given on days 1 and 10 of each cycle.

DIAGNOSTIC_TEST

EKG

Screening

PROCEDURE

Bone Marrow Aspiration/Biopsy

Baseline, end of treatment and disease progression, and Day 30 (+7).

DIAGNOSTIC_TEST

MRI

Baseline, every 2 cycles, end of treatment and disease progression, and follow-up.

PROCEDURE

Lumbar Puncture

Baseline, every 2 cycles, end of treatment and disease progression, and follow-up.

DIAGNOSTIC_TEST

TTE

Screening

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Max Gordon, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-12-17

Primary Completion

2024-07-01

Completion

2025-12-17

FDA Drug

Yes

Countries

• United States

Study Locations