RAdR Regimen for T-Cell Lymphoma

Overseen By Mark J Roschewski, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Rifampin, Strong CYP3A4 inhibitors

Disqualifiers: Other malignancy, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 31

Duration: 6 cycles (28-day cycle each)

20 Participants Needed

Trial Summary

What is the purpose of this trial?

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 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.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot participate if you are on other investigational drugs or certain medications that affect heart rhythm. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

What data supports the effectiveness of the drug romidepsin for T-cell lymphoma?

Romidepsin has shown effectiveness in treating relapsed or refractory T-cell lymphoma, with studies reporting overall response rates of 25% to 38% and some patients achieving complete responses. It is approved by the FDA for this use, and patients with good responses to the drug have experienced longer survival times. ^{1 2 3 4 5}

Is the RAdR Regimen for T-Cell Lymphoma safe for humans?

Romidepsin, a part of the RAdR Regimen, has been studied for safety in T-cell lymphoma patients. Common side effects include blood-related issues like low white blood cell counts and infections, but overall, it has an acceptable safety profile. ^{1 2 3 4 6}

What makes the RAdR regimen for T-cell lymphoma unique?

The RAdR regimen combines CC-486 (5-azacitidine), Lenalidomide, and Romidepsin, which is unique because it includes Romidepsin, a histone deacetylase inhibitor that modifies the epigenome and has shown strong antitumor activity in T-cell lymphomas, offering a novel approach compared to traditional chemotherapies. ^{1 2 4 7 8}

Research Team

Mark J Roschewski, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

Adults over 18 with relapsed or treatment-resistant mature T-cell malignancies, who have tried at least one line of systemic therapy. They must be able to sign consent, meet specific blood and organ function criteria, agree to contraception use if applicable, and not be pregnant or breastfeeding. Prior tissue samples for study are required unless a new biopsy is agreed upon.

Inclusion Criteria

- Total bilirubin <= 1.5 X institutional upper limit of normal (ULN)

- Ability of subject to understand and the willingness to sign a written informed consent document.

I can provide a tumor sample or am willing to have a biopsy if needed.

Exclusion Criteria

I haven't had any cancer treatment in the last 2 weeks.

I have been treated with two out of lenalidomide, romidepsin, and 5-azacitidine.

I do not have serious heart conditions or recent major heart events.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive a combination of romidepsin, CC-486 (5-azacitidine), dexamethasone, and lenalidomide for up to 6 cycles

6 cycles (28-day cycle each)

Visits every 28 days for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4.5 years

Every 2 months for 6 months, every 3 months for 2 years, every 6 months for 2 years, then annually

Treatment Details

Interventions

• CC-486 (5-azacitidine)
• Dexamethasone
• Lenalidomide
• Romidepsin

Trial Overview The trial tests the safety and effectiveness of combining romidepsin (IV), CC-486 (oral), dexamethasone (oral), and lenalidomide (oral) in treating T-cell malignancies that haven't responded well to other treatments. Participants will undergo regular physical exams, imaging scans every six weeks, blood tests during treatment, and follow-ups post-treatment.

Participant Groups

Group I: 2 - Experimental Treatment: Dose Expansion Experimental Treatment 4 Interventions

Lenalidomide by oral intake at MTD on days -7 to 10 of each 21-day cycle (max 6 cycles) with CC-486 (5-azacitidine) at 300mg/day by oral intake on days 1-10, romidepsin at 12mg/m2 by IV infusion on Day 1 and 10 and dexamethasone at 40mg by oral intake on days 1 and 10 of each cycle

Group II: 1- Experimental Treatment: Dose Escalation Experimental Treatment 4 Interventions

Lenalidomide by oral intake at escalating doses of 5, 10, 15, or 20 mg/day on days -7 to 10 of each 21-day cycle (max 6 cycles) with CC-486 (5-azacitidine) at 300mg/day by oral intake on days 1-10, romidepsin at 12mg/m2 by IV infusion on Day 1 and 10 and dexamethasone at 40mg by oral intake on days 1 and 10 of each cycle, to determine MTD

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

Romidepsin, a histone deacetylase inhibitor, shows significant clinical activity in patients with relapsed peripheral T-cell lymphoma (PTCL), achieving an overall response rate of 38% in a phase 2 trial involving 45 patients.

The treatment resulted in durable responses, with a median duration of response lasting 8.9 months, indicating its potential effectiveness even in patients with a history of multiple prior therapies, including stem-cell transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 trial of romidepsin in patients with peripheral T-cell lymphoma. Piekarz, RL., Frye, R., Prince, HM., et al.[2021]

Romidepsin, an antitumor drug that inhibits histone deacetylase (HDAC), showed a treatment response rate of 42.5% in a phase II study involving 40 Japanese patients with relapsed or refractory peripheral T-cell lymphoma (PTCL).

The safety profile of romidepsin was deemed acceptable, with common severe side effects including lymphopenia (74%), neutropenia (54%), and leukocytopenia (46%), leading to its approval for PTCL treatment in Japan in July 2017.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Romidepsin (Istodax&#174; for intravenous injection 10&#8197;mg): pharmacokinetics, pharmacodynamics and clinical study outcome]. Ro, T., Nakayama, N., Achiwa, H., et al.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Romidepsin treatment for relapsed or refractory peripheral and cutaneous T-cell lymphoma: Real-life data from a national multicenter observational study. [2020]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Romidepsin: a guide to its clinical use in cutaneous T-cell lymphoma. [2016]

3. United States pubmed.ncbi.nlm.nih.gov

Phase 2 trial of romidepsin in patients with peripheral T-cell lymphoma. [2021]

4. Japan pubmed.ncbi.nlm.nih.gov

[Romidepsin (Istodax&#174; for intravenous injection 10&#8197;mg): pharmacokinetics, pharmacodynamics and clinical study outcome]. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Romidepsin for the treatment of relapsed/refractory peripheral T cell lymphoma: prolonged stable disease provides clinical benefits for patients in the pivotal trial. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Nursing Roles in Cardiac Safety: Romidepsin in Patients With T-Cell Lymphoma. [2017]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Panoptic clinical review of the current and future treatment of relapsed/refractory T-cell lymphomas: Cutaneous T-cell lymphomas. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Romidepsin for cutaneous T-cell lymphoma. [2019]