26 Participants Needed

RAdR Regimen for T-Cell Lymphoma

NM
KC
MJ
Overseen ByMark J Roschewski, M.D.
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a combination of four drugs—romidepsin, CC-486 (5-azacitidine), dexamethasone, and lenalidomide—can safely treat people with mature T-cell lymphoma, a rare cancer. These cancers often return after standard treatments, and the study aims to provide a new option for those whose previous treatments have failed. Participants should have already tried and not succeeded with standard therapies for T-cell malignancies. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the treatments in this trial—romidepsin, CC-486 (5-azacitidine), lenalidomide, and dexamethasone—have been tested for safety in earlier studies.

Romidepsin has been used for other T-cell lymphomas. Studies indicate it can cause side effects related to blood and common reactions like nausea or tiredness, but it is generally considered safe for these conditions.

CC-486 (5-azacitidine) has been tested in patients with similar blood cancers. Some patients needed to adjust their doses due to side effects like low blood counts, though serious side effects are rare but possible.

Lenalidomide is already approved for other T-cell lymphomas. It is generally safe, though some patients might experience side effects like low blood counts or tiredness.

Dexamethasone, a steroid that helps reduce inflammation, is widely used and generally safe, though it might cause side effects like weight gain or mood changes.

Overall, while each drug can cause side effects, they are usually manageable. Researchers will closely monitor participants in this trial to ensure their safety.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about the RAdR regimen for T-cell lymphoma because it combines three promising drugs: lenalidomide, CC-486 (5-azacitidine), and romidepsin. Unlike the standard of care, which often involves chemotherapy and immunotherapy, this regimen targets cancer cells through epigenetic modulation and immune system enhancement. CC-486 is an oral form of azacitidine, making it more convenient than traditional injections, while romidepsin, a histone deacetylase inhibitor, offers a novel mechanism by modifying gene expression to inhibit cancer growth. This innovative combination has the potential to be more effective and easier to administer than existing treatments.

What evidence suggests that this trial's treatments could be effective for T-cell lymphoma?

Research has shown that the drug CC-486 (also known as 5-azacitidine) holds potential for treating T-cell lymphomas, with some studies indicating a 75% overall response rate. Lenalidomide has also undergone testing, yielding varying results; about 30% of patients in certain studies experienced partial improvement. Romidepsin, when combined with other treatments, demonstrated a 58% overall response rate. In this trial, participants will receive a combination of these drugs, along with Dexamethasone, in different dosing regimens to evaluate their combined effect. The goal is to achieve better results than using each drug separately.25678

Who Is on the Research Team?

MJ

Mark J Roschewski, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

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.
See 14 more

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.
See 16 more

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Group I: 2 - Experimental Treatment: Dose ExpansionExperimental Treatment9 Interventions
Group II: 1- Experimental Treatment: Dose EscalationExperimental Treatment9 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials
14,080
Recruited
41,180,000+

Published Research Related to This Trial

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.
[Romidepsin (Istodax&#174; for intravenous injection 10&#8197;mg): pharmacokinetics, pharmacodynamics and clinical study outcome].Ro, T., Nakayama, N., Achiwa, H., et al.[2018]
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.
Phase 2 trial of romidepsin in patients with peripheral T-cell lymphoma.Piekarz, RL., Frye, R., Prince, HM., et al.[2021]

Citations

Multicenter phase 2 study of oral azacitidine (CC-486) plus ...With the exception of anaplastic large cell lymphoma (ALCL), CHOP typically delivers a overall response rate (ORR) of 60% to 80%, complete ...
Multicenter phase 2 study of oral azacitidine (CC-486) plus ...With the exception of anaplastic large cell lymphoma (ALCL), CHOP typically delivers a overall response rate (ORR) of 60% to 80%, complete response (CR) of 30% ...
Efficacy and Safety of Oral Azacitidine (CC-486) Compared ...This study is a multicentric, open-label, randomized phase 3 trial. The study will be conducted in select countries in Europe and South Korea sponsored by ...
Paper: Subsequent Treatment and Clinical Outcome ...We previously reported the efficacy including induction response rates (ORR 75% and CR 75%) and early survival outcome (2-yr OS 69% and 2-yr PFS 66%)
Alliance A059102: A randomized phase II U.S. intergroup ...Azacitidine is a hypomethylating agent that has shown a 75% overall response rate (ORR) in PTCL with TFH phenotype. CC-486, oral azacitidine, ...
Doxorubicin, CC-(486) (5-azacitidine), Romidepsin, and ...To determine the safety and toxicity profile, maximum tolerated dose (MTD), and the recommended phase II dose (RP2D) of the four-drug combination of CC-486 (5- ...
A Phase I, Open Label, Multicenter Trial of Oral Azacitidine ...CC-486 dose reduction occurred in 9 (27%) pts due to adverse events (AEs). Treatment with CC-486 (150 mg) was discontinued in 1 patient due to febrile ...
Real-world data of azacitidine for relapsed/refractory nodal ...However, a grade 3 or 4 hematological toxicity occurred in nine patients. Azacitidine may be a suitable treatment option for some patients with r/r nodal T- ...
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