Phase 1
N=20
Romidepsin, CC-486 (5-azacitidine), Dexamethasone, and Lenalidomide (RAdR) for Relapsed/Refractory T-cell Malignancies
Cutaneous T-Cell Lymphoma · Mature T-cell Malignancies · Peripheral T-Cell Lymphoma · Relapsed/ Refractory T-cell Malignancies
Bottom Line
View on ClinicalTrials.gov: NCT04447027 ↗Enrolled (actual)
20
Serious AEs
19.2%
Results posted
Jun 2025
Primary outcome: Primary: Maximum Tolerated Dose (MTD) — 20 mg/day
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Romidepsin (Drug); Lenalidomide (Drug); CC-486 (5-azacitidine) (Drug); Dexamethasone (Drug); EKG (Diagnostic_test); Bone Marrow Aspiration/Biopsy (Procedure); MRI (Diagnostic_test); Lumbar Puncture (Procedure); TTE (Diagnostic_test)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- National Cancer Institute (NCI)
- Primary completion
- Jul 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Tolerated Dose (MTD) |
20 | — |
| PRIMARY Rate and Severity of Serious and/or Non-serious Adverse Events (AE's) by Grade and Type of Toxicity |
0; 0; 1; 1; 0; 0 | — |
| PRIMARY Number of Treatment Emergent Grades 3, 4 and/or 5 Adverse Events Possibly Related to Drug Grouped by Severity |
13; 9; 0; 4; 1; 4 | — |
| PRIMARY Arm 1, Cohort 1, Dose Level -1, 1, and 2 Treatment Emergent Serious Grades 3, 4, and/or 5 Adverse Events Possibly Related to Drug Grouped by Relationship to the Study Drug and/or Combination |
0; 0; 0; 0; 0; 1 | — |
| PRIMARY Arm 1, Cohort 1, Dose Level 3, and Arm 1, Cohort 1, Dose Level 4 Treatment Emergent Serious Grades 3, 4, and/or 5 Adverse Events Possibly Related to Drug Grouped by Relationship to the Study Drug and/or Combination |
1; 1; 1; 1; 0; 0 | — |
| PRIMARY Arm 2, Cohort 2, Dose Level 2 and 4; and Arm 3, Cohort 2, Dose Level 4 Treatment Emergent Serious Grades 3, 4, and/or 5 Adverse Events Possibly Related to Drug Grouped by Relationship to the Study Drug and/or Combination |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Overall Response Rate (Complete Response + Partial Response) |
50; 16.6; 33.3; 66; 100; 50 | — |
| SECONDARY Progression-free Survival (PFS) in Months Reported Along With a 95% Confidence Interval |
5.3; 1.7; NA; 3.7; 9.2; 3.6 | — |
| SECONDARY Complete Response Rate (CRR) |
0; 16.6; 0; 0; 0; 0 | — |
| SECONDARY Duration of Response (DOR) in Months Reported Along With a 95% Confidence Interval |
5.8; NA; NA; 2.1; 6.0; 3.4 | — |
| SECONDARY Overall Survival (OS) |
8.7; 4.6; NA; NA; NA; 4.5 | — |
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.
Eligibility Criteria
- INCLUSION CRITERIA:
- Patients must have relapsed after or progressed during at least one line of prior systemic therapy (which may include allogeneic stem cell transplantation) for mature T or NK/T neoplasm, i.e. have relapsed and/or refractory mature T and natural killer (NK) neoplasm per 2016 World Health Organization (WHO) classification excluding chronic lymphoproliferative disorder of NK cells, aggressive NK-cell leukemia, and Cutaneous T-Cell Lymphoma.
- T or NK/T neoplasm from initial diagnosis or recurrence must be histologically or cytologically proven and diagnosis be confirmed by the Laboratory of Pathology, National Cancer Institute (NCI),
- Patients with anaplastic large cell lymphoma (ALCL) or cluster of differentiation (CD30) positive mycosis fungoides (MF) or Sézary syndrome (SS) must have relapsed after or become intolerant to prior anti-CD30 targeting therapy treatment with brentuximab vedotin
- For patients without circulating leukemia/lymphoma cells detectable by flow cytometry, a formalin fixed tissue block or 15 slides of tumor sample (archival or fresh) must be available at enrollment for performance of correlative studies. NOTE: Patients without circulating malignant cells must be willing to have a tumor biopsy if prior tissue or adequate archival tissue is not available (i.e., post-enrollment and prior to treatment).
- Disease must be measurable with at least one measurable lesion by response evaluation criteria in lymphoma (RECIL) 2017 or Modified Severity-Weighted Assessment Tool (mSWAT) criteria, or have an abnormal clonal T-cell population detectable by peripheral blood flow cytometry
- Age >18 years
- Eastern Cooperative Oncology Group (ECOG) performance status = 1,000/mcL
- Platelets >= 75,000/mcL
- Total bilirubin = 60 mL/min/1.73 m^2 as calculated by direct measurement of 24-hour urine for creatinine clearance
- Negative serum or urine pregnancy test at screening for women of childbearing potential (WOCBP) NOTE: WOCBP is defined as any female who has experienced menarche and who has not undergone successful surgical sterilization or who is not postmenopausal. WOCBP must have a negative pregnancy test (hemoglobin (HCG) blood or urine) during screening.
- All study participants must be registered into the mandatory Revlimid REMS(R) program and be willing and able to comply with the requirements of the Risk Evaluation and Mitigation Strategy (REMS(R) program.
- 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, for the duration of study participation, and for at least 6 months after completion of treatment for women, and for at least 3 months after completion of treatment for men. Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS(R) program.
- Ability of subject to understand and the willingness to sign a written informed consent document.
EXCLUSION CRITERIA
- Patients who are receiving any other investigational agents.
- Anti-cancer treatment within 2 weeks prior to enrollment. (4 weeks for monoclonal antibodies and 6 weeks for nitrosoureas or mitomycin C).
- Patients who have received two of the following drugs at any point: lenalidomide, romidepsin, and 5-azacitidine. Patients who have received only one of the three drugs remain eligible.
- Patients with a diagnosis of cutaneous T-cell lymphoma (CTCL) are excluded from participation in the expansion cohort.
- Other malignancy that requires ongoing systemic hormonal therapy, chemotherapy, or immunotherapy.
- History of allergic reactions or known or suspected hypersensitivity attributed to compounds of similar chemical or biologic composition to lenalidomide, romidepsin and 5-azacitidine
- Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring systemic therapy, or psychiatric illness/social situations that
Data sourced from ClinicalTrials.gov (NCT04447027). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.