Recruiting
Phase 1

Lenalidomide with EPOCH

Sponsor:

National Cancer Institute (NCI)

Code:

NCT04301076

Conditions

Acute Adult T-Cell Leukemia/Lymphoma

Adult T-Cell Leukemia/Lymphoma

Chronic Adult T-Cell Leukemia/Lymphoma

HTLV-1 Infection

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Bone Marrow Biopsy

Computed Tomography

Cyclophosphamide

Doxorubicin Hydrochloride

Study Details

Brief summary:

This phase I trial studies the side effects and best dose of lenalidomide when given together with usual combination chemotherapy (etoposide, prednisone, vincristine sulfate \[Oncovin\], cyclophosphamide, and doxorubicin hydrochloride \[hydroxydaunorubicin hydrochloride\], or "EPOCH") in treating adult T-cell leukemia-lymphoma. Lenalidomide may help shrink or slow the growth of adult T-cell leukemia-lymphoma. Drugs used in chemotherapy, such as etoposide, vincristine, cyclophosphamide, and doxorubicin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Anti-inflammatory drugs such as prednisone lower the body's immune response and are used with other drugs in the treatment of some types of cancer. Giving lenalidomide and the usual combination chemotherapy may work better in treating adult T-cell leukemia-lymphoma compared to the usual combination chemotherapy alone.

Conditions

Acute Adult T-Cell Leukemia/Lymphoma

Adult T-Cell Leukemia/Lymphoma

Chronic Adult T-Cell Leukemia/Lymphoma

HTLV-1 Infection

Study ID

NCT04301076

Start date

Aug 31, 2021

Status verified date

Jul, 2026

Completion date

Jun 30, 2027

Anticipated

Primary completion date

Jun 30, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed CD2+, CD3+, or CD4+ acute, lymphoma or poor-risk chronic subtypes of ATLL including previously untreated or previously treated individuals who have received no more than 1 previous cycle of EPOCH, cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP), or cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide (CHOPE)
  • Patients previously treated with azidothymidine (AZT), interferon (IFN), bexarotene, or mogamulizumab are eligible. Patients with stable disease at high risk of relapse from prior non-combination chemotherapy containing treatment are eligible to participate
  • Documentation of HTLV infection by enzyme-linked immunosorbent assay (ELISA) in individuals with confirmation of HTLV-1 infection (by immunoblot or polymerase chain reaction \[PCR\]) or a consistent clinical picture (including two of three of: 1) CD4+ leukemia or lymphoma, 2) hypercalcemia, and/or 3) Japanese, Caribbean, or South American birthplace) is required for enrollment. Confirmation of HTLV-1 infection is required to continue the subject on protocol after the first cycle of therapy. Patients will be enrolled based on reports from local or referral labs (e.g., Mayo Clinic or LabCorp). Confirmation will be performed by Ratner Lab at Washington University, retrospectively, but this is not a Clinical Laboratory Improvement Amendments (CLIA) assay and is not reimbursed by insurance
  • Age ≥ 18 years

  • Because no dosing or adverse event (AE) data are currently available on the use of lenalidomide in combination with EPOCH in patients < 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Absolute neutrophil count >= 1,000/mm\^3 unless decreased due to bone marrow (BM) involvement with lymphoma
  • Platelets >= 100,000/mm\^3 unless decreased due to BM involvement with lymphoma
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN), if potentially due to lymphoma, in the dose-expansion cohort, the first cycle may be given without lenalidomide and if transaminitis and bilirubinemia improves to meet parameters, participant may be enrolled
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =< 2 x institutional ULN, if potentially due to lymphoma, in the dose-expansion cohort, the first cycle may be given without lenalidomide and if transaminitis and bilirubinemia improve to meet parameters, participant may be enrolled
  • Creatinine =< institutional ULN OR glomerular filtration rate (GFR) >= 60 mL/min/1.73 m\^2 for participants with creatinine levels above institutional normal
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
  • Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
  • Patients must have a life expectancy > 12 weeks
  • Patients must have no serious active infection requiring therapy at the time of study entry
  • Patients must not require the concurrent use of chemotherapy, interferon, zidovudine, arsenic, radiation therapy, or other specific anti-tumor therapy, during the course of this study
  • The effects of lenalidomide on the developing human fetus are unknown. Immunodulatory derivative (immunomodulatory imide drug \[IMiD\]) agents as well as other therapeutic agents used in this trial are known to be teratogenic. Females of child-bearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10-14 days prior to, and again within 24 hours of starting lenalidomide, and must either commit to continued abstinence from heterosexual intercourse or begin two acceptable methods of birth control, one highly effective method and one additional effective method at the same time, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. All patients must be counselled at a minimum of every 28 days about pregnancy precautions and risk of fetal exposure. Should a woman become pregnant or suspect she is pregnant while she or her partner are participating in this study, she should inform her treating physician immediately. FCBP must use adequate contraception for at least 28 days after discontinuation from study. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for at least 28 days after discontinuation from study
  • Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a legally-authorized representative (LAR) and/or family member available will also be eligible

Exclusion Criteria:

  • Patients that have received prior IMiDs for treatment of ATLL
  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
  • Patients who have not recovered to grade 1 or better from AEs due to prior anti-cancer therapy (not including cycle 1 of EPOCH, CHOP, or CHOPE if received off protocol) within 14 days prior to enrollment, with the exception of alopecia
  • Patients who are receiving any other investigational agents or have received them within 14 days prior to enrollment
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to lenalidomide or other agents used in study. Anaphylactic reactions including death have been reported with cyclophosphamide. Possible cross-sensitivity with other alkylating agents can occur
  • Patients unable to take aspirin or prophylactic doses of low molecular weight heparin or direct oral anticoagulants
  • Patients with urinary outflow obstruction (contraindication for cyclophosphamide)
  • Patients with any form of demyelinating disease should not be given vincristine sulfate injection
  • Patients with uncontrolled intercurrent illness
  • Patients with psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because lenalidomide is an IMiD 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 lenalidomide, breastfeeding should be discontinued if the mother is treated with lenalidomide. These potential risks may also apply to other agents used in this study

Study Design

Enrollment

30 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Treatment (lenalidomide, EPOCH)

See Detailed Description.

Interventions

Biospecimen Collection

Undergo tissue and blood sample collection

Bone Marrow Biopsy

Undergo bone marrow biopsy

Computed Tomography

Undergo PET/CT or CT

Cyclophosphamide

Given IV

Doxorubicin Hydrochloride

Given IV

Echocardiography Test

Undergo ECHO

Etoposide

Given IV

Lenalidomide

Given PO

Multigated Acquisition Scan

Undergo MUGA

Positron Emission Tomography

Undergo PET/CT

Prednisone

Given PO

Vincristine Sulfate

Given IV

Primary outcome measure

  • Maximum tolerated dose (MTD) [ Time Frame: Up to the end of induction therapy ]

Central Contacts and Locations

Locations

Emory University Hospital Midtown

Recruiting

Atlanta, Georgia, United States, 30308

Contacts

Site Public Contact

888-946-7447

Principal Investigator:

Pamela B. Allen

Emory University Hospital/Winship Cancer Institute

Recruiting

Atlanta, Georgia, United States, 30322

Contacts

Site Public Contact

404-778-1868

Principal Investigator:

Pamela B. Allen

Siteman Cancer Center at Saint Peters Hospital

Recruiting

City of Saint Peters, Missouri, United States, 63376

Contacts

Site Public Contact

800-600-3606info@siteman.wustl.edu

Principal Investigator:

Lee Ratner

Siteman Cancer Center at West County Hospital

Recruiting

Creve Coeur, Missouri, United States, 63141

Contacts

Site Public Contact

800-600-3606info@siteman.wustl.edu

Principal Investigator:

Lee Ratner

Washington University School of Medicine

Recruiting

St Louis, Missouri, United States, 63110

Contacts

Site Public Contact

800-600-3606info@siteman.wustl.edu

Principal Investigator:

Lee Ratner

Siteman Cancer Center-South County

Recruiting

St Louis, Missouri, United States, 63129

Contacts

Site Public Contact

800-600-3606info@siteman.wustl.edu

Principal Investigator:

Lee Ratner

Memorial Sloan Kettering Basking Ridge

Recruiting

Basking Ridge, New Jersey, United States, 07920

Contacts

Site Public Contact

212-639-7592

Principal Investigator:

Steven M. Horwitz

Memorial Sloan Kettering Monmouth

Recruiting

Middletown, New Jersey, United States, 07748

Contacts

Site Public Contact

212-639-7592

Principal Investigator:

Steven M. Horwitz

Memorial Sloan Kettering Bergen

Recruiting

Montvale, New Jersey, United States, 07645

Contacts

Site Public Contact

212-639-7592

Principal Investigator:

Steven M. Horwitz

Memorial Sloan Kettering Commack

Recruiting

Commack, New York, United States, 11725

Contacts

Site Public Contact

212-639-7592

Principal Investigator:

Steven M. Horwitz

Memorial Sloan Kettering Westchester

Recruiting

Harrison, New York, United States, 10604

Contacts

Site Public Contact

212-639-7592

Principal Investigator:

Steven M. Horwitz

NYU Langone Hospital - Long Island

Recruiting

Mineola, New York, United States, 11501

Contacts

Site Public Contact

212-263-4432cancertrials@nyulangone.org

Principal Investigator:

Catherine S. Diefenbach

Laura and Isaac Perlmutter Cancer Center at NYU Langone

Recruiting

New York, New York, United States, 10016

Contacts

Site Public Contact

CancerTrials@nyulangone.org

Principal Investigator:

Catherine S. Diefenbach

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

Recruiting

New York, New York, United States, 10032

Contacts

Site Public Contact

212-342-5162cancerclinicaltrials@cumc.columbia.edu

Principal Investigator:

Jennifer E. Amengual

Memorial Sloan Kettering Cancer Center

Recruiting

New York, New York, United States, 10065

Contacts

Site Public Contact

212-639-7592

Principal Investigator:

Steven M. Horwitz

NYP/Weill Cornell Medical Center

Recruiting

New York, New York, United States, 10065

Contacts

Site Public Contact

212-746-1848

Principal Investigator:

Jia Ruan

Memorial Sloan Kettering Nassau

Recruiting

Uniondale, New York, United States, 11553

Contacts

Site Public Contact

212-639-7592

Principal Investigator:

Steven M. Horwitz

Ohio State University Comprehensive Cancer Center

Recruiting

Columbus, Ohio, United States, 43210

Contacts

Site Public Contact

800-293-5066Jamesline@osumc.edu

Principal Investigator:

Jonathan E. Brammer

VCU Massey Comprehensive Cancer Center

Recruiting

Richmond, Virginia, United States, 23298

Contacts

Site Public Contact

804-628-6430CTOclinops@vcu.edu

Principal Investigator:

Bruce O. Hough

More Information

Sponsor

National Cancer Institute (NCI)

Last update posted

Jul 16, 2026

Last verified

Jul, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by National Cancer Institute (NCI) on 2026-07-16.