Testing the Addition of an Anti-cancer Drug, Lenalidomide, to the Usual Combination Chemotherapy Treatment ("EPOCH") for Adult T-Cell Leukemia-Lymphoma (ATLL)

NCT ID: NCT04301076

Last Updated: 2026-01-22

Basic Information

• Recruitment Status: SUSPENDED
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-31
• Study Completion Date: 2027-06-30

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.

Detailed Description

PRIMARY OBJECTIVE:

I. To determine the safest and most tolerable dose and schedule of lenalidomide to combine with etoposide, prednisone, vincristine sulfate (Oncovin), cyclophosphamide, and doxorubicin hydrochloride (hydroxydaunorubicin hydrochloride) (EPOCH) chemotherapy in adult T-cell leukemia-lymphoma (ATL/ATLL).

SECONDARY OBJECTIVES:

I. To observe and record anti-tumor activity. II. To determine if lenalidomide and EPOCH activity results in significant improvement in remission rates, duration of remissions, and overall survival (OS) as compared to historical controls.

III. To determine if lenalidomide and EPOCH activity correlates with T-cell receptor (TCR) pathway gene mutational spectrum.

IV. To determine effects of lenalidomide and EPOCH on human T-cell leukemia virus type 1 (HTLV-1) proviral deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) loads.

V. To determine effects of lenalidomide and EPOCH on HTLV-1 clonality.

OUTLINE: This is a dose-escalation study of lenalidomide followed by a dose-expansion study.

INDUCTION THERAPY: Patients receive lenalidomide orally (PO) once daily (QD) on days 1-14 of 21 day cycles or days 1-21 or 1-28 of 28 day cycles. Patients receive doxorubicin hydrochloride intravenously (IV) continuously on days 1-4, vincristine sulfate IV continuously on days 1-4, etoposide IV continuously on days 1-4, prednisone PO on days 1-5, and cyclophosphamide IV over 1-4 hours on day 5. Treatment repeats every 21 or 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients with complete response (CR), partial response (PR), or stable disease (SD) may receive up to 2 additional cycles of lenalidomide, doxorubicin hydrochloride, vincristine sulfate, etoposide, prednisone, and cyclophosphamide at the discretion of the investigator and/or up to an additional 2 years of lenalidomide in the absence of disease progression or unacceptable toxicity.

Patients undergo bone marrow biopsy at baseline and as clinically indicated. Patients undergo positron emission tomography/computed tomography (PET/CT) or CT, tissue and blood sample collection throughout the trial.

After completion of study treatment, patients are followed up for 2 years from end of induction. Patients who do not continue on lenalidomide maintenance are followed every 3 months for up to 2 years from the end of induction, progression, withdrawal, or until death, whichever occurs first.

Conditions

Acute Adult T-Cell Leukemia/Lymphoma; Adult T-Cell Leukemia/Lymphoma; Chronic Adult T-Cell Leukemia/Lymphoma; HTLV-1 Infection

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (lenalidomide, EPOCH)

INDUCTION THERAPY: Patients receive lenalidomide PO QD on days 1-14 of 21 day cycles or days 1-21 or 1-28 of 28 day cycles. Patients receive doxorubicin hydrochloride IV continuously on days 1-4, vincristine sulfate IV continuously on days 1-4, etoposide IV continuously on days 1-4, prednisone PO on days 1-5, and cyclophosphamide IV over 1-4 hours on day 5. Treatment repeats every 21 or 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients with CR, PR, or SD may receive up to 2 additional cycles of lenalidomide, doxorubicin hydrochloride, vincristine sulfate, etoposide, prednisone, and cyclophosphamide at the discretion of the investigator and/or up to an additional 2 years of lenalidomide in the absence of disease progression or unacceptable toxicity.

Patients undergo bone marrow biopsy at baseline and as clinically indicated. Patients undergo PET/CT or CT, tissue and blood sample collection throughout.

Group Type: EXPERIMENTAL

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo tissue and blood sample collection

Bone Marrow Biopsy

Intervention Type: PROCEDURE

Undergo bone marrow biopsy

Computed Tomography

Intervention Type: PROCEDURE

Undergo PET/CT or CT

Cyclophosphamide

Intervention Type: DRUG

Given IV

Doxorubicin Hydrochloride

Intervention Type: DRUG

Given IV

Etoposide

Intervention Type: DRUG

Given IV

Lenalidomide

Intervention Type: DRUG

Given PO

Positron Emission Tomography

Intervention Type: PROCEDURE

Undergo PET/CT

Prednisone

Intervention Type: DRUG

Given PO

Vincristine Sulfate

Intervention Type: DRUG

Given IV

Interventions

Biospecimen Collection

Undergo tissue and blood sample collection

Intervention Type: PROCEDURE

Bone Marrow Biopsy

Undergo bone marrow biopsy

Intervention Type: PROCEDURE

Computed Tomography

Undergo PET/CT or CT

Intervention Type: PROCEDURE

Cyclophosphamide

Given IV

Intervention Type: DRUG

Doxorubicin Hydrochloride

Given IV

Intervention Type: DRUG

Etoposide

Given IV

Intervention Type: DRUG

Lenalidomide

Given PO

Intervention Type: DRUG

Positron Emission Tomography

Undergo PET/CT

Intervention Type: PROCEDURE

Prednisone

Given PO

Intervention Type: DRUG

Vincristine Sulfate

Given IV

Intervention Type: DRUG

Other Intervention Names

Biological Sample Collection; Biospecimen Collected; Specimen Collection; Biopsy of Bone Marrow; Biopsy, Bone Marrow; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized axial tomography (procedure); Computerized Tomography; Computerized Tomography (CT) scan; CT; CT Scan; Diagnostic CAT Scan; Diagnostic CAT Scan Service Type; tomography; (-)-Cyclophosphamide; 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate; Asta B 518; B 518; B-518; B518; Carloxan; Ciclofosfamida; Ciclofosfamide; Cicloxal; Clafen; Claphene; CP monohydrate; CTX; CYCLO-cell; Cycloblastin; Cycloblastine; Cyclophospham; Cyclophosphamid monohydrate; Cyclophosphamide Monohydrate; Cyclophosphamidum; Cyclophosphan; Cyclophosphane; Cyclophosphanum; Cyclostin; Cyclostine; Cytophosphan; Cytophosphane; Cytoxan; Fosfaseron; Genoxal; Genuxal; Ledoxina; Mitoxan; Neosar; Revimmune; Syklofosfamid; WR 138719; WR- 138719; WR-138719; WR138719; 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI); ADM; Adriacin; Adriamycin; Adriamycin Hydrochloride; Adriamycin PFS; Adriamycin RDF; ADRIAMYCIN, HYDROCHLORIDE; Adriamycine; Adriblastina; Adriblastine; Adrimedac; Chloridrato de Doxorrubicina; DOX; DOXO-CELL; Doxolem; Doxorubicin HCl; Doxorubicin.HCl; Doxorubin; Farmiblastina; FI 106; FI-106; FI106; hydroxydaunorubicin; Rubex; Demethyl Epipodophyllotoxin Ethylidine Glucoside; EPEG; Lastet; Toposar; Vepesid; VP 16; VP 16-213; VP 16213; VP-16; VP-16-213; VP-16213; VP16; VP16213; CC 5013; CC-5013; CC5013; CDC 501; Revlimid; Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron emission tomography (procedure); Positron Emission Tomography Scan; Positron-Emission Tomography; PT; .delta.1-Cortisone; 1, 2-Dehydrocortisone; Adasone; Cortancyl; Dacortin; DeCortin; Decortisyl; Decorton; Delta 1-Cortisone; Delta-Dome; Deltacortene; Deltacortisone; Deltadehydrocortisone; Deltasone; Deltison; Deltra; Econosone; Lisacort; Meprosona-F; Metacortandracin; Meticorten; Ofisolona; Orasone; Panafcort; Panasol-S; Paracort; Perrigo Prednisone; PRED; Predicor; Predicorten; Prednicen-M; Prednicort; Prednidib; Prednilonga; Predniment; Prednisone Intensol; Prednisonum; Prednitone; Promifen; Rayos; Servisone; SK-Prednisone; Kyocristine; Leurocristine Sulfate; Leurocristine, sulfate; Oncovin; Vincasar; Vincosid; Vincrex; Vincristine, sulfate

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lee Ratner

Role: PRINCIPAL_INVESTIGATOR

Yale University Cancer Center LAO

Locations

Emory University Hospital Midtown

Atlanta, Georgia, United States

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, United States

Siteman Cancer Center at Saint Peters Hospital

City of Saint Peters, Missouri, United States

Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri, United States

Washington University School of Medicine

St Louis, Missouri, United States

Siteman Cancer Center-South County

St Louis, Missouri, United States

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, United States

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, United States

Memorial Sloan Kettering Bergen

Montvale, New Jersey, United States

Memorial Sloan Kettering Commack

Commack, New York, United States

Memorial Sloan Kettering Westchester

Harrison, New York, United States

NYU Langone Hospital - Long Island

Mineola, New York, United States

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, United States

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

New York, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

NYP/Weill Cornell Medical Center

New York, New York, United States

Memorial Sloan Kettering Nassau

Uniondale, New York, United States

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

VCU Massey Comprehensive Cancer Center

Richmond, Virginia, United States

Countries

United States

Other Identifiers

NCI-2020-01535

Identifier Type: REGISTRY

Identifier Source: secondary_id

10335

Identifier Type: OTHER

Identifier Source: secondary_id

10335

Identifier Type: OTHER

Identifier Source: secondary_id

UM1CA186689

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UM1CA186704

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2020-01535

Identifier Type: -

Identifier Source: org_study_id