Lenalidomide and Combination Chemotherapy (DA-EPOCH-R) in Treating Patients With MYC-Associated B-Cell Lymphomas

March 9, 2026 updated by: University of Chicago

Prospective, Multi-center Phase I/II Trial of Lenalidomide and Dose-Adjusted EPOCH-R in MYC-Associated B-Cell Lymphomas

This phase I/II trial studies the side effects and best dose of lenalidomide when given together with combination chemotherapy and to see how well they work in treating patients with v-myc myelocytomatosis viral oncogene homolog (avian) (MYC)-associated B-cell lymphomas. Lenalidomide may stop the growth of B-cell lymphomas by blocking the growth of new blood vessels necessary for cancer growth and by blocking some of the enzymes needed for cell growth. Biological therapies, such as lenalidomide, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as etoposide, prednisone, vincristine sulfate, doxorubicin hydrochloride, cyclophosphamide, 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. Monoclonal antibodies, such as rituximab, may block cancer growth in different ways by targeting certain cells. Giving lenalidomide together with combination chemotherapy may be an effective treatment in patients with B-cell lymphoma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of lenalidomide when added to dose-adjusted (DA)-etoposide, prednisone, vincristine sulfate, doxorubicin hydrochloride, cyclophosphamide, rituximab (EPOCH-R) (hereby termed "DA-EPOCH-RR") in patients with double hit lymphoma (DHL) lymphomas. (Phase I) II. To determine the 1- and 2-year progression free survival (PFS) of DA-EPOCH-RR in patients with DHL lymphomas. (Phase II)

SECONDARY OBJECTIVES:

I. Overall response rate, complete response, and duration of response. II. Quality of life (QOL) measures using standardized scales. III. Toxicity assessment using version 4.0 of the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) criteria.

IV. Overall survival (OS) at 1 and 2 years.

OUTLINE: This is a phase I, dose-escalation study of lenalidomide followed by a phase II study.

INDUCTION PHASE: Patients receive lenalidomide orally (PO) daily on days 1-14. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

DA-EPOCH-R: Patients receive etoposide intravenously (IV) continuously on days 1-4, prednisone PO twice daily (BID) on days 1-5, vincristine sulfate IV continuously on days 1-4, doxorubicin hydrochloride IV continuously on days 1-4, cyclophosphamide IV over 15 minutes on day 5, and rituximab IV over 4 hours on day 1 (per institutional guidelines). Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION PHASE: Patients who are transplantation (hematopoietic stem cell transplant [HSCT])-eligible receive BCNU, etoposide, cytarabine, and melphalan (BEAM)-conditioning regimen followed by autologous (auto)-HSCT or HSCT at the discretion of the treating physician. Patients who do not undergo HSCT in first remission receive lenalidomide maintenance for 12 months.

After completion of study treatment, patients are followed up for every 3 months for 1 year, every 4 months for 1 year, and then periodically for 1 year.

Study Type

Interventional

Enrollment (Actual)

55

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
      • Chicago, Illinois, United States, 60637
        • University of Chicago
      • Decatur, Illinois, United States, 62526
        • Decatur Memorial Hospital Cancer Care Institute
      • Evanston, Illinois, United States, 60201
        • NorthShore University HealthSystem
      • Peoria, Illinois, United States, 61615
        • Illinois Cancer Care
    • Maryland
      • Baltimore, Maryland, United States, 21202
        • University of Maryland

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

  1. B-cell lymphoma with comprehensive immunohistochemistry (IHC) panel establishing lineage (CD20, CD3) and cell of origin (CD10, BCL6 and MUM1) in addition to proliferative/prognostic markers (Ki-67, C-myc and BCL2). DHL will be identified using cytogenetics and/or immunohistochemistry as detailed in section 4.1.2 below.

  2. To define DHL, patients must have evidence of C-myc [defined as: Cytogenetic evidence (FISH or karyotype) of C-myc breaks (Increased copy number in itself is not considered positivity for C-myc) OR Positive IHC defined as >40% of the lymphoma cells staining for C-myc] PLUS either:

    1. Breaks in BCL-2 via cytogenetic studies or
    2. BCL-2 immunopositivity in >70% of lymphoma cells.
  3. Patients are allowed to have received radiotherapy before enrollment if radiation was given to alleviate pain and/or neurologic compromise as long as there remains areas of measurable disease present. Further, at the investigator's discretion and for patients who are unstable, one cycle of R-CHOP is allowed prior to enrollment but no more than one cycle. For purposes of this trial, prednisone or other corticosteroids used for non-lymphomatous conditions will be allowed. In addition, a prior/recent short course (< 2 weeks) of steroids for symptom relief of lymphoma-related symptoms will be allowed.
  4. AST and ALT < 3 x upper limit of normal (ULN), and total bilirubin <1.5 x ULN (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver involvement with NHL or stable chronic liver disease per investigator assessment).
  5. Patients must have adequate renal function by virtue of GFR > 50 ml/minute using Cockroft-Gault formula.
  6. Patients must have adequate bone marrow function (platelets >100,000 and ANC >1,200). Patients with bone marrow involvement are allowed at the investigator's discretion regardless of cytopenias.
  7. ECOG PS 0-2.
  8. Age ≥ 18 years.
  9. All study participants must be registered into the mandatory lenalidomide REMS® program, and be willing and able to comply with the requirements of the REMS® program.
  10. Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the lenalidomide REMS® program. (Please see study schema for further details)
  11. Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin).
  12. Ability to read, understand, and sign a written informed consent approved by each institutional IRB. Alternatively, patients with legal guardians who can read, understand, and sign written informed consent may also enroll.

Exclusion Criteria

  1. Prior therapy for lymphoma
  2. Known CNS involvement
  3. Known HIV positive status
  4. Pregnant females
  5. Burkitt and/or precursor lymphoblastic leukemia/lymphoma.
  6. Prior pomalidomide exposure
  7. Known hypersensitivity to lenalidomide or thalidomide
  8. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
  9. Subjects who have currently active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver involvement with NHL or stable chronic liver disease per investigator assessment).
  10. Treatment with any known non-marketed drug substance or experimental therapy within 4 weeks prior to enrollment, or currently participating in any other interventional clinical study for NHL or any other illness (except observational, prevention, and/or registry trials).
  11. No current malignancy. Subjects who have been free of malignancy for at least 2 years, or have a history of completely resected non-melanoma skin cancer, or successfully treated in situ carcinoma (any site) are eligible. Women with a history of cervical cancers are allowed.
  12. Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active Hepatitis C.
  13. History of significant cerebrovascular disease in the past 3 months or ongoing event with active symptoms or sequelae.
  14. Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA test will be performed and if positive, the subject will be excluded if unable to tolerate and/or receive anti-Hepatitis-B therapy. Positive serology because of prior vaccination is allowed.
  15. Positive serology for hepatitis C (HC) defined as a positive test for HCAb.
  16. Inability to comply with study or follow-up testing and procedures.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (lenalidomide, DA-EPOCH-R)

INDUCTION PHASE: Patients receive lenalidomide PO daily on days 1-14. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

DA-EPOCH-R: Patients receive etoposide IV continuously on days 1-4, prednisone PO BID on days 1-5, vincristine sulfate IV continuously on days 1-4, doxorubicin hydrochloride IV continuously on days 1-4, cyclophosphamide IV over 15 minutes on day 5, and rituximab IV over 4 hours on day 1 (per institutional guidelines). Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION PHASE: Patients who are transplantation (HSCT)-eligible receive BEAM-conditioning regimen followed by autologous (auto)-HSCT or HSCT at the discretion of the treating physician. Patients who do not undergo HSCT in first remission receive lenalidomide maintenance for 12 months.
Drug: lenalidomide
Given PO
Other Names:
  • CC-5013
  • IMiD-1
  • Revlimid
Other: laboratory biomarker analysis
Correlative studies
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • Endoxan
  • CPM
  • CTX
  • Endoxana
Biological: rituximab
Given IV
Other Names:
  • Rituxan
  • Mabthera
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • MOAB IDEC-C2B8
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • Adriamycin PFS
  • Adriamycin RDF
  • ADR
  • Adria
Drug: vincristine sulfate
Given IV
Other Names:
  • VCR
  • leurocristine sulfate
  • Vincasar PFS
Other: quality-of-life assessment
Ancillary studies
Other Names:
  • quality of life assessment
Drug: prednisone
Given PO
Other Names:
  • DeCortin
  • Deltra

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose-limiting Toxicity (Phase I)
Time Frame: Up to 21 days
Number of patients with dose-limiting toxicity (DLT) defined as any grade 4 non-hemaotologic toxicity or any recurrent grade 3 non-hematologic toxicity despite optimal medical management
Up to 21 days
Progression-free Survival
Time Frame: Assessed up to 5 years
Time elapsed between treatment initiation and tumor progression or death from any cause, whichever occurs first.
Assessed up to 5 years
Progression-free Survival at 1 Year
Time Frame: 1 year
The percentage of patients alive and progression-free at 1 year.
1 year
Progression-free Survival at 2 Years
Time Frame: 2 years
Percentage of patients alive and progression-free at 2 years.
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival at 18 Weeks
Time Frame: 18 weeks
Percentage of patients alive and progression-free at 18 weeks.
18 weeks
Overall Response Rate
Time Frame: Up to 18 weeks
Partial response (PR) or complete response (CR) by computed tomography (CT) of positron emission tomography/CT and/or resolution of marrow-only involvement (if originally involved), according to the Revised Response Criteria for Malignant Lymphoma and Cheson et al.
Up to 18 weeks
Anti-tumor Activity
Time Frame: Up to 18 weeks
Stable disease (SD), PR, or CR by computed tomography (CT) of positron emission tomography/CT and/or resolution of marrow-only involvement (if originally involved)according to the Revised Response Criteria for Malignant Lymphoma and Cheson et al.
Up to 18 weeks
Duration of Response (Rate at 2 Years)
Time Frame: 2 years
Percentage of responding patients alive and progression free two years later.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Chicago

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Sonali Smith, University of Chicago

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 29, 2014

Primary Completion (Actual)

October 1, 2024

Study Completion (Actual)

October 29, 2024

Study Registration Dates

First Submitted

August 5, 2014

First Submitted That Met QC Criteria

August 7, 2014

First Posted (Estimated)

August 12, 2014

Study Record Updates

Last Update Posted (Actual)

March 11, 2026

Last Update Submitted That Met QC Criteria

March 9, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 13-1406 (Other Identifier: University of Chicago)
  • P30CA014599 (U.S. NIH Grant/Contract)
  • NCI-2014-01581 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • IRB13-1406

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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