Lenalidomide and Combination Chemotherapy (DA-EPOCH-R) in Treating Patients With MYC-Associated B-Cell Lymphomas
Prospective, Multi-center Phase I/II Trial of Lenalidomide and Dose-Adjusted EPOCH-R in MYC-Associated B-Cell Lymphomas
4 other identifiers
interventional
55
1 country
6
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Jul 2014
Longer than P75 for phase_1
6 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 29, 2014
CompletedFirst Submitted
Initial submission to the registry
August 5, 2014
CompletedFirst Posted
Study publicly available on registry
August 12, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
October 29, 2024
CompletedResults Posted
Study results publicly available
March 11, 2026
CompletedMarch 11, 2026
March 1, 2026
10.2 years
August 5, 2014
September 9, 2025
March 9, 2026
Conditions
Outcome Measures
Primary Outcomes (4)
Dose-limiting Toxicity (Phase I)
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 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
The percentage of patients alive and progression-free at 1 year.
1 year
Progression-free Survival at 2 Years
Percentage of patients alive and progression-free at 2 years.
2 years
Secondary Outcomes (4)
Progression-free Survival at 18 Weeks
18 weeks
Overall Response Rate
Up to 18 weeks
Anti-tumor Activity
Up to 18 weeks
Duration of Response (Rate at 2 Years)
2 years
Study Arms (1)
Treatment (lenalidomide, DA-EPOCH-R)
EXPERIMENTALINDUCTION 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.
Interventions
Given PO
Given IV
Given IV
Given IV
Ancillary studies
Given IV
Eligibility Criteria
You may qualify if:
- 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.
- 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:
- Breaks in BCL-2 via cytogenetic studies or
- BCL-2 immunopositivity in \>70% of lymphoma cells.
- 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.
- 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).
- Patients must have adequate renal function by virtue of GFR \> 50 ml/minute using Cockroft-Gault formula.
- 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.
- ECOG PS 0-2.
- Age ≥ 18 years.
- 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.
- 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)
- Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin).
- 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.
You may not qualify if:
- Prior therapy for lymphoma
- Known CNS involvement
- Known HIV positive status
- Pregnant females
- Burkitt and/or precursor lymphoblastic leukemia/lymphoma.
- Prior pomalidomide exposure
- Known hypersensitivity to lenalidomide or thalidomide
- The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
- 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).
- 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).
- 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.
- 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.
- History of significant cerebrovascular disease in the past 3 months or ongoing event with active symptoms or sequelae.
- 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.
- Positive serology for hepatitis C (HC) defined as a positive test for HCAb.
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Chicagolead
- National Cancer Institute (NCI)collaborator
Study Sites (6)
Rush University Medical Center
Chicago, Illinois, 60612, United States
University of Chicago
Chicago, Illinois, 60637, United States
Decatur Memorial Hospital Cancer Care Institute
Decatur, Illinois, 62526, United States
NorthShore University HealthSystem
Evanston, Illinois, 60201, United States
Illinois Cancer Care
Peoria, Illinois, 61615, United States
University of Maryland
Baltimore, Maryland, 21202, United States
Related Publications (1)
Cahill K, Godfrey J, Nabhan C, Kline J, Riedell PA, Cohen KS, Narula S, Karrison TG, Robertson J, Karmali R, Venugopal P, Kim SH, Rapoport AP, Lee ST, Law J, Fishkin PAS, Isufi I, Velasco M, Kaminer L, Smith SM. A multicenter phase 1/2 trial of lenalidomide and dose-adjusted EPOCH-R in MYC-associated DLBCL. Blood Adv. 2025 Nov 11;9(21):5665-5675. doi: 10.1182/bloodadvances.2025017092.
PMID: 40720747DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Research Professor
- Organization
- University of Chicago
Study Officials
- PRINCIPAL INVESTIGATOR
Sonali Smith
University of Chicago
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 5, 2014
First Posted
August 12, 2014
Study Start
July 29, 2014
Primary Completion
October 1, 2024
Study Completion
October 29, 2024
Last Updated
March 11, 2026
Results First Posted
March 11, 2026
Record last verified: 2026-03