Lenalidomide and Combination Chemotherapy (DA-EPOCH-R) in Treating Patients With MYC-Associated B-Cell Lymphomas
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| ClinicalTrials.gov Identifier: NCT02213913 |
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Recruitment Status :
Active, not recruiting
First Posted : August 12, 2014
Last Update Posted : October 11, 2021
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Adult Grade III Lymphomatoid Granulomatosis B-cell Chronic Lymphocytic Leukemia Contiguous Stage II Adult Diffuse Large Cell Lymphoma Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma Contiguous Stage II Grade 1 Follicular Lymphoma Contiguous Stage II Grade 2 Follicular Lymphoma Contiguous Stage II Grade 3 Follicular Lymphoma Contiguous Stage II Mantle Cell Lymphoma Contiguous Stage II Marginal Zone Lymphoma Contiguous Stage II Small Lymphocytic Lymphoma Cutaneous B-cell Non-Hodgkin Lymphoma Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue Intraocular Lymphoma Nodal Marginal Zone B-cell Lymphoma Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma Noncontiguous Stage II Grade 1 Follicular Lymphoma Noncontiguous Stage II Grade 2 Follicular Lymphoma Noncontiguous Stage II Grade 3 Follicular Lymphoma Noncontiguous Stage II Mantle Cell Lymphoma Noncontiguous Stage II Marginal Zone Lymphoma Noncontiguous Stage II Small Lymphocytic Lymphoma Progressive Hairy Cell Leukemia, Initial Treatment Small Intestine Lymphoma Splenic Marginal Zone Lymphoma Stage 0 Chronic Lymphocytic Leukemia Stage I Adult Diffuse Large Cell Lymphoma Stage I Adult Diffuse Mixed Cell Lymphoma Stage I Adult Diffuse Small Cleaved Cell Lymphoma Stage I Adult Hodgkin Lymphoma Stage I Adult Immunoblastic Large Cell Lymphoma Stage I Chronic Lymphocytic Leukemia Stage I Grade 1 Follicular Lymphoma Stage I Grade 2 Follicular Lymphoma Stage I Grade 3 Follicular Lymphoma Stage I Mantle Cell Lymphoma Stage I Marginal Zone Lymphoma Stage I Small Lymphocytic Lymphoma Stage II Adult Hodgkin Lymphoma Stage II Chronic Lymphocytic Leukemia Stage II Small Lymphocytic Lymphoma Stage III Adult Diffuse Large Cell Lymphoma Stage III Adult Diffuse Mixed Cell Lymphoma Stage III Adult Diffuse Small Cleaved Cell Lymphoma Stage III Adult Hodgkin Lymphoma Stage III Adult Immunoblastic Large Cell Lymphoma Stage III Chronic Lymphocytic Leukemia Stage III Grade 1 Follicular Lymphoma Stage III Grade 2 Follicular Lymphoma Stage III Grade 3 Follicular Lymphoma Stage III Mantle Cell Lymphoma Stage III Marginal Zone Lymphoma Stage III Small Lymphocytic Lymphoma Stage IV Adult Diffuse Large Cell Lymphoma Stage IV Adult Diffuse Mixed Cell Lymphoma Stage IV Adult Diffuse Small Cleaved Cell Lymphoma Stage IV Adult Hodgkin Lymphoma Stage IV Adult Immunoblastic Large Cell Lymphoma Stage IV Chronic Lymphocytic Leukemia Stage IV Grade 1 Follicular Lymphoma Stage IV Grade 2 Follicular Lymphoma Stage IV Grade 3 Follicular Lymphoma Stage IV Mantle Cell Lymphoma Stage IV Marginal Zone Lymphoma Stage IV Small Lymphocytic Lymphoma Testicular Lymphoma Untreated Hairy Cell Leukemia Waldenström Macroglobulinemia | Drug: lenalidomide Drug: etoposide Drug: prednisone Drug: vincristine sulfate Drug: doxorubicin hydrochloride Drug: cyclophosphamide Biological: rituximab Other: quality-of-life assessment Other: laboratory biomarker analysis | Phase 1 Phase 2 |
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 (Clinical Trial) |
| Estimated Enrollment : | 46 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Prospective, Multi-center Phase I/II Trial of Lenalidomide and Dose-Adjusted EPOCH-R in MYC-Associated B-Cell Lymphomas |
| Actual Study Start Date : | July 29, 2014 |
| Estimated Primary Completion Date : | July 29, 2022 |
| Estimated Study Completion Date : | July 29, 2023 |
| Arm | Intervention/treatment |
|---|---|
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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:
Drug: etoposide Given IV
Other Names:
Drug: prednisone Given PO
Other Names:
Drug: vincristine sulfate Given IV
Other Names:
Drug: doxorubicin hydrochloride Given IV
Other Names:
Drug: cyclophosphamide Given IV
Other Names:
Biological: rituximab Given IV
Other Names:
Other: quality-of-life assessment Ancillary studies
Other Name: quality of life assessment Other: laboratory biomarker analysis Correlative studies |
- PFS [ Time Frame: Time elapsed between treatment initiation and tumor progression or death from any cause (whichever occurs first), assessed up to 3 years ]
- MTD of adding lenalidomide to the DA-EPOCH-R regimen as a front-line therapy in patients with DHL lymphomas (using CTCAE v 4.0) (Phase I) [ Time Frame: Up to 21 days ]
- PFS (Phase II) [ Time Frame: Time elapsed between treatment initiation and tumor progression or death from any cause (whichever occurs first), assessed at 1 year ]
- PFS (Phase II) [ Time Frame: Time elapsed between treatment initiation and tumor progression or death from any cause (whichever occurs first), assessed at 2 years ]
- Add lenalidomide to the DA-EPOCH-R regimen as a front-line therapy in patients with DHL lymphomas (Phase I) [ Time Frame: Up to 18 weeks ]Time elapsed between treatment initiation and tumor progression or death from any cause (whichever occurs first), assessed up to 18 weeks
- Overall response rate defined as the sum of partial response (PR) and complete response (CR) by computed tomography (CT) of positron emission tomography/CT and/or resolution of marrow-only involvement (if originally involved) (Phase I) [ Time Frame: Up to 18 weeks ]
- Anti-tumor activity, calculated as the sum of stable disease, PR, and CR according to the Revised Response Criteria for Malignant Lymphoma and Cheson et al (Phase I) [ Time Frame: Up to 18 weeks ]
- Duration of response, calculated as the duration from detecting any objective response until progression or death from any cause, according to the Revised Response Criteria for Malignant Lymphoma and Cheson et al (Phase I) [ Time Frame: Time elapsed between initial documented PR or CR and first progression event, assessed up to 18 weeks ]
- Incidence of adverse events, defined as the occurrence of all grades of toxicity (using CTCAE version 4.0) [ Time Frame: Up to 21 days from last treatment ]The occurrence and severity of each event will be recorded.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria
- 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.
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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.
Exclusion Criteria
- 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.
- Inability to comply with study or follow-up testing and procedures.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02213913
| United States, Illinois | |
| Rush University Medical Center | |
| Chicago, Illinois, United States, 60612 | |
| University of Chicago | |
| Chicago, Illinois, United States, 60637 | |
| Decatur Memorial Hospital Cancer Care Institute | |
| Decatur, Illinois, United States, 62526 | |
| NorthShore University HealthSystem | |
| Evanston, Illinois, United States, 60201 | |
| Illinois Cancer Care | |
| Peoria, Illinois, United States, 61615 | |
| United States, Maryland | |
| University of Maryland | |
| Baltimore, Maryland, United States, 21202 | |
| Principal Investigator: | Sonali Smith | University of Chicago |
| Responsible Party: | University of Chicago |
| ClinicalTrials.gov Identifier: | NCT02213913 |
| Other Study ID Numbers: |
13-1406 NCI-2014-01581 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) IRB13-1406 13-1406 ( Other Identifier: University of Chicago ) P30CA014599 ( U.S. NIH Grant/Contract ) |
| First Posted: | August 12, 2014 Key Record Dates |
| Last Update Posted: | October 11, 2021 |
| Last Verified: | October 2021 |
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Lymphoma Leukemia Lymphoma, Follicular Lymphoma, Non-Hodgkin Leukemia, Lymphoid Lymphoma, B-Cell Leukemia, Lymphocytic, Chronic, B-Cell Hodgkin Disease Lymphoma, Mantle-Cell Lymphoma, B-Cell, Marginal Zone Lymphoma, Large B-Cell, Diffuse Lymphoma, Large-Cell, Immunoblastic Plasmablastic Lymphoma Waldenstrom Macroglobulinemia Leukemia, Hairy Cell |
Lymphomatoid Granulomatosis Intraocular Lymphoma Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Leukemia, B-Cell Neoplasms, Plasma Cell Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders |