Trial record 2 of 18 for:    DA-EPOCH +/- Rituximab: Lymphoma

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by University of Chicago
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Chicago
ClinicalTrials.gov Identifier:
NCT02213913
First received: August 5, 2014
Last updated: August 14, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of Chicago:

Primary Outcome Measures:
  • PFS [ Time Frame: Time elapsed between treatment initiation and tumor progression or death from any cause (whichever occurs first), assessed up to 3 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
    The occurrence and severity of each event will be recorded.


Estimated Enrollment: 46
Study Start Date: August 2014
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: prednisone
Given PO
Other Names:
  • DeCortin
  • Deltra
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Biological: rituximab
Given IV
Other Names:
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: laboratory biomarker analysis
Correlative studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • B-cell lymphoma with comprehensive immunohistochemistry (IHC) panel establishing lineage (cluster of differentiation [CD]20, CD3) and cell of origin (CD10, B-cell chronic lymphocytic leukemia [CLL]/lymphoma 6 [BCL6] and melanoma associated antigen [mutated] 1 [MUM1]) in addition to proliferative/prognostic markers (proliferation-related Ki-67 antigen [Ki-67], C-myc and B-cell CLL/lymphoma 2 [BCL2]); DHL will be identified using cytogenetics and/or immunohistochemistry as detailed in DHL defined below
  • To define DHL, patients must have evidence of C-myc (defined as: cytogenetic evidence [fluorescence in situ hybridization (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 must have had no prior chemotherapy, radiotherapy, or immunotherapy for lymphoma; for purposes of this trial, prednisone or other corticosteroids used for non-lymphomatous conditions will not be considered as prior chemotherapy; in addition, a prior/recent short course (=< 2 weeks) of steroids for symptom relief of lymphoma-related symptoms will be allowed
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN) (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver involvement with non-Hodgkin lymphoma [NHL] or stable chronic liver disease per investigator assessment)
  • 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)
  • Glomerular filtration rate (GFR) >= 50 ml/minute using Cockroft-Gault formula
  • Platelets >= 100,000; patients with bone marrow involvement are allowed at the investigator's discretion regardless of cytopenias
  • Absolute neutrophil count (ANC) >= 1,200; patients with bone marrow involvement are allowed at the investigator's discretion regardless of cytopenias
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
  • All study participants must be registered into the mandatory lenalidomide Risk Evaluation and Mitigation Strategies (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
  • Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to acetylsalicylic acid [ASA] may use warfarin or low molecular weight heparin)
  • Ability to read, understand, and sign a written informed consent approved by each Institutional Review Board (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 central nervous system (CNS) involvement
  • Known human immunodeficiency virus (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 hepatitis B surface antigen (HBsAg); in addition, if negative for HBsAg but hepatitis B core antibody (HBcAb) positive (regardless of HBsAb status), a HB deoxyribonucleic acid (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 hepatitis C antibody (HCAb)
  • Inability to comply with study or follow-up testing and procedures
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02213913

Locations
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Chadi Nabhan    773-702-9574    cnabhan@medicine.bsd.uchicago.edu   
Principal Investigator: Chadi Nabhan         
Sponsors and Collaborators
University of Chicago
Investigators
Principal Investigator: Chadi Nabhan University of Chicago
  More Information

No publications provided

Responsible Party: University of Chicago
ClinicalTrials.gov Identifier: NCT02213913     History of Changes
Other Study ID Numbers: 13-1406, NCI-2014-01581, IRB13-1406, 13-1406, P30CA014599
Study First Received: August 5, 2014
Last Updated: August 14, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphoma, Mantle-Cell
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Large B-Cell, Diffuse
Lymphoma, B-Cell
Lymphoma, Large-Cell, Immunoblastic
Lymphoma
Lymphoma, Extranodal NK-T-Cell
Intraocular Lymphoma
Lymphoma, T-Cell
Rituximab
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Hodgkin Disease
Leukemia
Waldenstrom Macroglobulinemia
Leukemia, Hairy Cell
Lymphomatoid Granulomatosis
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

ClinicalTrials.gov processed this record on October 16, 2014