Recruitment

Recruitment Status
Recruiting

Inclusion Criteria

BCL-2 immunopositivity in >70% of lymphoma cells.
Age ≥ 18 years.
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.
...
BCL-2 immunopositivity in >70% of lymphoma cells.
Age ≥ 18 years.
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.
Patients must have adequate renal function by virtue of GFR > 50 ml/minute using Cockroft-Gault formula.
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).
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)
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.
Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin).
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.
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.
Breaks in BCL-2 via cytogenetic studies or
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.

Exclusion Criteria

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.
Prior pomalidomide exposure
Known CNS involvement
...
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.
Prior pomalidomide exposure
Known CNS involvement
Inability to comply with study or follow-up testing and procedures.
Prior therapy for lymphoma
Pregnant females
Burkitt and/or precursor lymphoblastic leukemia/lymphoma.
The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
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.
Known hypersensitivity to lenalidomide or thalidomide
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).
Known HIV positive status
Positive serology for hepatitis C (HC) defined as a positive test for HCAb.
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).
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.

Summary

Conditions
  • Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma
  • Adult Grade III Lymphomatoid Granulomatosis
  • B Cell Chronic Lymphocytic Leukemia
  • Contiguous Stage II Adult Diffuse Large Cell Lymphoma
  • Testicular Lymphoma
  • Stage IV Chronic Lymphocytic Leukemia
  • Stage IV Grade 1 Follicular Lymphoma
  • Stage I Adult Immunoblastic Large Cell Lymphoma
  • Stage III Adult Diffuse Small Cleaved Cell Lymphoma
  • Stage III Grade 3 Follicular Lymphoma
  • Nodal Marginal Zone B-cell Lymphoma
  • Stage I Grade 2 Follicular Lymphoma
  • Noncontiguous Stage II Grade 2 Follicular Lymphoma
  • Contiguous Stage II Small Lymphocytic Lymphoma
  • Stage I Chronic Lymphocytic Leukemia
  • Stage IV Adult Diffuse Large Cell Lymphoma
  • Stage IV Adult Diffuse Small Cleaved Cell Lymphoma
  • Stage I Adult Diffuse Mixed Cell Lymphoma
  • Stage III Grade 1 Follicular Lymphoma
  • Noncontiguous Stage II Mantle Cell Lymphoma
  • Stage I Grade 1 Follicular Lymphoma
  • Stage IV Small Lymphocytic Lymphoma
  • Waldenstrom Macroglobulinemia
  • Stage II Adult Hodgkin Lymphoma
  • Stage II Small Lymphocytic Lymphoma
  • Stage IV Mantle Cell Lymphoma
  • Stage I Grade 3 Follicular Lymphoma
  • Noncontiguous Stage II Marginal Zone Lymphoma
  • Intraocular Lymphoma
  • Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma
  • Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma
  • Stage III Grade 2 Follicular Lymphoma
  • Stage III Adult Diffuse Mixed Cell Lymphoma
  • Noncontiguous Stage II Grade 3 Follicular Lymphoma
  • Stage IV Adult Hodgkin Lymphoma
  • Stage III Marginal Zone Lymphoma
  • Stage IV Marginal Zone Lymphoma
  • Progressive Hairy Cell Leukemia, Initial Treatment
  • Stage II Chronic Lymphocytic Leukemia
  • Noncontiguous Stage II Small Lymphocytic Lymphoma
  • Contiguous Stage II Grade 1 Follicular Lymphoma
  • Contiguous Stage II Grade 2 Follicular Lymphoma
  • Stage I Marginal Zone Lymphoma
  • Stage III Small Lymphocytic Lymphoma
  • Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma
  • Noncontiguous Stage II Grade 1 Follicular Lymphoma
  • Stage I Adult Diffuse Large Cell Lymphoma
  • Stage IV Adult Diffuse Mixed Cell Lymphoma
  • Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma
  • Stage IV Adult Immunoblastic Large Cell Lymphoma
  • Stage III Chronic Lymphocytic Leukemia
  • Stage IV Grade 2 Follicular Lymphoma
  • Stage I Adult Diffuse Small Cleaved Cell Lymphoma
  • Untreated Hairy Cell Leukemia
  • Stage III Adult Hodgkin Lymphoma
  • Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma
  • Contiguous Stage II Grade 3 Follicular Lymphoma
  • Cutaneous B-cell Non-Hodgkin Lymphoma
  • Stage III Adult Diffuse Large Cell Lymphoma
  • Stage III Mantle Cell Lymphoma
  • Stage I Small Lymphocytic Lymphoma
  • Contiguous Stage II Mantle Cell Lymphoma
  • Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
  • Splenic Marginal Zone Lymphoma
  • Stage I Mantle Cell Lymphoma
  • Stage IV Grade 3 Follicular Lymphoma
  • Small Intestine Lymphoma
  • Stage I Adult Hodgkin Lymphoma
  • Stage III Adult Immunoblastic Large Cell Lymphoma
  • Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma
  • Contiguous Stage II Marginal Zone Lymphoma
  • Stage 0 Chronic Lymphocytic Leukemia
Type
Interventional
Phase
Phase 1 & Phase 2
Design
  • Allocation: N/A
  • Intervention Model: Single Group Assignment
  • Masking: None (Open Label)
  • Primary Purpose: Treatment

Participation Requirements

Age
Between 18 years and 125 years
Gender
Both males and females

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) ...

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.

Inclusion Criteria

BCL-2 immunopositivity in >70% of lymphoma cells.
Age ≥ 18 years.
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.
...
BCL-2 immunopositivity in >70% of lymphoma cells.
Age ≥ 18 years.
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.
Patients must have adequate renal function by virtue of GFR > 50 ml/minute using Cockroft-Gault formula.
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).
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)
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.
Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin).
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.
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.
Breaks in BCL-2 via cytogenetic studies or
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.

Exclusion Criteria

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.
Prior pomalidomide exposure
Known CNS involvement
...
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.
Prior pomalidomide exposure
Known CNS involvement
Inability to comply with study or follow-up testing and procedures.
Prior therapy for lymphoma
Pregnant females
Burkitt and/or precursor lymphoblastic leukemia/lymphoma.
The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
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.
Known hypersensitivity to lenalidomide or thalidomide
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).
Known HIV positive status
Positive serology for hepatitis C (HC) defined as a positive test for HCAb.
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).
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.

Locations

Peoria, Illinois, 61615
Evanston, Illinois, 60201
Chicago, Illinois, 60612
Chicago, Illinois, 60637
Decatur, Illinois, 62526
...
Peoria, Illinois, 61615
Evanston, Illinois, 60201
Chicago, Illinois, 60612
Chicago, Illinois, 60637
Decatur, Illinois, 62526
Baltimore, Maryland, 21202

Tracking Information

NCT #
NCT02213913
Collaborators
National Cancer Institute (NCI)
Investigators
  • Principal Investigator: Sonali Smith University of Chicago
  • Sonali Smith University of Chicago