Lenalidomide With or Without Rituximab in Treating Patients With Progressive or Relapsed Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Prolymphocytic Leukemia, or Non-Hodgkin Lymphoma Previously Treated With Donor Stem Cell Transplant

This study has been terminated.
(Low accrual)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT01419795
First received: August 15, 2011
Last updated: April 3, 2014
Last verified: April 2014
  Purpose

This phase II trial studies how well giving lenalidomide with or without rituximab works in treating patients with progressive or relapsed chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), prolymphocytic leukemia (PLL), or non-Hodgkin lymphoma (NHL). Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving lenalidomide together with or without rituximab may kill more cancer cells.


Condition Intervention Phase
Adult Nasal Type Extranodal NK/T-cell Lymphoma
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-cell Lymphoma
Cutaneous B-cell Non-Hodgkin Lymphoma
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Hepatosplenic T-cell Lymphoma
Intraocular Lymphoma
Nodal Marginal Zone B-cell Lymphoma
Noncutaneous Extranodal Lymphoma
Peripheral T-cell Lymphoma
Prolymphocytic Leukemia
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Adult Grade III Lymphomatoid Granulomatosis
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Adult T-cell Leukemia/Lymphoma
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Mycosis Fungoides/Sezary Syndrome
Recurrent Small Lymphocytic Lymphoma
Refractory Chronic Lymphocytic Leukemia
Refractory Hairy Cell Leukemia
Small Intestine Lymphoma
Splenic Marginal Zone Lymphoma
T-cell Large Granular Lymphocyte Leukemia
Testicular Lymphoma
Waldenström Macroglobulinemia
Drug: lenalidomide
Biological: rituximab
Other: pharmacological study
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study Investigating Treatment of Post-Allogeneic Transplant Progression or Relapse of CLL/SLL/PLL or NHL With Lenalidomide Alone or With Rituximab

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Improvement in overall survival of patients receiving lenalidomide with or without rituximab in comparison to historical controls managed by single or multiple chemotherapeutic agents or donor lymphocyte infusion (DLI) (Cohort 1) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method in all cohorts.


Secondary Outcome Measures:
  • Rate of response (CR, PR, or SD) and time to progression [ Time Frame: Assessed up to 18 months ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method in all cohorts.

  • Grade III-IV toxicity in patients receiving lenalidomide with or without rituximab [ Time Frame: Assessed up to 30 days after completion of study treatment ] [ Designated as safety issue: Yes ]
  • Incidences of grades II-IV acute GVHD and limited or extensive chronic GVHD [ Time Frame: Assessed up to 30 days after completion of study treatment ] [ Designated as safety issue: No ]
  • Comparison of rates of overall response and complete remission between the first, second, and third cohorts [ Time Frame: Assessed up to 18 months ] [ Designated as safety issue: No ]
  • Changes in plasma cytokines and peripheral blood lymphocytes in correlation to treatment with lenalidomide [ Time Frame: From baseline to day 28 of course 3 ] [ Designated as safety issue: No ]
  • Comparison of incidences of adverse events between the first, second, and third cohorts [ Time Frame: Assessed up to 30 days after completion of study treatment ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics of rituximab: evaluation of serum concentrations and correlations to drug dose and clinical responses [ Time Frame: Baseline, day 7 and 28 of course 1, and day 28 of course 3 ] [ Designated as safety issue: No ]
  • Donor and host polymorphisms of the FCgamma RIIIa receptor and their impact on disease response and relapse [ Time Frame: Baseline, day 7 and 28 of course 1, and day 28 of course 3 ] [ Designated as safety issue: No ]

Enrollment: 3
Study Start Date: May 2012
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (lenalidomide, rituximab)
Patients who have relapsed/progressed within 180 days post-transplant (Cohort 1), beyond day 180 post-transplant (Cohort 2), or within 6 months but were not started within 3 months of relapse, receive lenalidomide PO QD on days 1-28 (patients with CLL/SLL/PLL) or days 1-21 (patients with NHL). Patients in Cohorts 1 and 2 also receive rituximab IV on days 1, 8, 15, and 22 of course 1 and then every two months for courses 3, 5, 7, 9, and 11.
Drug: lenalidomide
Given PO
Other Names:
  • CC-5013
  • IMiD-1
  • Revlimid
Biological: rituximab
Given IV
Other Names:
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies
Active Comparator: Arm II (lenalidomide)
Patients who have relapsed/progressed at any time point post-transplant and who have contraindications, prior severe hypersensitivity reaction to rituximab infusion, to receive rituximab or have CD20 negative disease (Cohort 3) receive lenalidomide as in Arm I.
Drug: lenalidomide
Given PO
Other Names:
  • CC-5013
  • IMiD-1
  • Revlimid
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To improve overall survival in patients with relapse of NHL or CLL/SLL/PLL within 180 days after allogeneic hematopoietic cell transplant (HCT).

SECONDARY OBJECTIVES:

I. Rate of response (complete response [CR], partial response [PR], or stable disease [SD]) and time to progression.

II. Grade III-IV toxicity.

III. Incidences of grades II-IV acute graft-versus-host disease (GVHD) and limited or extensive chronic GVHD.

IV. Compare efficacy and safety between the first, second and third cohorts.

V. Laboratory research studies for efficacy and toxicity: blood samples will be stored at baseline, day 7, and day 28 of cycle 1 and day 28 of cycle 3 to investigate:

  1. changes in plasma cytokines and peripheral blood lymphocytes in correlation to treatment with lenalidomide;
  2. pharmacokinetics of rituximab;
  3. donor and host polymorphisms of the FCgamma RIIIa receptor and their impact on disease response and relapse.

OUTLINE: Patients are assigned to 1 of 2 treatment arms.

ARM I: Patients who have relapsed/progressed within 180 days post-transplant (Cohort 1), beyond day 180 post-transplant (Cohort 2), or within 6 months but were not started within 3 months of relapse, receive lenalidomide orally (PO) once daily (QD) on days 1-28 (patients with CLL/SLL/PLL) or days 1-21 (patients with NHL). Patients in Cohorts 1 and 2 also receive rituximab intravenously (IV) on days 1, 8, 15, and 22 of course 1 and then every two months for courses 3, 5, 7, 9, and 11.

ARM II: Patients who have relapsed/progressed at any time point post-transplant and who have contraindications, prior severe hypersensitivity reaction to rituximab infusion, to receive rituximab or have CD20 negative disease (Cohort 3) receive lenalidomide as in Arm I.

Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 and 60 days and then every 3 months for up to 18 months.

  Eligibility

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

Inclusion Criteria:

  • Understand and voluntarily sign an informed consent form
  • Able to adhere to the study visit schedule and other protocol requirements
  • Patients with CLL/SLL/PLL or NHL and who:

    • Met the criteria of relapse or progression after allogeneic HCT according to the HCT protocol or the attending discretion and who,
    • Not responding to appropriate tapering of immunosuppressive medications
  • Absolute neutrophil count (ANC) >= 1500/mm^3 or >= 1000/mm^3 if ANC has persistently < 1500/ mm^3 for more than 2 weeks
  • Platelet count (transfusion independent) >= 50,000/mm^3 or >= 20,000/mm^3 if platelet count has persistently < 50,000/mm^3 for more than 2 weeks
  • Creatinine clearance >= 30ml/min by Cockcroft-Gault formula
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) or =< 3 x ULN if total bilirubin has been persistently > 1.5 x ULN for more than 2 weeks
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine transaminase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 3 x ULN or =< 5 x ULN if AST or ALT have been persistently > 3 x ULN for more than 2 weeks
  • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days and again within 24 hours prior to prescribing lenalidomide for Cycle 1 (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy
  • All study participants must be registered into the mandatory RevAssist program, and be willing and able to comply with the requirements of RevAssist
  • Study participants with risk factors for venous thrombo-embolism (VTE), such as previous VTE, cardiac disease, chronic renal insufficiency, and/or poorly controlled diabetes, should be able to comply with some degree of prophylactic anticoagulation using aspirin 81 or 325 mg daily, coumadin, or low molecular weight heparin

Exclusion Criteria:

  • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from signing the informed consent form
  • Pregnant or breast feeding females; (lactating females must agree not to breast feed while taking lenalidomide)
  • Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
  • Known hypersensitivity to thalidomide
  • The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs
  • Resistance to prior use of lenalidomide, defined as progression on full dose lenalidomide within the first two cycles of therapy
  • Concurrent use of other anti-cancer agents or treatments
  • Known seropositive for or active viral infection with human immunodeficiency virus
  • Karnofsky performance status < 50%
  • Active grades III or IV acute graft-versus-host disease (GVHD)
  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: NCT01419795

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: Mohamed Sorror Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT01419795     History of Changes
Other Study ID Numbers: 2467.00, NCI-2011-01703, P30CA015704
Study First Received: August 15, 2011
Last Updated: April 3, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Burkitt Lymphoma
Immunoblastic Lymphadenopathy
Intraocular Lymphoma
Leukemia
Leukemia, Hairy Cell
Leukemia, Large Granular Lymphocytic
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Leukemia, Prolymphocytic
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Lymphoma
Lymphoma, B-Cell
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Extranodal NK-T-Cell
Lymphoma, Follicular
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Large-Cell, Anaplastic
Lymphoma, Large-Cell, Immunoblastic
Lymphoma, Mantle-Cell
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Lymphoma, T-Cell, Peripheral
Lymphomatoid Granulomatosis
Mycosis Fungoides
Sezary Syndrome
Waldenstrom Macroglobulinemia
Blood Protein Disorders
Cardiovascular Diseases

ClinicalTrials.gov processed this record on October 21, 2014