Clinical Trial: 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

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

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

Brief Summary: 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.

Detailed Summary:

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
Sponsor: Fred Hutchinson Cancer Research Center

Current Primary Outcome: 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 ]

Estimated using the Kaplan-Meier method in all cohorts.


Original Primary Outcome: 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 ]

Assessed by Kaplan-Meier method.


Current Secondary Outcome:

  • Rate of Response (CR, PR, or SD) and Time to Progression [ Time Frame: Assessed up to 18 months ]
    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 ]
  • 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 ]
  • Comparison of Rates of Overall Response and Complete Remission Between the First, Second, and Third Cohorts [ Time Frame: Assessed up to 18 months ]
  • Changes in Plasma Cytokines and Peripheral Blood Lymphocytes in Correlation to Treatment With Lenalidomide [ Time Frame: From baseline to day 28 of course 3 ]
  • 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 ]
  • 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 ]
  • 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 ]


Original Secondary Outcome:

  • Rate of Response (CR, PR, or SD) and Time to Progression [ Time Frame: Every 2 months at day 1 of courses 1, 3, 5, 7, 9, and 12 and then every 3 months for 18 months ]
  • Grade III-IV Toxicity in Patients Receiving Lenalidomide With or Without Rituximab [ Time Frame: Days 8 and 22 of course 1, day 1 of each subsequent course, and 30 days after completion of study treatment ]
  • Incidences of Grades II-IV Acute GVHD and Limited or Extensive Chronic GVHD [ Time Frame: Days 1 and 22 of course 1, day 1 of each subsequent course, and 30 days after completion of study treamtent ]
  • Comparison of Rates of Overall Response and Complete Remission Between the First, Second, and Third Cohorts [ Time Frame: Every 2 months at day 1 of courses 1, 3, 5, 7, 9, and 12 and then every 3 months for 18 months ]
  • Changes in Plasma Cytokines and Peripheral Blood Lymphocytes in Correlation to Treatment With Lenalidomide [ Time Frame: Baseline, day 7, and day 28 of course 1 and day 28 of course 3 ]
  • Comparison of Incidences of Adverse Events Between the First, Second, and Third Cohorts [ Time Frame: Days 8 and 22 of course 1, day 1 of each subsequent course, and 30 days after completion of study treatment ]
  • Pharmacokinetics of Rituximab: Evaluation of Serum Concentrations and Correlations to Drug Dose and Clinical Responses [ Time Frame: Baseline, day 7, and day 28 of course 1 and day 28 of course 3 ]
  • Donor and Host Polymorphisms of the FCgamma RIIIa Receptor and Their Impact on Disease Response and Relapse [ Time Frame: Baseline, day 7, and day 28 of course 1 and day 28 of course 3 ]


Information By: Fred Hutchinson Cancer Research Center

Dates:
Date Received: August 15, 2011
Date Started: May 2012
Date Completion:
Last Updated: January 31, 2017
Last Verified: January 2017