Study of Lenalidomide in Combination With RICE With Lenalidomide Maintenance Post-Auto Transplant for DLBCL

This study is currently recruiting participants.
Verified November 2010 by Hackensack University Medical Center

First Received on November 15, 2010.  
No Changes Posted
This Clinical Trial Sponsored By: Hackensack University Medical Center
Collaborator: Celgene Corporation
Information provided by: Hackensack University Medical Center
ClinicalTrials.gov Identifier: NCT01241734
 

Purpose for Clinical Trial

The standard of care therapy for DLBCL in the relapsed setting is RICE with the plan for the patient to proceed to transplant. This protocol will add Revlimid to the first 7 days of the RICE therapy and again after transplant as maintenance. To improve over all outcome and survival.

Hypothesis is that combining lenalidomide with standard of care (RICE) may increase overall response rate thus increasing the number of patients able to proceed with autologous stem cell transplant. This in turn may translate into improved overall survival and progression free survival.

Condition Study Intervention Clinical Trial Phase
Diffuse Large B-cell Lymphoma. Drug: Revlimid Phase 1
Phase 2

Study Type: Study Interventional
Study Design: Study Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phae I/II Study of Lenalidomide in Combination With Rituximab, Ifosfamide, Etoposide, and Carboplatin (RICER) as Salvage Therapy With Single Agent Lenalidomide as Maintenance Therapy Post-Autologous Stem Cell Transplantation for the Treatment of Diffuse Large B-Cell Lymphoma (DLBCL) Patients in First Relapse

Resource links provided by NLM:

MedlinePlus related topics:
Lymphoma
Drug Information available for:
Lenalidomide

U.S. FDA Resources

Further study details as provided by Hackensack University Medical Center:

Primary Outcome Measures For Clinical Trial:

  • Stage 1 – Safety (type, frequency, severity and relationship of adverse events to study treatment) and tolerability [ Designated as safety issue: Yes ]
  • Stage 1 – Overall response rate (CR, PR, SD) [ Designated as safety issue: Yes ]
  • Stage 2 – Proportion of patients with a stem cell collection of at least 3×106 CD34+ cells prior to ASCT [ Designated as safety issue: Yes ]
  • Stage 3 – Overall response rate (CR, PR, SD) and complete response rate, and conversion to higher quality of response during maintenance (e.g. from PR to CR) [ Designated as safety issue: Yes ]

Secondary Outcome Measures For Clinical Trial:

  • Stage 2 • Incidence of DLT for determination of MTD to be used in Stage II conversion to higher quality of response during maintenance (e.g. from PR to CR) [ Designated as safety issue: Yes ]
  • Stage 2 – 1 and 2 Year Progression Free Survival (PFS) [ Designated as safety issue: Yes ]
  • Stage 2 – 1 and 2 year Overall Survival (OS) [ Designated as safety issue: Yes ]
  • Stage 2 – Proportion of patients proceeding to stem cell collection and ASCT [ Designated as safety issue: Yes ]
  • Stage 2 – Treatment related adverse events [ Designated as safety issue: Yes ]
  • Stage 3 – Evaluate PFS at 2 yrs post transplant [ Designated as safety issue: Yes ]
  • Stage 3 – Evaluate Overall survival at 2 yrs post transplant [ Designated as safety issue: Yes ]

Estimated Enrollment: 67
Study Start Date: June 2010
Estimated Study Completion Date: October 2012
Estimated Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Study Intervention Details:

    Drug: Revlimid

    Stage I:

    Cohort 1: RICE + Lenalidomide 10mg days 1-7 Cohort 2: RICE + Lenalidomide 15mg days 1-7 Cohort 3: RICE + Lenalidomide 20mg days 1-7 Cohort 4: RICE + Lenalidomide 25mg days 1-7

    Stage III:

    Lenalidomide 25mg days 1-21 every 28 days

    Other Name: Lenalidomide

Detailed Description:

This is a single-institution, 3-Stage, phase I/II, single-arm, open-label study. The first and second stage of the study will assess the safety and efficacy of lenalidomide, rituximab, Ifosfamide, etoposide, and carboplatin (RICER) for the treatment of DLBCL patients in first relapse. The third stage of the study will assess the safety and efficacy of post-ASCT lenalidomide maintenance in patients with DLBC.

In stage I of the study, escalating doses of lenalidomide (10, 15, 20, and 25 mg daily x 7 days on Days 1-7) along with RICE therapy will be given to cohorts of subjects in a standard 3+3 design (see section 5.4.2 for dose escalation schema) until the maximum tolerated dose (MTD) has been determined.

In stage II, all subjects will be given RICE plus the MTD of lenalidomide. The starting dose of lenalidomide in Stage II will be modified for reduced renal function as outlined in Section 5.4.2.

In both stage I and stage II, subjects who have stable disease or progression of disease after 2 cycles of RICER will be taken off study. Subjects who achieve > PR to 2 cycles of RICER will receive a third cycle followed by stem cell collection and ASCT.

Each cycle is 14 days. Delays in initiating a new cycle are allowed up to 14 days for Stages I and II. The planned number of cycles is 3.

After the second cycle, restaging with PET and CT scans is performed. Patients with progressive disease are removed from the study, chemosensitive patients (CR/Cru and PR) proceed with third cycle of RICER. Stem cell collection will be completed within 10-14 days after third cycle of RICER. HDCMT-autoSCT will be performed after patient recovers from stem cell collection toxicities. HDCMT (high dose chemotherapy) followed by autologous stem cell transplant involves administration of chemotherapy with BEAM (BCNU, Etoposide, Ara-C, Melphalan) followed by infusion of autologous stem cells. Involved-field radiation to the sites of bulky disease will be allowed prior to HDCMT-SCT.

Stage III, after recovery from aSCT, but not to exceed 90 days all eligible subjects will receive lenalidomide maintenance therapy (po daily on Days 1-21 q28 days) for up to 1 year. Delays in initiating a new cycle up to 28 days are allowed in Stage III. Subjects will be followed for progression- free survival and overall survival for up to 2 years. The starting dose of lenalidomide maintenance treatment will be based on calculated creatinine clearance within 28 days prior to the start of lenalidomide maintenance

  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.

  1. Age 18 years at the time of signing the informed consent form.
  2. Able to adhere to the study visit schedule and other protocol requirements.
  3. Histologically confirmed diffuse large B cell lymphoma
  4. Relapsed or refractory after one prior therapeutic treatment for DLBCL. Refractory is defined as patients received adequate prior treatment and did not respond during treatment or progressed within 90 days of last treatment.
  5. Measurable disease with at least on bidimensional lymph node or tumor mass >1.5 cm in the longest diameter that can be followed for response as a target lesion as measured by PET or CT
  6. Histologically confirmed involvement of the bone marrow by DLBCL on the bone marrow biopsy without other measurable disease
  7. Eligible for autologous stem cell transplant
  8. All previous cancer therapy, including radiation, hormonal therapy and surgery, must have been discontinued at least two weeks prior to treatment in this study.
  9. ECOG performance status of 2 at study entry (see Appendix B).
  10. Laboratory test results within these ranges:

    • Absolute neutrophil count >1000 /mm³
    • Platelet count > 50,000/mm³
    • Calculated creatinine clearance of ≥ 60 mL/min by Cockroft-Gault formula (Appendix E) for patients enrolled into the phase I portion of the study (Stage I). Calculated creatinine clearance of ≥ 30 mL/min by Cockroft-Gault formula for patients enrolled into the phase II portion of the study (Stage II). See Section 5.4.2 for lenalidomide dose adjustment for calculated creatinine clearance > 30ml/min and < 60ml/min.
    • Total bilirubin < 1.5 x ULN.
    • AST (SGOT) and ALT (SGPT) < 3 x ULN.
  11. Disease free of prior malignancies for > 5

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