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Fludarabine Phosphate, Melphalan, and Alemtuzumab Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed Hodgkin Lymphoma

Primary Purpose

Lymphoma

Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
alemtuzumab
donor lymphocytes
cyclosporine
fludarabine phosphate
melphalan
allogeneic hematopoietic stem cell transplantation
Sponsored by
Cancer Research UK
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring recurrent adult Hodgkin lymphoma

Eligibility Criteria

16 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS:

  • Confirmed diagnosis of Hodgkin lymphoma, meeting all of the following criteria:

    • Achieved partial or complete remission (using standard criteria) after salvage chemotherapy
    • Relapsed after first remission with residual fludeoxyglucose F 18-avid lesions
  • Available HLA-matched sibling donor

PATIENT CHARACTERISTICS:

  • WHO performance status 0-1
  • Creatinine clearance ≥ 50 mL/min (measured by EDTA clearance or 24-hour urine collection)
  • Serum bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • Alkaline phosphatase ≤ 2 times ULN
  • LVEF ≥ 40%
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 2 months (or 3 months for women) after completion of study therapy
  • No other malignancy within the past 5 years except for nonmelanoma skin tumors or stage 0 (in situ) cervical carcinoma
  • No HIV positivity
  • No symptomatic respiratory compromise
  • No concurrent serious medical condition that would preclude transplantation

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior high-dose therapy or allograft

Sites / Locations

    Outcomes

    Primary Outcome Measures

    3-year progression-free survival

    Secondary Outcome Measures

    Donor engraftment rates, including chimerism at 3 and 6 months
    Non-relapse mortality at 100 days and at 1 and 2 years post-transplant
    Incidence of grade II-IV toxicity as assessed by NCI CTCAE v3.0
    Incidence, severity, and timing of graft-vs-host disease
    Response rates
    Relapse rates
    Response to donor lymphocyte infusions
    Overall survival

    Full Information

    First Posted
    May 21, 2009
    Last Updated
    August 1, 2013
    Sponsor
    Cancer Research UK
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00907036
    Brief Title
    Fludarabine Phosphate, Melphalan, and Alemtuzumab Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed Hodgkin Lymphoma
    Official Title
    A Phase II Study of Reduced Intensity Sibling Allogeneic Transplantation for Relapsed, Chemosensitive, PET-positive Hodgkin Lymphoma
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2009
    Overall Recruitment Status
    Unknown status
    Study Start Date
    July 2009 (undefined)
    Primary Completion Date
    July 2015 (Anticipated)
    Study Completion Date
    undefined (undefined)

    3. Sponsor/Collaborators

    Name of the Sponsor
    Cancer Research UK

    4. Oversight

    5. Study Description

    Brief Summary
    RATIONALE: Giving chemotherapy before a donor stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. Also, monoclonal antibodies, such as alemtuzumab, can find cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine before and after the transplant may stop this from happening. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer cells as not belonging in the patient's body and destroy them (called graft-versus-tumor effect). Giving an infusion of the donor's white blood cells (donor lymphocyte infusion) may boost this effect. PURPOSE: This phase II trial is studying the side effects of fludarabine phosphate, melphalan, and alemtuzumab followed by donor stem cell transplant in treating patients with relapsed Hodgkin lymphoma.
    Detailed Description
    OBJECTIVES: To document the toxicity, feasibility, and survival after reduced-intensity conditioning followed by allogeneic hematopoietic stem cell transplantation from a matched sibling donor in patients with relapsed, chemosensitive Hodgkin lymphoma. OUTLINE: This is a multicenter study. Reduced-intensity conditioning: Patients receive fludarabine phosphate IV on days -7 to -3, melphalan IV over 30 minutes on day -2, and alemtuzumab IV on day -1. Transplantation: Patients undergo donor stem cell infusion on day 0. Graft-vs-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV or orally on days -1 to 60, followed by a taper until 3 months post-transplantation, in the absence of GVHD. Donor-lymphocyte infusion (DLI): DLI is used for the eradication of mixed chimerism and for the management of residual or relapsed disease. If necessary, patients undergo DLI every 3 months until the desired endpoint is achieved or GVHD develops. After completion of study therapy, patients are followed up every 3 months for 3 years. This study is peer reviewed and funded or endorsed by Cancer Research UK.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Lymphoma
    Keywords
    recurrent adult Hodgkin lymphoma

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Masking
    None (Open Label)
    Enrollment
    49 (Anticipated)

    8. Arms, Groups, and Interventions

    Intervention Type
    Biological
    Intervention Name(s)
    alemtuzumab
    Intervention Type
    Biological
    Intervention Name(s)
    donor lymphocytes
    Intervention Type
    Drug
    Intervention Name(s)
    cyclosporine
    Intervention Type
    Drug
    Intervention Name(s)
    fludarabine phosphate
    Intervention Type
    Drug
    Intervention Name(s)
    melphalan
    Intervention Type
    Procedure
    Intervention Name(s)
    allogeneic hematopoietic stem cell transplantation
    Primary Outcome Measure Information:
    Title
    3-year progression-free survival
    Secondary Outcome Measure Information:
    Title
    Donor engraftment rates, including chimerism at 3 and 6 months
    Title
    Non-relapse mortality at 100 days and at 1 and 2 years post-transplant
    Title
    Incidence of grade II-IV toxicity as assessed by NCI CTCAE v3.0
    Title
    Incidence, severity, and timing of graft-vs-host disease
    Title
    Response rates
    Title
    Relapse rates
    Title
    Response to donor lymphocyte infusions
    Title
    Overall survival

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    16 Years
    Maximum Age & Unit of Time
    65 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    DISEASE CHARACTERISTICS: Confirmed diagnosis of Hodgkin lymphoma, meeting all of the following criteria: Achieved partial or complete remission (using standard criteria) after salvage chemotherapy Relapsed after first remission with residual fludeoxyglucose F 18-avid lesions Available HLA-matched sibling donor PATIENT CHARACTERISTICS: WHO performance status 0-1 Creatinine clearance ≥ 50 mL/min (measured by EDTA clearance or 24-hour urine collection) Serum bilirubin ≤ 1.5 times upper limit of normal (ULN) Alkaline phosphatase ≤ 2 times ULN LVEF ≥ 40% Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 2 months (or 3 months for women) after completion of study therapy No other malignancy within the past 5 years except for nonmelanoma skin tumors or stage 0 (in situ) cervical carcinoma No HIV positivity No symptomatic respiratory compromise No concurrent serious medical condition that would preclude transplantation PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior high-dose therapy or allograft
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Karl Peggs, MD
    Organizational Affiliation
    University College London (UCL) Cancer Institute
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

    Fludarabine Phosphate, Melphalan, and Alemtuzumab Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed Hodgkin Lymphoma

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