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