Carmustine, Etoposide, Cytarabine, Melphalan, and Alemtuzumab Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma

Sponsor

Cancer Research UK (Other)

Overall Status

Unknown status

CT.gov ID

NCT00908180

Collaborator

(none)

Enrollment

Study Details

Study Description

Brief Summary

RATIONALE: Giving chemotherapy before a donor stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. 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 giving carmustine together with etoposide, cytarabine, melphalan, and alemtuzumab followed by donor stem cell transplant and to see how well it works in treating patients with relapsed or refractory Hodgkin lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: alemtuzumab Biological: donor lymphocytes Drug: carmustine Drug: cyclosporine Drug: cytarabine Drug: etoposide Drug: melphalan Procedure: allogeneic hematopoietic stem cell transplantation	Phase 2

Detailed Description

OBJECTIVES:

To document the toxicity and feasibility of reduced-intensity conditioning regimen comprising carmustine, etoposide, cytarabine, melphalan, and alemtuzumab followed by allogeneic hematopoietic stem cell transplantation in patients with primary refractory or relapsed Hodgkin lymphoma.
To document the survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

Conditioning regimen: Patients receive BEAM chemotherapy comprising carmustine IV over 2 hours on day -6, etoposide IV over ≥ 1 hour on days -5 to -2, cytarabine IV over 15 minutes twice daily on days -5 to -2, and melphalan IV on day -1. Patients also receive alemtuzumab IV on days -5 to -1.
Allogeneic hematopoietic stem cell transplantation (HSCT): Patients undergo allogeneic HSCT on day 0.
Graft-versus-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV (or orally once tolerable) beginning on day -1 and continuing until day 60, followed by a taper in the absence of GVHD.
Donor lymphocyte infusion (DLI): Patients with mixed chimerism or stable residual disease at 6 months after HSCT or disease progression or relapse at any time after HSCT may receive DLI in the absence of GVHD.

After completion of study treatment, patients are followed periodically for 3 years.

Peer Reviewed and Funded or Endorsed by Cancer Research UK.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

47 participants

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Study of Reduced Intensity Allogeneic Transplantation for Refractory Hodgkin Lymphoma

Study Start Date :

Jul 1, 2009

Anticipated Primary Completion Date :

Jul 1, 2014

Outcome Measures

Primary Outcome Measures

Progression-free survival at 3 years []

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Confirmed diagnosis of Hodgkin lymphoma, meeting 1 of the following criteria:
Refractory to initial multi-agent induction therapy and achieved less than a complete response to one line of salvage chemotherapy
In first relapse and achieved less than a partial response to one line of salvage chemotherapy
No progressive disease
Must have an HLA-matched (≥ 9/10) sibling or unrelated donor available

PATIENT CHARACTERISTICS:

WHO performance status 0-1
Creatinine clearance ≥ 50 mL/min
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 2-3 months after completion of study treatment
No HIV positivity
No other malignancy within the past 5 years, except for nonmelanoma skin cancer or stage 0 (in situ) cervical carcinoma
No concurrent serious medical condition that would preclude an allograft
No symptomatic respiratory compromise