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

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT00908180
• Other study ID #: CRUK-PAIReD
• Secondary ID: CDR0000640493EUD
• Status: Not yet recruiting
• Phase: Phase 2
• First received: May 22, 2009
• Last updated: August 1, 2013
• Start date: July 2009

Study information

• Verified date: June 2009
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 47
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years to 65 Years

Eligibility

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

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior high-dose therapy or allograft

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hodgkin Disease
• Lymphoma

Intervention

Biological:
• alemtuzumab

• donor lymphocytes

Drug:
• carmustine

• cyclosporine

• cytarabine

• etoposide

• melphalan

Procedure:
• allogeneic hematopoietic stem cell transplantation

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Cancer Research UK

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival at 3 years			No
Secondary	Donor engraftment rates, including chimerism at 3 and 6 months			No
Secondary	Non-relapse mortality at 100 days, 1 year, and 2 years post-transplant			No
Secondary	Incidence of grade II-IV toxicity as assessed by NCI CTCAE v3.0			Yes
Secondary	Incidence, severity, and timing of acute and chronic graft-versus-host disease			No
Secondary	Response rates			No
Secondary	Relapse rates			No
Secondary	Response to donor lymphocyte infusions			No
Secondary	Overall survival			No