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

NCT ID: NCT00908180

Last Updated: 2013-08-02

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 47 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-07-31

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.

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.

Conditions

Lymphoma

Keywords

recurrent adult Hodgkin lymphoma

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

alemtuzumab

Intervention Type: BIOLOGICAL

donor lymphocytes

Intervention Type: BIOLOGICAL

carmustine

Intervention Type: DRUG

cyclosporine

Intervention Type: DRUG

cytarabine

Intervention Type: DRUG

etoposide

Intervention Type: DRUG

melphalan

Intervention Type: DRUG

allogeneic hematopoietic stem cell transplantation

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cancer Research UK

OTHER

Sponsor Role: lead

Principal Investigators

Karl Peggs, MD

Role: PRINCIPAL_INVESTIGATOR

University College London (UCL) Cancer Institute

References

Das-Gupta E, Thomson KJ, Bloor AJC, Clark AD, Mackinnon S, Kayani I, Clifton-Hadley L, Patrick P, El-Mehidi N, Lawrie A, Kirkwood AA, Russell NH, Linch DC, Peggs KS. Allo-HSCT in transplant-naive patients with Hodgkin lymphoma: a single-arm, multicenter study. Blood Adv. 2019 Dec 23;3(24):4264-4270. doi: 10.1182/bloodadvances.2019001016.

Reference Type: DERIVED

PMID: 31869413 (View on PubMed)

Other Identifiers

CDR0000640493

Identifier Type: REGISTRY

Identifier Source: secondary_id

EUDRACT-2008-004956-60

Identifier Type: -

Identifier Source: secondary_id

EU-20930

Identifier Type: -

Identifier Source: secondary_id

UCL/08/0121

Identifier Type: -

Identifier Source: secondary_id

CRUK-PAIReD

Identifier Type: -

Identifier Source: org_study_id