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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2009 by National Cancer Institute (NCI).
Recruitment status was  Not yet recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00908180
First received: May 22, 2009
Last updated: August 1, 2013
Last verified: June 2009
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Reduced Intensity Allogeneic Transplantation for Refractory Hodgkin Lymphoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free survival at 3 years [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Donor engraftment rates, including chimerism at 3 and 6 months [ Designated as safety issue: No ]
  • Non-relapse mortality at 100 days, 1 year, and 2 years post-transplant [ Designated as safety issue: No ]
  • Incidence of grade II-IV toxicity as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
  • Incidence, severity, and timing of acute and chronic graft-versus-host disease [ Designated as safety issue: No ]
  • Response rates [ Designated as safety issue: No ]
  • Relapse rates [ Designated as safety issue: No ]
  • Response to donor lymphocyte infusions [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]

Estimated Enrollment: 47
Study Start Date: July 2009
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   16 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00908180

Sponsors and Collaborators
Cancer Research UK
Investigators
Principal Investigator: Karl Peggs, MD University College London (UCL) Cancer Institute
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00908180     History of Changes
Other Study ID Numbers: CRUK-PAIReD, CDR0000640493, EUDRACT-2008-004956-60, EU-20930, UCL/08/0121
Study First Received: May 22, 2009
Last Updated: August 1, 2013
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
recurrent adult Hodgkin lymphoma

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Carmustine
Melphalan
Etoposide phosphate
Alemtuzumab
Cytarabine
Etoposide
Cyclosporins
Cyclosporine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 01, 2014