Fludarabine Phosphate, Melphalan, and Alemtuzumab Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed Hodgkin Lymphoma

This study is not yet open for participant recruitment.
Verified June 2009 by National Cancer Institute (NCI)
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00907036
First received: May 21, 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 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.


Condition Intervention Phase
Lymphoma
Biological: alemtuzumab
Biological: donor lymphocytes
Drug: cyclosporine
Drug: fludarabine phosphate
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 Sibling Allogeneic Transplantation for Relapsed, Chemosensitive, PET-positive Hodgkin Lymphoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 3-year progression-free survival [ 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 and at 1 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 graft-vs-host disease [ Designated as safety issue: Yes ]
  • 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: 49
Study Start Date: July 2009
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
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.

  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 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00907036

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: NCT00907036     History of Changes
Other Study ID Numbers: CRUK-ReACH, CDR0000640500, EUDRACT-2008-004956-60, EU-20928, UCL/08/0122
Study First Received: May 21, 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
Cyclosporins
Cyclosporine
Melphalan
Fludarabine monophosphate
Campath 1G
Vidarabine
Fludarabine
Alemtuzumab
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents
Myeloablative Agonists
Antineoplastic Agents
Antineoplastic Agents, Alkylating

ClinicalTrials.gov processed this record on April 23, 2014