Nonmyeloablative Allogeneic Stem Cell Transplantation From HLA-Matched Unrelated Donor for the Treatment of Hematologic Disorders

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2011 by Beth Israel Deaconess Medical Center.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Bayer
Information provided by:
Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier:
NCT00533923
First received: September 20, 2007
Last updated: June 22, 2011
Last verified: June 2011
  Purpose

Allogeneic stem cell transplantation may provide long-term remissions for some patients with hematological malignancies. However, allogeneic transplantation is associated with a significant risk of potentially life threatening complications due to the effects of chemotherapy and radiation on the body and the risks of serious infection. In addition, patients may develop a condition called Graft versus host disease that arises from an inflammatory reaction of the donor cells against the recipient's normal tissues. The risk of graft versus host disease is somewhat increased in patients who are receiving a transplant from an unrelated donor.

One approach to reduce the toxicity of allogeneic transplantation is a strategy call nonmyeloablative or "mini" transplants. In this approach, patients receive a lower dose of chemotherapy in an effort to limit treatment related side effects. Patients undergoing this kind of transplant remain at risk for graft versus host disease particularly if they receive a transplant from an unrelated donor. The purpose of this research study is to examine the ability of a drug called CAMPATH-1H to reduce the risk of graft versus host disease and make transplantation safer. CAMPATH-1H binds to and eliminates cells in the system such as T cells that can cause graft versus host disease (GvHD). As a result, earlier studies have shown that patients who receive CAMPATH-1H with an allogeneic transplant have a lower risk of GvHD. In the present study, we will examine the impact of treatment with CAMPATH-1H as part of an allogeneic transplant on the development of GvHD and infection. In addition, we will study the effects of CAMPATH-1H on the immune system by testing blood samples in the laboratory.


Condition Intervention Phase
AML
ALL
CLL
Myelodysplastic Syndrome
Non-Hodgkin's Lymphoma
Hodgkin's Lymphoma
Multiple Myeloma
Aplastic Anemia
Myeloproliferative Disorder
Drug: Cyclophosphamide; Fludarabine; Cyclosporin; CAMPATH-1H (Alemtuzumab); GM-CSF
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Nonmyeloablative Allogeneic Stem Cell Transplantation From HLA-Matched Unrelated Donor for the Treatment of Hematologic Disorders

Resource links provided by NLM:


Further study details as provided by Beth Israel Deaconess Medical Center:

Primary Outcome Measures:
  • Primary objective of study is to determine the safety of non-myeloablative allogenic stem cell transplantation from matched unrelated donors in patients with hematologic malignancies with a focus on the incidence of treatment-related mortality. [ Time Frame: Within 100 days of transplant ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Secondary clinical endpoints includes; incidence of graft failure or rejection; incidence and severity of acute and chronic GVHD; tumor response, and long-term overall and disease-free survival. [ Time Frame: Within 100 days of transplant ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 25
Study Start Date: December 2002
Primary Completion Date: January 2007 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Cyclophosphamide; Fludarabine; Cyclosporin; CAMPATH-1H (Alemtuzumab); GM-CSF
    intravenous
    Other Names:
    • Cytoxan;
    • Fludara;
    • Leukine;
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age less than 65 years. There is no lower age limit. Patients 65 years and older will be accrued on a case-by-case basis to this protocol, after discussion and approval by the principal investigator. The acceptance to this protocol for such patients would be based on the absence of coexisting medical problems, which would seriously compromise the patient's ability to tolerate the known morbidity and risks of bone marrow transplantation.
  • Patients must have a 5/6 or 6/6 HLA matched, unrelated donor of bone marrow stem cells.
  • Each patient must be willing to participate as a research subject and must sign an informed consent form after having been advised as to the nature and risk of the study prior to entering the protocol. Parents or legal guardians of patients who are minors will sign the informed consent form after being advised of the nature and risks of the study. Attending physicians in the Bone Marrow Transplant Service will enroll patients to this study and will obtain written consents.

Eligibility Criteria - Donor

  • 5/6 or 6/6 HLA matched with the recipient as determined by molecular testing. Donors will be identified through the National Marrow Donor Program for unrelated donors.
  • Donor selection will be performed as outlined in the donor selection SOP's. In patients who have more than one potential donor preference will be given to donors who have no evidence of CMV exposure (if the recipient is CMV-), those who are younger and those who are male. Selection of an unrelated donor from the NMDP registry will proceed according to the donor selection SOP. Molecular testing of HLA-A, B, and DR alleles will identify potential donors and the American Red Cross HLA lab will confirm all typing. Donor selection will be coordinated with transplant physician and the HLA laboratory director. Preference will be given to donors who are 6/6 molecular matches, those who are CMV- (if the recipient is CMV-), those who are younger, and males.

Exclusion Criteria:

  • Active CNS leukemia involvement.
  • Female patients who are pregnant or breast feeding
  • Karnofsky performance status < 70%, (appendix 1).
  • Left ventricular ejection fraction of < 40%.
  • Serum creatinine > 1.5 X normal
  • Patients seropositive for HIV; HTLV -1, or with evidence of chronic active hepatitis as demonstrated by detection of hepatitis surface antigen in the serum
  • Patients with serologic evidence of hepatitis B or C exposure will undergo liver biopsy to assess for presence of active hepatitis or fibrosis and quantification of risk of proceeding with transplant
  • Patients not providing informed consent.
  • Patients with known hypersensitivity to E. Coli derived products.
  • SGOT and SGPT > 2.5 x ULN, unless thought to be disease related
  • Total bilirubin > 2.0 mg/dl, with direct bilirubin > 0.5 mg/dl
  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: NCT00533923

Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
Bayer
Investigators
Principal Investigator: David F McDermott, MD Beth Israel Deaconess Medical Center
Study Director: David E Avigan, MD Beth Israel Deaconess Medical Center
  More Information

No publications provided

Responsible Party: David McDermott, MD, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT00533923     History of Changes
Other Study ID Numbers: 2002P000219
Study First Received: September 20, 2007
Last Updated: June 22, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Beth Israel Deaconess Medical Center:
Nonmyeloablative Allogeneic Stem Cell Transplantation
mini-transplant
AML
ALL
CML
CLL
Myelodysplastic syndrome
Relapsed non-Hodgkin's or Hodgkin's lymphoma
Relapsed multiple myeloma
Aplastic anemia
Myeloproliferative disorder
GM-CSF
Cyclosporin
Fludarabine (FLUDARA)
Cyclophosphamide
CAMPATH-1H
GVHD
CMV
AML in first remission, first relapse or subsequent remission
ALL in first relapse, second or subsequent remission
ALL in first remission, in a high-risk category
Aplastic anemia characterized by ANC< 1000 and/or platelets < 30 without transfusional support
Myeloproliferative disorder (P Vera, CMML, ET)

Additional relevant MeSH terms:
Anemia
Anemia, Aplastic
Hematologic Diseases
Hodgkin Disease
Lymphoma
Lymphoma, Non-Hodgkin
Multiple Myeloma
Neoplasms, Plasma Cell
Myelodysplastic Syndromes
Preleukemia
Myeloproliferative Disorders
Bone Marrow Diseases
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hemorrhagic Disorders
Precancerous Conditions
Cyclophosphamide
Cyclosporins
Cyclosporine
Fludarabine phosphate
Fludarabine

ClinicalTrials.gov processed this record on August 20, 2014