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

NCT00533923 | Completed Phase 2

• 1 other identifier: 2002P000219
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

AML; ALL; CLL; Myelodysplastic Syndrome; Non-Hodgkin's Lymphoma; Hodgkin's Lymphoma; Multiple Myeloma; Aplastic Anemia; Myeloproliferative Disorder

Keywords

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)

Outcome Measures

Primary Outcomes (1)

• 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.

  Within 100 days of transplant

Secondary Outcomes (1)

• 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.

  Within 100 days of transplant

Interventions

Cyclophosphamide; Fludarabine; Cyclosporin; CAMPATH-1H (Alemtuzumab); GM-CSF DRUG

intravenous

Also known as: Cytoxan;, Fludara;, Leukine;

Eligibility Criteria

• Age: Up to 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• /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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead
• Bayer: collaborator

Study Sites (1)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes; Lymphoma, Non-Hodgkin; Hodgkin Disease; Multiple Myeloma; Anemia, Aplastic; Myeloproliferative Disorders; Neoplasm Metastasis

Interventions

Cyclophosphamide; fludarabine; Cyclosporine; Alemtuzumab; Granulocyte-Macrophage Colony-Stimulating Factor; fludarabine phosphate; sargramostim

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Anemia; Bone Marrow Failure Disorders; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Biological Factors

Study Officials

• David F McDermott, MD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

• David E Avigan, MD

  Beth Israel Deaconess Medical Center

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 20, 2007
• First Posted: September 24, 2007
• Study Start: December 1, 2002
• Primary Completion: January 1, 2007
• Study Completion: January 1, 2007
• Last Updated: July 18, 2016

Record last verified: 2016-07

Locations

US (1)