Peripheral Stem Cell Transplant Plus Monoclonal Antibody Therapy in Treating Patients With High-Risk Hematologic Cancer, Refractory Breast or Kidney Cancer, or Melanoma - Full Text View

Sponsor:	Duke University
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00004143

Purpose

RATIONALE: Giving low doses of chemotherapy, such as fludarabine and cyclophosphamide, before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving a monoclonal antibody, alemtuzumab, at the time of transplant may stop this from happening.

PURPOSE: This phase II trial is studying peripheral stem cell transplant and monoclonal antibody therapy to see how well they work in treating patients with high-risk hematologic cancer, refractory breast or kidney cancer, or melanoma.

Condition	Intervention	Phase
Breast Cancer Chronic Myeloproliferative Disorders Kidney Cancer Leukemia Melanoma (Skin) Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases	Biological: alemtuzumab Biological: filgrastim Drug: cyclophosphamide Drug: fludarabine phosphate Procedure: in vitro-treated peripheral blood stem cell transplantation Procedure: peripheral blood stem cell transplantation	Phase II

Study Type:	Interventional
Study Design:	Treatment
Official Title:	Allogeneic Mixed Chimerism Stem Cell Transplantation Utilizing In Vivo and In Vitro CAMPATH-1H for High Risk Diseases

Resource links provided by NLM:

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

Primary Outcome Measures:

Clinical disease-free survival (DFS) [ Designated as safety issue: No ]

Secondary Outcome Measures:

Molecular complete response (CR) in patients with clinical CR/unconfirmed CR [ Designated as safety issue: No ]
Molecular DFS [ Designated as safety issue: No ]
Immunologic response against autologous tumor [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]

Estimated Enrollment:	70
Study Start Date:	September 1999

Detailed Description:

OBJECTIVES:

Determine the efficacy, in terms of mortality, occurrence of acute graft versus-host-disease, and grade 3/4 toxicity, of in vivo and in vitro alemtuzumab (monoclonal antibody CD52; Campath-1H) administered concurrently with nonmyeloablative fludarabine and cyclophosphamide, followed by HLA identical matched sibling allogeneic peripheral blood stem cell transplantation in patients with hematologic malignancies or refractory breast or renal cell cancer or melanoma.
Determine the engraftment rate, response rate, and long term survival of patients receiving this regimen.
Determine the recovery of immune function post engraftment in patients treated with this regimen.
Determine the pharmacokinetics of cyclophosphamide administered in this regimen.
Assess graft-versus-tumor effects in patients treated with this regimen.

OUTLINE: Patients receive alemtuzumab (monoclonal antibody CD52; Campath-1H) IV over 3 hours on days -6 to -2 and fludarabine IV over 30 minutes and cyclophosphamide IV over 1 hour on days -5 to -2. Allogeneic peripheral blood stem cells and alemtuzumab are infused on days 0 and 1. Filgrastim (G-CSF) is administered subcutaneously beginning on day 1 and continuing until blood counts recover.

Patients are followed daily until day 60, twice a week until day 100, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 70 patients will be accrued for this study within 3 years.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of any one of the following:
- Relapsed or refractory hematologic malignancy
  - Acute myeloid leukemia
  - Chronic myeloid leukemia
  - Acute lymphocytic leukemia
  - Chronic lymphocytic leukemia
  - Multiple myeloma
  - Myeloproliferative or myelodysplastic disorders
  - Not eligible for full myeloablative matched sibling transplant
- Bone marrow failure
  - Severe or very severe aplastic anemia
  - Myelofibrosis or paroxysmal nocturnal hemoglobinuria
    - Increased blast cells (at least 5%) in peripheral blood or bone marrow OR
    - Visceral organ damage due to disease
      - Severe fibrosis of bone marrow
      - Severe Budd-Chiari
      - Mild hepatic/portal clot by ultrasound or hepatic biopsy
  - Drug induced marrow aplasia
- Hemoglobinopathies
  - Severe sickle cell anemia
  - Thalassemia with cardiac or hepatic damage
- Solid tumor with metastatic disease and failed at least 1 standard regimen
  - Breast cancer
    - Progressed after doxorubicin and cyclophosphamide
  - Renal cell cancer
    - Failed interleukin-2 therapy
  - Melanoma
    - Failed interleukin-2 therapy
Must have 6/6 HLA matched sibling donor
Hormone receptor status:
- Not specified

PATIENT CHARACTERISTICS:

Age:

18 and over

Sex:

Not specified

Menopausal status:

Not specified

Performance status:

CALGB 0-2

Life expectancy:

At least 6 weeks

Hematopoietic:

Not specified

Hepatic:

Not specified

Renal:

Not specified

Cardiovascular:

Ejection fraction greater than 40%

Pulmonary:

DLCO greater than 40%

Other:

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No other major medical or psychiatric illness that would preclude compliance
No allergy to murine protein
HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy:

See Disease Characteristics

Chemotherapy:

See Disease Characteristics
Recovered from prior chemotherapy

Endocrine therapy:

Not specified

Radiotherapy:

Recovered from prior radiotherapy

Surgery:

Not specified

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00004143

Locations

United States, Florida
Florida Hospital Cancer Institute
Orlando, Florida, United States, 32804
United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710

Sponsors and Collaborators

Duke University

National Cancer Institute (NCI)

Investigators

Study Chair:

David A. Rizzieri, MD

Duke University

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000067374, DUMC-1340-99-7, NCI-G99-1617
Study First Received:	December 10, 1999
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00004143 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

stage IV breast cancer
recurrent breast cancer
refractory multiple myeloma
stage IV renal cell cancer
recurrent renal cell cancer
recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
relapsing chronic myelogenous leukemia
refractory chronic lymphocytic leukemia
stage IV melanoma
recurrent melanoma
polycythemia vera
chronic idiopathic myelofibrosis

essential thrombocythemia
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
chronic eosinophilic leukemia
chronic neutrophilic leukemia
atypical chronic myeloid leukemia
myelodysplastic/myeloproliferative disease, unclassifiable
adult acute myeloid leukemia with t(8;21)(q22;q22)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with t(15;17)(q22;q12)

Additional relevant MeSH terms:

Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Urogenital Neoplasms
Urologic Neoplasms
Preleukemia
Neoplasms by Site
Hemorrhagic Disorders
Pathologic Processes
Therapeutic Uses
Alemtuzumab
Cardiovascular Diseases
Kidney Diseases
Breast Diseases

Immunoproliferative Disorders
Immune System Diseases
Hematologic Diseases
Myeloproliferative Disorders
Breast Neoplasms
Carcinoma
Multiple Myeloma
Neuroectodermal Tumors
Neoplasms
Fludarabine
Neoplasms, Glandular and Epithelial
Antimetabolites
Vidarabine
Immunologic Factors
Precancerous Conditions

ClinicalTrials.gov processed this record on November 27, 2009