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Removal of T Cells to Prevent Graft-Versus-Host Disease in Patients Undergoing Bone Marrow Transplantation
This study is ongoing, but not recruiting participants.
First Received: May 2, 2000   Last Updated: February 6, 2009   History of Changes
Sponsors and Collaborators: H. Lee Moffitt Cancer Center and Research Institute
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00005641
  Purpose

RATIONALE: Bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy used to kill tumor cells. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Eliminating the T cells from the donor cells before transplanting them may prevent this from happening.

PURPOSE: Phase II trial to study the effectiveness of T cell removal to prevent graft-versus-host disease in patients who are undergoing bone marrow transplantation from a donor.


Condition Intervention Phase
Chronic Myeloproliferative Disorders
Graft Versus Host Disease
Leukemia
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Biological: anti-thymocyte globulin
Drug: busulfan
Drug: cyclophosphamide
Drug: cyclosporine
Drug: leucovorin calcium
Drug: methotrexate
Drug: methylprednisolone
Procedure: allogeneic bone marrow transplantation
Procedure: in vitro-treated bone marrow transplantation
Radiation: radiation therapy
Phase II

Genetics Home Reference related topics: aceruloplasminemia hemophilia
MedlinePlus related topics: Anemia Bone Marrow Transplantation Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood Multiple Myeloma Radiation Therapy
Drug Information available for: Cyclophosphamide Busulfan Leucovorin Methotrexate Citrovorum factor Cyclosporine Cyclosporin Methylprednisolone Leucovorin Calcium Folinic acid calcium salt pentahydrate
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment
Official Title: T-Cell Depletion for Graft-Versus-Host Disease (GVHD) Prevention in High Risk Matched and Mismatched Allogeneic Bone Marrow Transplantation

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

Study Start Date: July 2000
Detailed Description:

OBJECTIVES: I. Determine the incidence and severity of graft vs host disease (GVHD) following allogeneic bone marrow transplantation with marrow grafts modified by T cell depletion with counterflow centrifugal elutriation and CD34+ cell selection in patients at high risk for GVHD. II. Determine the incidence of graft failure following this treatment regimen in this patient population. III. Determine the relapse rate and overall survival in this patient population treated with this regimen.

OUTLINE: Patients with unrelated donors, mismatched related donors, or matched related donors diagnosed with acute lymphocytic leukemia, chronic lymphocytic leukemia, myeloma, or advanced acute myeloid leukemia (AML), receive cyclophosphamide IV over 60 minutes on days -6 and -5 and fractionated total body irradiation (TBI) 3 times a day on days -3 through -1, and twice on day 0. Patients receive graft vs host disease (GVHD) prophylaxis with anti-thymocyte globulin (ATG) IV over 8 hours on days -2 and -1. Patients undergo allogeneic bone marrow transplantation (ABMT) on day 0 with marrow grafts modified by T cell depletion with counterflow centrifugal elutriation and CD34+ selection. Patients unable to receive TBI due to matched or mismatched related donors, or age (56 to 60), or patients diagnosed with AML-CR1, chronic myelogenous leukemia, myelodysplastic syndrome, or myeloproliferative disorders with matched related donors, receive oral busulfan every 6 hours on days -7 through -4, cyclophosphamide IV over 60 minutes on days -3 and -2, and ATG IV over 8 hours on days -2 and -1 for GVHD prophylaxis. Patients undergo T cell depleted ABMT on day 0. At pretransplantation, patients with acute leukemia receive intrathecal (IT) methotrexate (MTX) following lumbar puncture. At 48 hours following IT MTX, patients with CNS involvement receive a second dose of IT MTX followed by oral leucovorin calcium every 6 hours for 4 doses. Patients with prior CNS involvement receive cranial radiotherapy for 2 weeks. Following AMBT, patients undergo GVHD prophylaxis consisting of methylprednisolone IV every 12 hours on days 5-22, and then once daily on days 23-28 and cyclosporine IV or orally twice daily beginning on day -1 and continuing until 7-9 months following ABMT. Patients are followed every 3 months until death.

PROJECTED ACCRUAL: Approximately 40 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   15 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS: Histologically confirmed malignancy Acute myeloid leukemia (AML) Complete remission 1 (CR1): high risk defined by poor cytogenetics (e.g., deletions, additions, or multiple abnormalities) Complete remission 2 (CR2) Induction failures Relapse: at least one reinduction attempt if at least 10% marrow blasts Acute lymphocytic leukemia CR1: high risk defined by overt CNS involvement or poor cytogenetics (e.g., additions, deletions, translocations, or multiple abnormalities) CR2 Induction failures Relapse as for AML Chronic myelogenous leukemia Chronic phase (CP) 1 Accelerated phase (AP)/CP2: blast phase patients require induction and achievement of a second chronic phase prior to transplantation Chronic lymphocytic leukemia Relapse: any stage and must have received no greater than 3 regimens since diagnosis Multiple myeloma Primary refractory disease at diagnosis Relapse (no greater than 2): sensitive disease Plasma cell leukemia Inability to achieve a complete remission or relapse after autologous transplantation (no greater than 40 years) Myelodysplasia All FAB subtypes Myeloproliferative disorders Poor response to medical therapy OR Cytogenetic abnormalities Severe aplastic anemia (SAA) (for unrelated and/or mismatched donors) Very SAA at diagnosis OR SAA: induction failures One antigen mismatch (recipient age 15 to 55) Related donors may be A, B, or DR mismatched Unrelated donors may be A or B mismatched (DRB1 match) Phenotypic (6 out of 6) match Recipient age 51 to 60 if related donor Recipient age 41 to 55 if unrelated donor

PATIENT CHARACTERISTICS: Age: 15 to 60 Performance status: ECOG 0-1 Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Bilirubin no greater than 2.0 mg/dL SGOT/SGPT no greater than 3 times normal PT/PTT normal Renal: Creatinine no greater than 2.0 mg/dL Creatinine clearance at least 60 mL/min Cardiovascular: LVEF at least 45% by MUGA scan or echocardiography Greater than 6 months since myocardial infarction No uncontrolled arrhythmias Pulmonary: FEV1 and DCLO at least 50% predicted Other: No psychosocial conditions that would preclude study No uncontrolled diabetes mellitus No uncontrolled thyroid disease No active serious infections HIV negative Not pregnant or nursing Negative pregnancy test

PRIOR CONCURRENT THERAPY: See Disease Characteristics

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00005641

Locations
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Investigators
Study Chair: Steven C. Goldstein, MD H. Lee Moffitt Cancer Center and Research Institute
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000067804, MCC-11587, MCC-IRB-4599, NCI-G00-1781
Study First Received: May 2, 2000
Last Updated: February 6, 2009
ClinicalTrials.gov Identifier: NCT00005641     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
recurrent childhood acute lymphoblastic leukemia
refractory multiple myeloma
stage 0 chronic lymphocytic leukemia
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
stage I chronic lymphocytic leukemia
stage II chronic lymphocytic leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
recurrent childhood acute myeloid leukemia
recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
relapsing chronic myelogenous leukemia
refractory chronic lymphocytic leukemia
chronic phase chronic myelogenous leukemia
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
adult acute myeloid leukemia in remission
adult acute lymphoblastic leukemia in remission
polycythemia vera
chronic idiopathic myelofibrosis
essential thrombocythemia
refractory anemia
refractory anemia with ringed sideroblasts
refractory anemia with excess blasts
refractory anemia with excess blasts in transformation
chronic myelomonocytic leukemia
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes

Study placed in the following topic categories:
Anti-Inflammatory Agents
Polycythemia
Chronic Myelomonocytic Leukemia
Blast Crisis
Cyclosporine
Methylprednisolone
Hormone Antagonists
Miconazole
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Hormones
Cyclosporins
Refractory Anemia
Graft Versus Host Disease
Preleukemia
Acute Myelocytic Leukemia
Anemia, Refractory
Hemorrhagic Disorders
Acute Myeloid Leukemia, Adult
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasm Metastasis
Methotrexate
Thrombocythemia, Hemorrhagic
Methylprednisolone Hemisuccinate
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunoproliferative Disorders
Antineoplastic Agents, Hormonal
Hematologic Diseases
Leukemia, Myelomonocytic, Chronic
Blood Coagulation Disorders

Additional relevant MeSH terms:
Anti-Inflammatory Agents
Anti-Infective Agents
Antimetabolites, Antineoplastic
Cyclosporine
Molecular Mechanisms of Pharmacological Action
Methylprednisolone
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Hormones
Cyclosporins
Preleukemia
Pathologic Processes
Hemorrhagic Disorders
Therapeutic Uses
Abortifacient Agents
Methotrexate
Cardiovascular Diseases
Dermatologic Agents
Nucleic Acid Synthesis Inhibitors
Methylprednisolone Hemisuccinate
Immunoproliferative Disorders
Antineoplastic Agents, Hormonal
Immune System Diseases
Hematologic Diseases
Myeloproliferative Disorders
Abortifacient Agents, Nonsteroidal
Glucocorticoids
Multiple Myeloma
Neoplasms

ClinicalTrials.gov processed this record on May 07, 2009