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Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Cancer or Other Disease
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), November 2008
Sponsored by: National Heart, Lung, and Blood Institute (NHLBI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00398346
  Purpose

RATIONALE: Giving chemotherapy, such as fludarabine and cyclophosphamide, and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem 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. Removing T cells from the donor cells before transplant and giving cyclosporine or tacrolimus before and after transplant may stop this from happening. Giving an infusion of the donor's T cells (donor lymphocyte infusion) later may help the patient's immune system see any remaining cancer or abnormal cells as not belonging to the patient's body and destroy them (graft-versus-tumor effect).

PURPOSE: This phase II trial is studying how well a donor peripheral blood stem cell transplant works in treating patients with hematologic cancer or other disease.


Condition Intervention Phase
Cancer-Related Problem/Condition
Chronic Myeloproliferative Disorders
Graft Versus Host Disease
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Diseases
Small Intestine Cancer
Drug: cyclophosphamide
Drug: cyclosporine
Drug: fludarabine phosphate
Drug: tacrolimus
Drug: therapeutic allogeneic lymphocytes
Procedure: allogeneic hematopoietic stem cell transplantation
Procedure: in vitro-treated peripheral blood stem cell transplantation
Procedure: peripheral blood stem cell transplantation
Procedure: total-body irradiation
Phase II

Genetics Home Reference related topics: aceruloplasminemia hemophilia
MedlinePlus related topics: Anemia Cancer Intestinal Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood Lymphoma Multiple Myeloma
Drug Information available for: Cyclophosphamide Fludarabine Fludarabine monophosphate Tacrolimus Cyclosporin Cyclosporine Tacrolimus anhydrous
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: Peripheral Blood Stem Cell Allotransplantation for Hematological Malignancies Using a Positive Stem Cell Selection Technique for T-Cell Depletion, Followed by Delayed T-Cell Add-Back

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

Primary Outcome Measures:
  • Overall survival at day 200 [ Designated as safety issue: No ]
  • Nonrelapse mortality rate at day 200 [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Nonhematologic toxicity [ Designated as safety issue: Yes ]
  • Incidence and severity of acute and chronic graft-versus-host disease [ Designated as safety issue: No ]
  • Relapse of disease [ Designated as safety issue: No ]
  • Disease-free survival [ Designated as safety issue: No ]

Estimated Enrollment: 68
Study Start Date: September 2006
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Determine the overall survival rate at day 200 in patients with hematologic cancers or other diseases who undergo allogeneic peripheral blood stem cell transplantation using the CliniMACS® CD34 Reagent System for T-cell depletion followed by delayed T-cell add-back.
  • Determine the safety of this regimen, in terms of the nonrelapse mortality rate at day 200, in these patients.

OUTLINE:

  • Myeloablative preparative regimen: Patients receive fludarabine phosphate IV over 30 minutes on days -8 to -4 and cyclophosphamide IV over 1 hour on days -3 and -2. Patients also undergo high-dose* total body irradiation (TBI) twice daily on days -7 to -4.

NOTE: *Patients over 55 years of age receive reduced-dose TBI.

  • Allogeneic peripheral blood stem cell (PBSC) transplantation: Patients receive T-cell-depleted (via the CliniMACS® CD34 Reagent System), filgrastim (G-CSF)-mobilized, donor PBSC IV over 4 hours on day 0.
  • Graft-versus-host-disease (GVHD) prophylaxis: Patients receive cyclosporine (or tacrolimus) IV or orally twice daily on days -6 to 21, and then again beginning on day 89 and continuing up to day 150, followed by a slow taper to day 180, in the absence of GVHD.
  • Donor lymphocyte infusion (DLI): Patients receive delayed T-cell add-backs of donor lymphocytes IV over 1 hour on day 90. If relapse occurs, patients may receive DLI before day 90 or as a repeat infusion.

After completion of study therapy, patients are followed periodically for 3 years.

  Eligibility

Ages Eligible for Study:   10 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of 1 of the following:

    • Chronic myelogenous leukemia (CML), meeting 1 of the following criteria:

      • Under 21 years of age and in chronic phase
      • Ten to 75 years of age with CML in chronic phase, meeting 1 of the following criteria:

        • Failed or intolerant to prior treatment with imatinib mesylate
        • No prior therapeutic doses of imatinib mesylate within 12 months after disease diagnosis
      • Ten to 75 years of age with CML in accelerated phase or blast transformation
    • Acute lymphoblastic leukemia, meeting 1 of the following criteria:

      • In first remission with any of the following high-risk features:

        • WBC > 100,000/mm³ at diagnosis
        • Karyotypes t9; 22, t4, t19, t11, or biphenotypic leukemia
      • In second or subsequent remission
      • Primary induction failure
      • Partially responding or untreated relapsed disease
    • Acute myeloid leukemia (AML), meeting 1 of the following criteria:

      • In first remission

        • No AML with good-risk karyotypes (e.g., M3 [t15; 17], M4Eo [inv 16], t [8; 21])
      • In second or subsequent remission
      • Primary induction failure
      • Resistant relapsed disease
    • Myelodysplastic syndromes (MDS), including any of the following subtypes:

      • Refractory anemia with transfusion dependence
      • Refractory anemia with excess blasts
      • MDS in transformation to acute leukemia
      • Chronic myelomonocytic leukemia
      • Atypical MDS/myeloproliferative disorders
    • Myeloproliferative disorders, including any of the following subtypes:

      • Atypical (Philadelphia chromosome negative) chronic myelogenous or neutrophilic leukemias
      • Progressing myelofibrosis
      • Polycythemia vera
      • Essential thrombocythemia in transformation to acute leukemia
      • Essential thrombocythemia with progressive transfusion requirements or pancytopenia
    • Chronic lymphocytic leukemia

      • Refractory to fludarabine phosphate treatment AND meets 1 of the following criteria:

        • Bulky progressive disease
        • Thrombocytopenia (i.e., platelet count ≤ 100,000/mm^3) not due to recent chemotherapy
        • Anemia (i.e., hemoglobin ≤ 10 g/dL) not due to recent chemotherapy
    • Non-Hodgkin's lymphoma, including mantle cell lymphoma, that has relapsed or is refractory to standard-of-care treatments
    • Multiple myeloma or Waldenstrom's macroglobulinemia that is unresponsive to or relapsed after standard-of-care treatments
  • HLA-identical (6/6) related donor available

PATIENT CHARACTERISTICS:

  • Life expectancy ≥ 3 months
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No major anticipated illness or organ failure incompatible with survival from transplantation
  • No severe psychiatric illness or mental deficiency that would preclude study compliance
  • HIV negative
  • DLCO ≥ 65% of predicted
  • LVEF ≥ 40%
  • AST ≤ 20 times upper limit of normal (ULN)
  • Bilirubin ≤ 10 times ULN
  • Creatinine ≤ 6 times ULN

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior allogeneic stem cell transplantation
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00398346

Locations
United States, Maryland
NIH - Warren Grant Magnuson Clinical Center Recruiting
Bethesda, Maryland, United States, 20892-1182
Contact: Clinical Trials Office - NIH - Warren Grant Magnuson Clinical     800-411-1222        
Sponsors and Collaborators
Investigators
Study Chair: Aarthi Shenoy, MD National Heart, Lung, and Blood Institute (NHLBI)
  More Information

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

Responsible Party: NHLBI - Hematology Branch ( Aarthi Shenoy )
Study ID Numbers: CDR0000512813, NHLBI-06-H-0248, NHLBI-IDE-13058
Study First Received: November 9, 2006
Last Updated: November 25, 2008
ClinicalTrials.gov Identifier: NCT00398346  
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
graft versus host disease
secondary myelofibrosis
de novo myelodysplastic syndromes
Philadelphia chromosome negative chronic myelogenous leukemia
refractory anemia with excess blasts
refractory anemia
refractory anemia with excess blasts in transformation
previously treated myelodysplastic syndromes
atypical chronic myeloid leukemia
chronic neutrophilic leukemia
chronic idiopathic myelofibrosis
polycythemia vera
essential thrombocythemia
stage III multiple myeloma
refractory multiple myeloma
Waldenstrom macroglobulinemia
refractory chronic lymphocytic leukemia
childhood chronic myelogenous leukemia
relapsing chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
adult acute myeloid leukemia in remission
recurrent adult acute myeloid leukemia
childhood acute myeloid leukemia in remission
recurrent childhood acute myeloid leukemia
secondary acute myeloid leukemia

Study placed in the following topic categories:
Philadelphia Chromosome
Blast Crisis
Cyclosporine
Chronic myelogenous leukemia
Refractory anemia
Lymphoma, small cleaved-cell, diffuse
Tacrolimus
Cyclosporins
Ileal Diseases
Small non-cleaved cell lymphoma
Lymphoma, large-cell, immunoblastic
Lymphomatoid granulomatosis
Preleukemia
Hemorrhagic Disorders
Hemorrhagic thrombocythemia
Neoplasm Metastasis
Thrombocythemia, Hemorrhagic
Myelodysplastic syndromes
Essential thrombocytosis
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Hematologic Diseases
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
Leukemia, Myelomonocytic, Chronic
Blood Coagulation Disorders
Acute myelogenous leukemia
Leukemia, Myeloid
Myelodysplastic myeloproliferative disease
Waldenstrom Macroglobulinemia
Leukemia, Myeloid, Accelerated Phase
B-cell lymphomas

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Neoplasms by Site
Pathologic Processes
Jejunal Diseases
Syndrome
Therapeutic Uses
Antifungal Agents
Cardiovascular Diseases
Alkylating Agents
Dermatologic Agents
Disease
Neoplasms by Histologic Type
Immune System Diseases
Enzyme Inhibitors
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents

ClinicalTrials.gov processed this record on January 16, 2009