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Donor Peripheral Stem Cell Transplant in Treating Patients With Advanced Hematologic Cancer or Other Disorders

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT00544115
First received: October 13, 2007
Last updated: December 16, 2013
Last verified: December 2013
  Purpose

RATIONALE: Giving chemotherapy and total-body irradiation before a donor peripheral 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. Giving tacrolimus, methotrexate, cyclosporine, mycophenolate mofetil, and sirolimus before and after transplant may stop this from happening.

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


Condition Intervention Phase
Chronic Myeloproliferative Disorders
Graft Versus Host Disease
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Diseases
Precancerous/Nonmalignant Condition
Drug: busulfan
Drug: cyclophosphamide
Drug: cyclosporine
Drug: etoposide
Drug: fludarabine phosphate
Drug: melphalan
Drug: methotrexate
Drug: mycophenolate mofetil
Drug: sirolimus
Drug: tacrolimus
Procedure: allogeneic hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation
Radiation: total-body irradiation
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Allogeneic Peripheral Blood Stem Cell Transplantation From Matched Unrelated Donors in Patients With Advanced Hematologic Malignancies and Hematological Disorders

Resource links provided by NLM:

Genetic and Rare Diseases Information Center resources: Acute Lymphoblastic Leukemia Acute Lymphoblastic Leukemia, Childhood Acute Myelocytic Leukemia Acute Myeloid Leukemia, Adult Acute Myeloid Leukemia, Childhood Acute Non Lymphoblastic Leukemia Anaplastic Large Cell Lymphoma Anaplastic Plasmacytoma Angioimmunoblastic Lymphadenopathy With Dysproteinemia Angioimmunoblastic T-cell Lymphoma Aplastic Anemia B-cell Lymphomas Burkitt Lymphoma Chronic Lymphocytic Leukemia Chronic Myeloid Leukemia Chronic Myelomonocytic Leukemia Chronic Myeloproliferative Disorders Chronic Neutrophilic Leukemia Cutaneous T-cell Lymphoma Essential Thrombocythemia Follicular Lymphoma Hodgkin Lymphoma Hodgkin Lymphoma, Childhood Homologous Wasting Disease Hypereosinophilic Syndrome Juvenile Myelomonocytic Leukemia Leukemia, B-cell, Chronic Leukemia, Myeloid Leukemia, T-cell, Chronic Lymphoblastic Lymphoma Lymphoma, Large-cell Lymphoma, Large-cell, Immunoblastic Lymphoma, Small Cleaved-cell, Diffuse Lymphomatoid Granulomatosis Lymphosarcoma Mantle Cell Lymphoma Multiple Myeloma Mycosis Fungoides Myelodysplastic Syndromes Myelodysplastic/myeloproliferative Disease Myelofibrosis Paroxysmal Nocturnal Hemoglobinuria Plasmablastic Lymphoma Polycythemia Vera Sezary Syndrome Small Non-cleaved Cell Lymphoma Waldenstrom Macroglobulinemia
U.S. FDA Resources

Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Neutrophil and platelet engraftment [ Designated as safety issue: No ]
  • Incidence of acute and chronic graft-versus-host disease (GVHD) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Impact of HLA class I and class II allele-matching on the incidence of GVHD and on the survival outcome [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Disease-free survival [ Designated as safety issue: No ]
  • Relapse [ Designated as safety issue: No ]

Estimated Enrollment: 260
Study Start Date: September 2001
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • To evaluate hematopoietic recovery, using neutrophil and platelet engraftment as the primary criterion, in patients with advanced hematologic malignancies or other disorders undergoing allogeneic peripheral blood stem cell (PBSC) transplantation from matched unrelated donors.
  • To evaluate the incidence of acute and chronic graft-versus-host-disease (GVHD) in patients undergoing allogeneic PBSC transplantation from matched unrelated donors.

Secondary

  • To evaluate the impact of HLA class I and class II allele-matching on the incidence of GVHD and on the survival outcome of these patients.
  • To evaluate overall survival, disease-free survival, and relapse in these patients.

OUTLINE: Patients are stratified according to type of conditioning regimen (myeloablative vs reduced-intensity myeloablative). Patients are assigned to a conditioning regimen according to diagnosis, age, disease status, prior radiotherapy, and prior autologous stem cell transplantation.

  • Conditioning regimen:

    • Regimen I: Patients undergo total body irradiation (TBI) on days -7 to -4 and receive cyclophosphamide IV on days -3 and -2. Alternatively, patients may receive cyclophosphamide on days -7 and -6 and undergo TBI on days -4 to -1.
    • Regimen II: Patients receive busulfan IV over 2 hours once on day -8 and then every 6 hours on days -7 to -4. Patients also receive cyclophosphamide IV on days -3 and -2.
    • Regimen III: Patients undergo TBI on days -7 to -4 and receive etoposide IV on day -3.
    • Regimen IV: Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3 and melphalan IV on day -2.
    • Regimen V: Patients receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo TBI on day 0.
    • Regimen VI: Patients receive busulfan IV over 3 hours and fludarabine phosphate IV over 30 minutes on days -5 to -2.
  • Allogeneic peripheral blood stem cell (PBSC) transplantation: All patients undergo allogeneic PBSC transplantation on day 0.
  • Graft-versus-host disease (GVHD) prophylaxis: Patients receive one of the following GVHD prophylaxis regimens:

    • Regimen A: Patients receive tacrolimus IV or orally on days -1 to 180 and methotrexate IV on days 1, 3, 6, and 11.
    • Regimen B: Patients receive cyclosporine IV or orally twice daily on days -1 to 180, mycophenolate mofetil IV over 2 hours or orally twice daily on days 0-27, and methotrexate IV on days 1, 3, and 6.
    • Regimen C: Patients receive tacrolimus IV continuously or orally, and oral sirolimus beginning on day -3. Patients also receive methotrexate IV on days 1, 3, and 6.

After completion of study therapy, patients are followed periodically.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of one of the following:

    • Acute lymphocytic leukemia (ALL), meeting one of the following criteria:

      • In first relapse or beyond
      • High-risk ALL, defined by any of the following:

        • Hypoploidy (≤ 44 chromosomes)
        • Pseudodiploidy with translocations or molecular evidence of t(9;22), 11q23, or t(8;14), excluding B-cell ALL
        • Elevated WBC at presentation (WBC > 20,000/mm³ [for patients > 18 years of age]; WBC > 200,000/mm³ [for patients 12-18 years of age])
    • Acute myeloid leukemia (AML), meeting one of the following criteria:

      • In first complete remission
      • Failed to achieve remission
      • In first relapse or beyond
      • Secondary AML (> 30% blasts in marrow aspirate)

        • Should receive induction chemotherapy to obtain remission, if possible, before transplant
    • Chronic myelogenous leukemia, meeting one of the following criteria:

      • In first or second chronic phase or accelerated phase
      • In blast crisis, defined as > 30% promyelocytes plus blasts in the bone marrow
    • Myelodysplastic syndromes, including any of the following:

      • Refractory anemia with excess blasts (RAEB)
      • Chronic myelomonocytic leukemia
      • RAEB in transformation
    • Refractory non-Hodgkin lymphoma, chronic lymphocytic leukemia, Hodgkin lymphoma, or multiple myeloma

      • Received and failed front-line therapy, high-dose therapy and autologous stem cell transplantation, or salvage therapy
    • Myeloproliferative disorders/myelofibrosis may be allowed on a case by case basis
    • Severe aplastic anemia, paroxysmal nocturnal hemoglobinuria, or any other hematologic disorder requiring transplantation
  • Patients > 55 years of age with hematologic diseases treatable by allogeneic stem cell transplantation who are not eligible for IRB 99190 are eligible
  • No uncontrolled CNS involvement of disease
  • No matched (6/6) related donor available
  • HLA-identical unrelated donor available

    • HLA-phenotypically identical for HLA-A and HLA-B alleles and identical for DRB1 alleles by DNA typing for both class I and class II antigens

      • Allele mismatch for HLA class I (i.e., B 2701 vs B 2702) allowed if no alternative donors
      • Allele mismatch for class II (i.e., DRB1 0401 vs 0402) or minor mismatch for class I cross reactive group (CREG) (i.e., A 2 vs A 28) allowed in patients ≤ 35 years of age requiring urgent transplant

PATIENT CHARACTERISTICS:

  • Karnofsky performance status 50-100%
  • Life expectancy > 8 weeks
  • LVEF ≥ 45% at rest
  • AST ≤ 2 times normal (unless liver function abnormality is due to underlying disease)
  • Total bilirubin < 1.5 times normal (unless liver function abnormality is due to underlying disease)
  • Creatinine ≤ 1.5 times normal OR creatinine clearance ≥ 60 mL/min
  • DLCO ≥ 40% of predicted (corrected for hemoglobin)
  • No coexisting medical problem that would significantly increase the risk of the transplant procedure
  • HIV negative
  • Not pregnant

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  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: NCT00544115

Sponsors and Collaborators
City of Hope Medical Center
Investigators
Study Chair: Auayporn P. Nademanee, MD Beckman Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT00544115     History of Changes
Other Study ID Numbers: 01089, P30CA033572, CHNMC-01089, 01089, CDR0000566376
Study First Received: October 13, 2007
Last Updated: December 16, 2013
Health Authority: United States: Federal Government

Keywords provided by City of Hope Medical Center:
graft versus host disease
recurrent adult acute lymphoblastic leukemia
recurrent childhood acute lymphoblastic leukemia
untreated adult acute lymphoblastic leukemia
untreated childhood acute lymphoblastic leukemia
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
refractory anemia with excess blasts in transformation
refractory anemia with excess blasts
atypical chronic myeloid leukemia
chronic myelomonocytic leukemia
juvenile myelomonocytic leukemia
myelodysplastic/myeloproliferative disease, unclassifiable
recurrent adult acute myeloid leukemia
recurrent childhood acute myeloid leukemia
adult acute myeloid leukemia in remission
childhood acute myeloid leukemia in remission
secondary acute myeloid 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)
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
childhood chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
relapsing chronic myelogenous leukemia
chronic eosinophilic leukemia

Additional relevant MeSH terms:
Disease
Graft vs Host Disease
Leukemia
Lymphoma
Multiple Myeloma
Myelodysplastic Syndromes
Myelodysplastic-Myeloproliferative Diseases
Myeloproliferative Disorders
Neoplasms, Plasma Cell
Plasmacytoma
Precancerous Conditions
Preleukemia
Syndrome
Blood Protein Disorders
Bone Marrow Diseases
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Pathologic Processes
Vascular Diseases
Cyclophosphamide
Fludarabine

ClinicalTrials.gov processed this record on November 20, 2014