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

Primary Purpose

Chronic Myeloproliferative Disorders, Graft Versus Host Disease, Leukemia

Status
Active
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
busulfan
cyclophosphamide
cyclosporine
etoposide
fludarabine phosphate
melphalan
methotrexate
mycophenolate mofetil
sirolimus
tacrolimus
allogeneic hematopoietic stem cell transplantation
peripheral blood stem cell transplantation
total-body irradiation
Sponsored by
City of Hope Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Myeloproliferative Disorders focused on measuring 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, chronic idiopathic myelofibrosis, chronic neutrophilic leukemia, essential thrombocythemia, polycythemia vera, Waldenstrom macroglobulinemia, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, recurrent adult Burkitt lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, splenic marginal zone lymphoma, recurrent childhood grade III lymphomatoid granulomatosis, childhood nasal type extranodal NK/T-cell lymphoma, recurrent childhood large cell lymphoma, childhood diffuse large cell lymphoma, childhood immunoblastic large cell lymphoma, recurrent childhood lymphoblastic lymphoma, Burkitt lymphoma, recurrent childhood small noncleaved cell lymphoma, anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, recurrent adult T-cell leukemia/lymphoma, recurrent adult grade III lymphomatoid granulomatosis, adult nasal type extranodal NK/T-cell lymphoma, recurrent adult Hodgkin lymphoma, recurrent/refractory childhood Hodgkin lymphoma, refractory chronic lymphocytic leukemia, refractory multiple myeloma, stage III multiple myeloma, aplastic anemia, paroxysmal nocturnal hemoglobinuria, adult acute lymphoblastic leukemia in remission, childhood acute lymphoblastic leukemia in remission, recurrent cutaneous T-cell non-Hodgkin lymphoma, recurrent mycosis fungoides/Sezary syndrome, stage II multiple myeloma

Eligibility Criteria

0 Years - 120 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm 5

    Arm 6

    Arm Type

    Active Comparator

    Active Comparator

    Active Comparator

    Active Comparator

    Active Comparator

    Active Comparator

    Arm Label

    Regimen I

    Regimen II

    Regimen III

    Regimen IV

    Regimen V

    Regimen VI

    Arm Description

    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.

    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.

    Patients undergo TBI on days -7 to -4 and receive etoposide IV on day -3.

    Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3 and melphalan IV on day -2.

    Patients receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo TBI on day 0.

    Patients receive busulfan IV over 3 hours and fludarabine phosphate IV over 30 minutes on days -5 to -2.

    Outcomes

    Primary Outcome Measures

    Neutrophil Engraftment - The Days Till ANC Recovery
    The primary engraftment endpoint, neutrophil engraftment, is defined as the first of three consecutive days on which the absolute neutrophil count is > 500/µL. The duration and extent of neutrophil engraftment is the time from transplant to neutrophil engraftment.

    Secondary Outcome Measures

    Two-year Overall Survival
    Overall survival (OS) was measured from peripheral stem cell infusion to death from any cause. It was estimated using the Kaplan-Meier method; the 95% confidence interval was calculated using Greenwood's formula. Participants were followed up to 2 years after transplant and Kaplan-Meier survival analysis was used to generate the two-year Overall Survival estimate presented.

    Full Information

    First Posted
    October 13, 2007
    Last Updated
    July 24, 2023
    Sponsor
    City of Hope Medical Center
    Collaborators
    National Cancer Institute (NCI)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00544115
    Brief Title
    Donor Peripheral Stem Cell Transplant in Treating Patients With Advanced Hematologic Cancer or Other Disorders
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2023
    Overall Recruitment Status
    Active, not recruiting
    Study Start Date
    October 16, 2001 (Actual)
    Primary Completion Date
    March 13, 2007 (Actual)
    Study Completion Date
    December 30, 2023 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    City of Hope Medical Center
    Collaborators
    National Cancer Institute (NCI)

    4. Oversight

    5. Study Description

    Brief Summary
    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.
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Chronic Myeloproliferative Disorders, Graft Versus Host Disease, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases, Precancerous/Nonmalignant Condition
    Keywords
    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, chronic idiopathic myelofibrosis, chronic neutrophilic leukemia, essential thrombocythemia, polycythemia vera, Waldenstrom macroglobulinemia, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, recurrent adult Burkitt lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, splenic marginal zone lymphoma, recurrent childhood grade III lymphomatoid granulomatosis, childhood nasal type extranodal NK/T-cell lymphoma, recurrent childhood large cell lymphoma, childhood diffuse large cell lymphoma, childhood immunoblastic large cell lymphoma, recurrent childhood lymphoblastic lymphoma, Burkitt lymphoma, recurrent childhood small noncleaved cell lymphoma, anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, recurrent adult T-cell leukemia/lymphoma, recurrent adult grade III lymphomatoid granulomatosis, adult nasal type extranodal NK/T-cell lymphoma, recurrent adult Hodgkin lymphoma, recurrent/refractory childhood Hodgkin lymphoma, refractory chronic lymphocytic leukemia, refractory multiple myeloma, stage III multiple myeloma, aplastic anemia, paroxysmal nocturnal hemoglobinuria, adult acute lymphoblastic leukemia in remission, childhood acute lymphoblastic leukemia in remission, recurrent cutaneous T-cell non-Hodgkin lymphoma, recurrent mycosis fungoides/Sezary syndrome, stage II multiple myeloma

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    260 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Regimen I
    Arm Type
    Active Comparator
    Arm Description
    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.
    Arm Title
    Regimen II
    Arm Type
    Active Comparator
    Arm Description
    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.
    Arm Title
    Regimen III
    Arm Type
    Active Comparator
    Arm Description
    Patients undergo TBI on days -7 to -4 and receive etoposide IV on day -3.
    Arm Title
    Regimen IV
    Arm Type
    Active Comparator
    Arm Description
    Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3 and melphalan IV on day -2.
    Arm Title
    Regimen V
    Arm Type
    Active Comparator
    Arm Description
    Patients receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo TBI on day 0.
    Arm Title
    Regimen VI
    Arm Type
    Active Comparator
    Arm Description
    Patients receive busulfan IV over 3 hours and fludarabine phosphate IV over 30 minutes on days -5 to -2.
    Intervention Type
    Drug
    Intervention Name(s)
    busulfan
    Intervention Type
    Drug
    Intervention Name(s)
    cyclophosphamide
    Intervention Type
    Drug
    Intervention Name(s)
    cyclosporine
    Intervention Type
    Drug
    Intervention Name(s)
    etoposide
    Intervention Type
    Drug
    Intervention Name(s)
    fludarabine phosphate
    Intervention Type
    Drug
    Intervention Name(s)
    melphalan
    Intervention Type
    Drug
    Intervention Name(s)
    methotrexate
    Intervention Type
    Drug
    Intervention Name(s)
    mycophenolate mofetil
    Intervention Type
    Drug
    Intervention Name(s)
    sirolimus
    Intervention Type
    Drug
    Intervention Name(s)
    tacrolimus
    Intervention Type
    Procedure
    Intervention Name(s)
    allogeneic hematopoietic stem cell transplantation
    Intervention Type
    Procedure
    Intervention Name(s)
    peripheral blood stem cell transplantation
    Intervention Type
    Radiation
    Intervention Name(s)
    total-body irradiation
    Primary Outcome Measure Information:
    Title
    Neutrophil Engraftment - The Days Till ANC Recovery
    Description
    The primary engraftment endpoint, neutrophil engraftment, is defined as the first of three consecutive days on which the absolute neutrophil count is > 500/µL. The duration and extent of neutrophil engraftment is the time from transplant to neutrophil engraftment.
    Time Frame
    Up to 180 days post transplant
    Secondary Outcome Measure Information:
    Title
    Two-year Overall Survival
    Description
    Overall survival (OS) was measured from peripheral stem cell infusion to death from any cause. It was estimated using the Kaplan-Meier method; the 95% confidence interval was calculated using Greenwood's formula. Participants were followed up to 2 years after transplant and Kaplan-Meier survival analysis was used to generate the two-year Overall Survival estimate presented.
    Time Frame
    Up to 2 years post transplant

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    0 Years
    Maximum Age & Unit of Time
    120 Years
    Accepts Healthy Volunteers
    No
    Eligibility 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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Auayporn P. Nademanee, MD
    Organizational Affiliation
    City of Hope Comprehensive Cancer Center
    Official's Role
    Study Chair

    12. IPD Sharing Statement

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

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