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Trial record 20 of 23 for:    "Al Amyloidosis" | "Cyclophosphamide"

Non-Ablative Allo HSCT For Hematologic Malignancies or SAA

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00006379
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : December 8, 2011
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Case Comprehensive Cancer Center

Brief Summary:

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy used to kill cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy followed by peripheral stem cell transplantation in treating patients who have hematologic cancer or aplastic anemia.

Condition or disease Intervention/treatment Phase
Chronic Myeloproliferative Disorders Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases Precancerous/Nonmalignant Condition Small Intestine Cancer Biological: anti-thymocyte globulin Biological: graft-versus-tumor induction therapy Drug: cyclophosphamide Drug: fludarabine phosphate Procedure: peripheral blood stem cell transplantation Phase 2

Detailed Description:


  • Determine the rates of durable full donor hematologic engraftment in patients with high-risk hematologic malignancies or severe aplastic anemia treated with non-myeloablative conditioning using fludarabine, cyclophosphamide, and anti-thymocyte globulin followed by allogeneic peripheral blood stem cell transplantation.
  • Determine the acute and delayed toxic effects of this non-myeloablative conditioning regimen in this patient population.
  • Determine the event-free and overall survival of patients treated with this regimen.
  • Determine the incidence and severity of acute and chronic graft-versus-host disease in patients treated with this regimen.
  • Determine the rate and quality of immune reconstitution in patients treated with this regimen.
  • Determine the rate of disease relapse and incidence of post-transplantation lymphoproliferative disease in these patients.

OUTLINE: Patients are stratified according to disease category (malignant vs non-malignant) and graft source (unrelated vs HLA-matched sibling).

Beginning at least 4 weeks after conventional-dose chemotherapy, patients receive non-myeloablative conditioning comprising fludarabine IV over 30 minutes on days -8 to -4, cyclophosphamide IV over 2 hours on days -3 to -2, and anti-thymocyte globulin IV over at least 4 hours on days -2 and -1. Patients undergo filgrastim (G-CSF)-mobilized allogeneic peripheral blood stem cell transplantation on day 0.

Patients are followed weekly for 3 months, every 2 weeks for 3 months, monthly for 6 months, and then every 2 months thereafter.

PROJECTED ACCRUAL: A minimum of 30 patients will be accrued for this study within 4 years.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 58 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Purine-Analog-Containing Non-Myeloablative Allogeneic Stem Cell Transplantation for Treatment of Hematologic Malignancies and Severe Aplastic Anemia
Study Start Date : June 2000
Actual Primary Completion Date : January 2004
Actual Study Completion Date : October 2011

Intervention Details:
  • Biological: anti-thymocyte globulin
    anti-thymocyte globulin IV over at least 4 hours on days -2 and -1
  • Biological: graft-versus-tumor induction therapy
    Patients undergo filgrastim (G-CSF)-mobilized allogeneic peripheral blood stem cell transplantation on day 0.
  • Drug: cyclophosphamide
    cyclophosphamide IV over 2 hours on days -3 to -2
  • Drug: fludarabine phosphate
    fludarabine IV over 30 minutes on days -8 to -4
  • Procedure: peripheral blood stem cell transplantation
    Patients undergo filgrastim (G-CSF)-mobilized allogeneic peripheral blood stem cell transplantation on day 0.

Primary Outcome Measures :
  1. Evaluation of Donor Engraftment [ Time Frame: at 28 days ]
    Peripheral blood from the donor and patient is obtained for chimerism studies. The primary analysis will consist of estimating the graft failure proportions for each of the separate patient groups and calculating confidence intervals for these proportions. This analysis will be done conditional on patients surviving at least 28 days.

Secondary Outcome Measures :
  1. Stable donor hematopoietic chimerism [ Time Frame: at day 100 ]
    Number of Patients Transplanted More Than 100 Days Ago

  2. Event free and overall survival [ Time Frame: to progression/death ]

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Ages Eligible for Study:   up to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically proven high-risk hematologic malignancy

    • Acute non-lymphocytic leukemia (ANLL) after induction failure, or in first complete remission (CR) with high-risk features, including any of the following:

      • Stem cell or biphenotypic classification (AML-M0)
      • Erythroleukemia (AML-M6)
      • Acute megakaryocytic leukemia (AML-M7)
      • Cytogenetic markers indicative of poor prognosis
      • Failure to achieve CR after standard induction therapy
    • Acute lymphocytic leukemia (ALL) or ANLL in relapse or second or subsequent remission
    • Chronic myelogenous leukemia (CML) in chronic or accelerated phase

      • Patients with CML in blast crisis are eligible after reinduction chemotherapy places them in chronic phase
    • High-risk ALL in first CR with high risk defined by presence of t(4;11), t(9;22) translocation, hyperleukocytosis (initial WBC greater than 30,000/mm^3), or failure to achieve CR by day 28 after standard induction

      • No T-cell ALL or t(8;14) positive B-cell ALL in first remission with hyperleukocytosis
    • Myelodysplastic syndrome by peripheral blood smear and bone marrow examination

      • Refractory to medical management OR
      • Cytogenetic abnormalities predictive of transformation into acute leukemia including 5q-, 7q-, monosomy 7, and trisomy 8 OR
      • Evidence of evolution to AML (e.g., refractory anemia with excess blasts (RAEB) or RAEB in transformation)
    • Multiple myeloma, non-Hodgkin's lymphoma (NHL), ANLL, or ALL with recurrent disease after autologous stem cell transplantation (SCT)

      • At least 3 months since prior autologous SCT
    • Hodgkin's lymphoma, NHL, or multiple myeloma beyond first CR or primary induction failures whose disease has demonstrated sensitivity to pre-transplantation cytoreduction (defined as greater than 50% reduction in tumor burden)

      • Mantle zone NHL allowed after induction therapy
    • Myeloproliferative disorder that is non-responsive to medical management and requires allografting, unless evidence of grade 3 or worse myelofibrosis on marrow biopsy OR
  • Histologically proven acquired severe aplastic anemia (SAA) that is recurrent or unresponsive after anti-thymocyte globulin and/or cyclosporine

    • SAA defined by at least 2 of the following conditions:

      • Granulocyte count less than 500/mm^3
      • Platelet count less than 20,000/mm^3
      • Absolute reticulocyte count less than 20,000/mm^3 after correction for hematocrit
  • Ineligible for full ablative conditioning due to any of the following conditions:

    • Prior extensive therapy (more than 2 salvage chemotherapy regimens and/or autologous transplantation)
    • Over age 55 OR
    • Under age 55 with comorbid disease (e.g., suboptimal cardiac, pulmonary, or renal function and/or prior life-threatening infection)
  • HLA-A, B, and DR phenotypically identical sibling donor OR
  • HLA-A, B, and DR identical genetically matched unrelated donor
  • No ANLL in first CR (less than 5% blasts in marrow) with translocations t(8;21) and inv(16) unless failed first-line induction therapy OR
  • No ANLL in first CR (less than 5% blasts in marrow) with translocations t(15;17) abnormality unless failed first-line induction therapy OR molecular evidence of persistent disease
  • No active CNS disease



  • 0 to 70

Performance status:

  • Zubrod 0-1
  • Karnofsky 80-100%

Life expectancy:

  • At least 3 months


  • See Disease Characteristics


  • ALT/AST no greater than 4 times normal
  • Bilirubin no greater than 2.0 mg/dL


  • See Disease Characteristics
  • Creatinine clearance at least 50 mL/min


  • See Disease Characteristics
  • Shortening fraction or ejection fraction at least 40% of normal for age by echocardiogram or radionuclide scan
  • No clinically significant comorbid illnesses (e.g., myocardial infarction or cerebrovascular accident)


  • See Disease Characteristics
  • FVC and FEV_1 at least 60% of predicted for age
  • DLCO at least 60% of predicted for adults


  • No severe neurosensory symptoms (i.e., peripheral neuropathy)
  • HIV negative
  • Active infection allowed if controlled by appropriate drug therapy
  • Not pregnant or nursing
  • Negative pregnancy test


Biologic therapy:

  • See Disease Characteristics


  • See Disease Characteristics

Endocrine therapy:

  • Not specified


  • Not specified


  • Not specified


  • Recovered from prior therapy
  • No concurrent investigational agents unless approved by protocol investigators

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00006379

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United States, Ohio
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-5065
Sponsors and Collaborators
Case Comprehensive Cancer Center
National Cancer Institute (NCI)
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Principal Investigator: Tamila Kindwall-Keller, DO Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

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Responsible Party: Case Comprehensive Cancer Center Identifier: NCT00006379     History of Changes
Other Study ID Numbers: CWRU3Y00
P30CA043703 ( U.S. NIH Grant/Contract )
CWRU-3Y00 ( Other Identifier: Case Comprehensive Cancer Center )
05-00-07 ( Other Identifier: University Hospitals IRB )
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: December 8, 2011
Last Verified: December 2011
Keywords provided by Case Comprehensive Cancer Center:
primary systemic amyloidosis
monoclonal gammopathy of undetermined significance
recurrent childhood acute lymphoblastic leukemia
recurrent adult Hodgkin lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
isolated plasmacytoma of bone
extramedullary plasmacytoma
refractory multiple myeloma
Waldenstrom macroglobulinemia
recurrent childhood lymphoblastic lymphoma
recurrent childhood acute myeloid leukemia
recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
relapsing chronic myelogenous leukemia
small intestine lymphoma
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
childhood acute myeloid leukemia in remission
childhood acute lymphoblastic leukemia in remission
polycythemia vera
chronic idiopathic myelofibrosis
essential thrombocythemia
adult acute erythroid leukemia (M6)
adult acute megakaryoblastic leukemia (M7)
childhood acute erythroleukemia (M6)
childhood acute megakaryocytic leukemia (M7)
recurrent/refractory childhood Hodgkin lymphoma
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Intestinal Neoplasms
Precancerous Conditions
Myelodysplastic Syndromes
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Pathologic Processes
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Bone Marrow Diseases
Gastrointestinal Neoplasms
Digestive System Neoplasms