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Combination Chemotherapy Followed By Umbilical Cord Blood Transplantation in Treating Patients With Hematologic Cancer or Severe Aplastic Anemia
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), December 2008
Sponsors and Collaborators: Case Comprehensive Cancer Center
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00054236
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Umbilical cord blood transplantation may be able to replace cells destroyed by chemotherapy.

PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy followed by umbilical cord blood transplantation in treating patients who have hematologic cancer or severe aplastic anemia.


Condition Intervention Phase
Chronic Myeloproliferative Disorders
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Diseases
Drug: anti-thymocyte globulin
Drug: cyclophosphamide
Drug: filgrastim
Drug: fludarabine phosphate
Procedure: umbilical cord blood transplantation
Phase I

Genetics Home Reference related topics: aceruloplasminemia hemophilia
MedlinePlus related topics: Anemia Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood Lymphoma Multiple Myeloma
Drug Information available for: Cyclophosphamide Filgrastim Fludarabine Fludarabine monophosphate
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment
Official Title: Pilot Study Of Multiple Umbilical Cord Blood Unit Transplantation Following Non-Myeloablative Conditioning In Patients With Hematologic Disorders Or Severe Aplastic Anemia

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

Primary Outcome Measures:
  • Event-free survival by disease assessment at 28 and 100 days and then at 6, 9, 12, 18, and 24 months [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Umbilical cord blood donor engraftment by chimerism and complete blood count (CBC) monthly for 6 months and then at 9, 12, 18, and 24 months [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: May 2002
Estimated Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Determine the incidence and severity of acute toxicity in patients with hematologic malignancies or severe aplastic anemia treated with a non-myeloablative conditioning regimen followed by umbilical cord blood transplantation.
  • Determine the incidence and severity of acute and chronic graft-versus-host-disease in patients treated with this regimen.
  • Determine the incidence of relapse, disease-free survival, and overall survival of patients treated with this regimen.
  • Determine the survival rate at 100 days post-transplantation in patients treated with this regimen.
  • Determine the incidence of regimen-related complications (infection, hepatic veno-occlusive disease, and interstitial pneumonitis) in patients treated with this regimen.
  • Determine the incidence of primary and secondary graft failure in patients treated with this regimen.
  • Determine the rates and kinetics of donor-derived lymphoid, myeloid, neutrophil, RBC, and platelet engraftment in patients treated with this regimen.

OUTLINE: Patients receive a non-myeloablative conditioning regimen 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 (ATG) IV over at least 4 hours on days -2 to -1. Patients unable to tolerate ATG may receive methylprednisolone IV over 1 hour on days -3 to -1.

Patients undergo multiple unit umbilical cord blood transplantation on days 0-1. Patients receive filgrastim (G-CSF) subcutaneously beginning on day 7 and continuing until blood counts recover.

Patients are followed monthly for 6 months; at 9, 12, 14, 16, 18, and 24 months; and then annually thereafter.

PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study within 2 years.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • One of the following histologically confirmed diagnoses:

    • Acquired severe aplastic anemia

      • Meets at least 2 of the following criteria:

        • 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)
      • Unresponsive to OR recurrent disease after prior treatment with anti-thymocyte globulin and/or cyclosporine
    • Acute myeloid leukemia (AML), meeting 1 of the following criteria:

      • Failed induction therapy
      • In first complete remission (CR) with any of the following high-risk features:

        • Stem cell or biphenotype classification (M0)
        • Erythroleukemia (M6)
        • Acute megakaryocytic leukemia (M7)
        • Cytogenetic markers indicative of poor prognosis
        • t(15;17) translocation and failed first-line induction therapy OR there is molecular evidence of persistent disease
        • t(8;21) and inv(16) translocations and failed first-line induction therapy
      • In early relapse*
      • In second or subsequent remission
      • Recurrent disease after prior autologous stem cell transplantation (SCT) NOTE: *No refractory relapse
    • Acute lymphoblastic leukemia, meeting 1 of the following criteria:

      • In early relapse*
      • In second or subsequent remission
      • In first CR with the following high-risk features:

        • t(4;11) or t(9;22) translocation
        • Hyperleukocytosis (initial WBC greater than 30,000/mm^3)
        • Failed to achieve CR by day 28 of standard induction therapy
      • Recurrent disease after prior autologous SCT NOTE: *No refractory relapse
    • Chronic myelogenous leukemia

      • Chronic or accelerated phase that has failed medical management
      • Blastic phase allowed after reinduction chemotherapy induces chronic phase
    • Myelodysplastic syndromes meeting 1 of the following criteria:

      • Refractory to medical management
      • Presence of cytogenetic abnormalities predictive of transformation to acute leukemia, including the following:

= 5q- = 7q-

  • Monosomy 7 and trisomy 8
  • Evidence of evolution to AML (e.g., refractory anemia with excess blasts [RAEB], or RAEB in transformation)

    • Chronic lymphocytic leukemia

      • Refractory to treatment including fludarabine-based therapy
      • Recurrent disease after prior autologous SCT
    • Multiple myeloma

      • Recurrent disease after prior autologous SCT
      • Beyond first CR or failed induction therapy
      • Disease is sensitive to pretransplantation cytoreduction
    • Hodgkin's lymphoma

      • Beyond first CR or failed induction therapy
      • Disease is sensitive to pretransplantation cytoreduction
    • Non-Hodgkin's lymphoma (NHL)

      • Recurrent disease after prior autologous SCT
      • Beyond first CR or failed induction therapy
      • Disease is sensitive to pretransplantation cytoreduction
      • Mantle zone NHL allowed after induction therapy
    • Myeloproliferative disorders

      • Refractory to medical management
      • Allografting required unless grade 3 or greater myelofibrosis by bone marrow biopsy

        • No HLA-matched sibling donor available
        • Ineligible for a myeloablative conditioning regimen due to advanced age (over 55), extensive prior therapy, and/or other comorbidities
        • If under age 55, must meet at least 1 of the following criteria:
    • Received extensive prior therapy
    • Organ toxicity or infection precluding eligibility for allogeneic transplantation with full ablation conditioning

      • Availability of 2-5 umbilical cord blood units that are at least a 4/6 HLA match
      • No active CNS disease
      • No primary or grade 3 or 4 myelofibrosis

PATIENT CHARACTERISTICS:

Age

  • Any age

Performance status

  • Karnofsky 70-100% (for patients 16 years of age and older)
  • Lansky 50-100% (for patients under 16 years of age)

Life expectancy

  • At least 3 months

Hematopoietic

  • See Disease Characteristics

Hepatic

  • ALT/AST less than 4 times normal
  • Bilirubin less than 2.0 mg/dL (unless due to hepatic infiltration by primary malignancy)

Renal

  • Creatinine clearance greater than 40 mL/min

Cardiovascular

  • Shortening fraction or ejection fraction greater than 40% of normal value for age by echocardiogram or radionuclide scan

Pulmonary

  • FVC and FEV_1 greater than 60% of predicted
  • DLCO greater than 60% of predicted (adult patients)
  • Clearance by pulmonologist required if patient cannot perform pulmonary function tests

Other

  • Not pregnant or nursing
  • No uncontrolled active infection (viral, bacterial, or fungal)
  • HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • See Disease Characteristics
  • More than 3 months since prior autologous stem cell transplantation

Chemotherapy

  • See Disease Characteristics
  • At least 4 weeks since prior chemotherapy

Endocrine therapy

  • Not specified

Radiotherapy

  • Not specified

Surgery

  • Not specified

Other

  • Recovered from prior therapy
  • No other concurrent investigational agents that would preclude study participation or increase risk to patient

    • Investigational diagnostic procedures allowed
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00054236

Locations
United States, Ohio
Case Comprehensive Cancer Center Recruiting
Cleveland, Ohio, United States, 44106-5065
Contact: Clinical Trials Office - Case Comprehensive Cancer Center     800-641-2422        
Geauga Regional Hospital Recruiting
Cleveland, Ohio, United States, 44024
Contact: Tamila Kindwall-Keller     440-285-6000        
Lake/University Ireland Cancer Center Recruiting
Cleveland, Ohio, United States, 44060
Contact: Tamila Kindwall-Keller     440-205-5755        
Mercy Cancer Center at Mercy Medical Center Recruiting
Cleveland, Ohio, United States, 44708
Contact: Tamila Kindwall-Keller     330-430-2788        
University Suburban Health Center Recruiting
Cleveland, Ohio, United States, 44121
Contact: Tamila Kindwall-Keller     216-844-3871        
UHHS Chagrin Highlands Medical Center Recruiting
Cleveland, Ohio, United States, 44122
Contact: Tamila Kindwall-Keller     216-292-1783        
UHHS Westlake Medical Center Recruiting
Cleveland, Ohio, United States, 44145
Contact: Tamila Kindwall-Keller     440-250-2001        
Southwest General Health Center Recruiting
Cleveland, Ohio, United States, 44130
Contact: Tamila Kindwall-Keller     440-816-8000        
Sponsors and Collaborators
Case Comprehensive Cancer Center
Investigators
Study Chair: Mary J. Laughlin, MD Case Comprehensive Cancer Center
  More Information

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

Study ID Numbers: CDR0000269915, CASE-CWRU-6Y01, CWRU-120132J, CASE-6Y01
Study First Received: February 5, 2003
Last Updated: December 16, 2008
ClinicalTrials.gov Identifier: NCT00054236  
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
refractory anemia with excess blasts in transformation
refractory anemia with excess blasts
adult acute myeloid leukemia in remission
childhood acute myeloid leukemia in remission
recurrent adult acute myeloid leukemia
recurrent childhood acute myeloid leukemia
adult erythroleukemia (M6a)
childhood acute erythroleukemia (M6)
adult acute minimally differentiated myeloid leukemia (M0)
childhood acute minimally differentiated myeloid leukemia (M0)
adult acute megakaryoblastic leukemia (M7)
childhood acute megakaryocytic leukemia (M7)
adult acute lymphoblastic leukemia in remission
childhood acute lymphoblastic leukemia in remission
recurrent adult acute lymphoblastic leukemia
recurrent childhood acute lymphoblastic leukemia
accelerated phase chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
previously treated myelodysplastic syndromes
refractory chronic lymphocytic leukemia
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
recurrent/refractory childhood Hodgkin lymphoma
polycythemia vera
chronic idiopathic myelofibrosis
essential thrombocythemia
refractory multiple myeloma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma

Study placed in the following topic categories:
Polycythemia
Chronic myelogenous leukemia
Refractory anemia
Hodgkin lymphoma, adult
Lymphoma, Mantle-Cell
Lymphoma, small cleaved-cell, diffuse
Di Guglielmo's syndrome
Small non-cleaved cell lymphoma
Lymphoma, large-cell, immunoblastic
Preleukemia
Hemorrhagic Disorders
Anemia, Refractory
Multiple myeloma
Leukemia, Lymphocytic, Chronic, B-Cell
Hemorrhagic thrombocythemia
Lymphoma, Large-Cell, Anaplastic
Thrombocythemia, Hemorrhagic
Acute myeloid leukemia, adult
Hodgkin Disease
Essential thrombocytosis
Chronic lymphocytic leukemia
Myelodysplastic syndromes
Lymphoma, Large B-Cell, Diffuse
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunoproliferative Disorders
Hematologic Diseases
Leukemia, B-cell, chronic
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
Blood Coagulation Disorders
Acute myelogenous leukemia

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

ClinicalTrials.gov processed this record on January 14, 2009