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Umbilical Cord 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), December 2008
Sponsors and Collaborators: Barbara Ann Karmanos Cancer Institute
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00423826
  Purpose

RATIONALE: Giving low doses of chemotherapy and total-body irradiation before a donor umbilical cord blood stem cell transplant helps stop the growth of cancer or abnormal cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer or abnormal cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus and mycophenolate mofetil before the transplant may stop this from happening.

PURPOSE: This clinical trial is studying how well umbilical cord blood stem cell transplant works in treating patients with hematologic cancer or other disease.


Condition Intervention
Cancer-Related Problem/Condition
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Precancerous/Nonmalignant Condition
Drug: busulfan
Drug: cytarabine
Drug: fludarabine phosphate
Drug: mycophenolate mofetil
Drug: tacrolimus
Procedure: allogeneic hematopoietic stem cell transplantation
Procedure: total-body irradiation
Procedure: umbilical cord blood transplantation

Genetics Home Reference related topics: aceruloplasminemia hemophilia
MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood Lymphoma Multiple Myeloma
Drug Information available for: Cytarabine Cytarabine hydrochloride Fludarabine Fludarabine monophosphate Tacrolimus Mycophenolate Mofetil Mycophenolate mofetil hydrochloride Tacrolimus anhydrous Busulfan
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment
Official Title: A Pilot Study of Double Cord Blood Stem Cell Transplantation in Patients With Hematologic Malignancies

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

Primary Outcome Measures:
  • Engraftment at 60 days post transplantation [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Mortality within 100 days post transplantation [ Designated as safety issue: No ]
  • Rate of graft failure [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: January 2007
Estimated Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Determine the efficacy of double umbilical cord blood stem cell transplantation using a conditioning regimen comprising lower doses of busulfan and fludarabine phosphate and low-dose total body irradiation, in terms of stem cell engraftment at 60 days post transplantation, in patients with hematologic cancer or other diseases.
  • Determine the merits of conducting a larger, comparative study of this regimen.

Secondary

  • Determine mortality within 100 days of transplantation in these patients.

OUTLINE: This is a pilot study.

  • Reduced-intensity conditioning regimen: Patients receive busulfan IV over 3 hours on days -9 to -8 and fludarabine phosphate IV on days -7 to -3. Patients then undergo low-dose total body irradiation on day 0.
  • Graft-versus-host disease prophylaxis: Patients receive tacrolimus IV twice daily and mycophenolate orally or IV three times daily beginning on day -3.
  • CNS prophylaxis and/or treatment: Patients with a history of CNS involvement receive prophylactic cytarabine (Ara-C) intrathecally (IT) prior to transplant. Patients also undergo lumbar puncture (LP) to test for active CNS disease. Patients with cerebrospinal fluid positive for leukemia receive Ara-C IT every 2-3 days until a repeat LP shows no remaining leukemic cells. Three days after the last LP and after one final dose of Ara-C, patients begin the conditioning regimen.
  • Double umbilical cord blood (UCB) donor stem cell transplantation (SCT): Patients undergo double UCB donor SCT on day 0.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   up to 69 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed diagnosis of 1 of the following:

    • Acute myeloid leukemia meeting the following criteria:

      • M0-M7 histologic subtypes by French-American-British classification
      • Previously treated disease
      • Meets 1 of the following criteria:

        • Persistent disease as evidenced by 5-30% persistent blasts in bone marrow after induction or salvage therapy
        • In second or subsequent complete remission (CR)
        • In first CR with 1 of the following high-risk features:

          • Philadelphia chromosome present
          • Noncore-binding factor type of chromosomal abnormalities
    • Myelodysplastic syndromes with 1 of the following International Prognostic Scoring System (IPSS) scores:

      • Intermediate-1
      • Intermediate-2
      • High-risk score with transfusion dependence
    • Chronic myelogenous leukemia meeting 1 of the following criteria:

      • In accelerated or blastic phase
      • Failed prior imatinib mesylate therapy
    • Acute lymphoblastic leukemia meeting 1 of the following criteria:

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

        • Philadelphia chromosome present
        • Translocation t(4;11) present
        • WBC > 30,000/mm³ (adult patients)
        • More than 4 weeks from initiation of treatment was required to achieve CR (adult patients)
        • DNA index of near haploid (N=23 chromosomes) (pediatric patients)
      • In second or subsequent CR
      • Persistent disease as evidenced by 5-20% persistent blasts in bone marrow after induction or salvage therapy
    • Hodgkin's or non-Hodgkin's lymphoma meeting the following criteria:

      • Recurrent or refractory disease
      • Tumor ≤ 5 cm in diameter
    • Myeloma or plasma cell neoplasm meeting 1 of the following staging criteria:

      • Stage III at presentation
      • Stage I-II at presentation

        • Not responding OR progressed after first-line therapy
    • Chronic lymphocytic leukemia or Waldenstrom's macroglobulinemia with refractory or progressive disease after first-line therapy
  • No 5-6/6 HLA-matched related or 7-8/8 HLA-matched unrelated marrow or peripheral blood stem cell donor available
  • No single 4-6/6 HLA-A, -B, or -DRB1-matched umbilical cord blood unit ≥ 3.5 x 10^7 nucleated cells/kg available

PATIENT CHARACTERISTICS:

  • ECOG performance status (PS) 0-2 OR Karnofsky or Lansky PS 70-100%
  • Not pregnant
  • Fertile patients must use effective contraception prior to and during study participation
  • HIV negative
  • Bilirubin < 3.0 mg/dL
  • AST and ALT ≤ 3 times upper limit of normal
  • Creatinine < 2.0 mg/dL OR creatinine clearance > 50 mL/min
  • Cardiac ejection fraction > 50% by echocardiogram OR shortening fraction > 27%
  • No uncontrolled symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia
  • FEV_1 > 50% of normal
  • Forced vital capacity > 50% of normal
  • DLCO normal
  • Oxygen saturation > 92% on room air (for patients < 5 years of age)
  • No history of allergic reactions attributed to compounds of similar chemical or biological composition to busulfan and fludarabine phosphate
  • No ongoing or active infection
  • No psychiatric illness or social situation that would preclude study compliance
  • No other uncontrolled illness

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • At least 4 weeks since prior and no concurrent surgery
  • At least 4 weeks since prior and no other concurrent investigational or commercial agents or therapies for the malignancy, including chemotherapy, biologic therapy, or radiotherapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00423826

Locations
United States, Michigan
Barbara Ann Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201-1379
Contact: Roland L. Chu, MD     313-745-5515     rchu@med.wayne.edu    
Sponsors and Collaborators
Barbara Ann Karmanos Cancer Institute
Investigators
Study Chair: Roland L. Chu, MD Barbara Ann Karmanos Cancer Institute
  More Information

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

Study ID Numbers: CDR0000518230, WSU-2006-059, WSU-112506MP2F
Study First Received: January 16, 2007
Last Updated: December 9, 2008
ClinicalTrials.gov Identifier: NCT00423826  
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
childhood chronic myelogenous leukemia
relapsing chronic myelogenous leukemia
adult acute lymphoblastic leukemia in remission
recurrent adult acute lymphoblastic leukemia
childhood acute lymphoblastic leukemia in remission
recurrent childhood acute lymphoblastic leukemia
adult acute myeloid leukemia in remission
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)
recurrent adult acute myeloid leukemia
adult acute minimally differentiated myeloid leukemia (M0)
adult acute myeloblastic leukemia without maturation (M1)
adult acute myeloblastic leukemia with maturation (M2)
adult acute promyelocytic leukemia (M3)
adult acute myelomonocytic leukemia (M4)
adult acute monoblastic leukemia (M5a)
adult acute monocytic leukemia (M5b)
adult erythroleukemia (M6a)
adult pure erythroid leukemia (M6b)
adult acute megakaryoblastic leukemia (M7)
childhood acute myeloblastic leukemia without maturation (M1)
childhood acute myeloblastic leukemia with maturation (M2)
childhood acute promyelocytic leukemia (M3)
childhood acute myelomonocytic leukemia (M4)
childhood acute monoblastic leukemia (M5a)

Study placed in the following topic categories:
Blast Crisis
Chronic myelogenous leukemia
Hodgkin lymphoma, adult
Lymphoma, Mantle-Cell
Lymphoma, small cleaved-cell, diffuse
Tacrolimus
Di Guglielmo's syndrome
Small non-cleaved cell lymphoma
Lymphoma, large-cell, immunoblastic
Lymphomatoid granulomatosis
Preleukemia
Hemorrhagic Disorders
Multiple myeloma
Leukemia, Lymphocytic, Chronic, B-Cell
Mycophenolate mofetil
Leukemia, Promyelocytic, Acute
Neoplasm Metastasis
Acute myeloid leukemia, adult
Hodgkin Disease
Chronic lymphocytic leukemia
Myelodysplastic syndromes
Lymphoma, Large B-Cell, Diffuse
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunoproliferative Disorders
Hematologic Diseases
Leukemia, B-cell, chronic
Blood Coagulation Disorders
Acute promyelocytic leukemia
Acute myelogenous leukemia
Leukemia, Myeloid

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

ClinicalTrials.gov processed this record on January 14, 2009