Umbilical Cord Blood Stem Cell Transplant in Treating Patients With Hematologic Cancer or Other Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Barbara Ann Karmanos Cancer Institute
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Voravit Ratanatharathorn, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier:
NCT00423826
First received: January 16, 2007
Last updated: May 15, 2014
Last verified: May 2014
  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
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Precancerous Condition
Secondary Myelofibrosis
Drug: Busulfan
Drug: Cytarabine
Drug: Fludarabine phosphate
Drug: mycophenolate mofetil
Drug: tacrolimus
Procedure: allogeneic hematopoietic stem cell transplantation
Procedure: umbilical cord blood transplantation
Radiation: total-body irradiation

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of Double Cord Blood Stem Cell Transplantation in Patients With Hematologic Malignancies

Resource links provided by NLM:

Genetic and Rare Diseases Information Center resources: Leukemia, Myeloid Chronic Myeloid Leukemia Myelodysplastic Syndromes Lymphosarcoma Lymphoma, Small Cleaved-cell, Diffuse Acute Lymphoblastic Leukemia Multiple Myeloma Hodgkin Lymphoma Waldenstrom Macroglobulinemia Acute Myelocytic Leukemia Acute Non Lymphoblastic Leukemia Acute Myeloid Leukemia, Adult Follicular Lymphoma Hodgkin Lymphoma, Childhood B-cell Lymphomas Myelofibrosis Burkitt Lymphoma Lymphoma, Large-cell Lymphomatoid Granulomatosis Lymphoma, Large-cell, Immunoblastic Plasmablastic Lymphoma Lymphoblastic Lymphoma Small Non-cleaved Cell Lymphoma Chronic Lymphocytic Leukemia Leukemia, B-cell, Chronic Acute Lymphoblastic Leukemia, Childhood Acute Myeloid Leukemia, Childhood Monoclonal Gammopathy of Undetermined Significance Acute Promyelocytic Leukemia Mantle Cell Lymphoma AL Amyloidosis Acute Erythroblastic Leukemia Acute Erythroid Leukemia Di Guglielmo's Syndrome Acute Megakaryoblastic Leukemia Acute Monoblastic Leukemia Acute Myelomonocytic Leukemia Acute Myeloblastic Leukemia Without Maturation Acute Myeloblastic Leukemia With Maturation Anaplastic Plasmacytoma Chronic Myeloproliferative Disorders
U.S. FDA Resources

Further study details as provided by Barbara Ann Karmanos Cancer Institute:

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

Secondary Outcome Measures:
  • Mortality [ Time Frame: Within 100 days post transplantation ] [ Designated as safety issue: No ]
  • Rate of graft failure [ Time Frame: Within 23 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 29
Study Start Date: January 2007
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Busulfan Cytarabine Fludarabine Tacrolimus Mycophenolate
Busulfan 3mg/kg-3hrs; Ara-C 30mg/M2; Fludarabine phosphate:25mg/M2/day; Tacrolimus:0.015mg/kg every 12 hrs
Drug: Busulfan
3 mg/kg intravenously over 3 hours
Other Names:
  • Busulfex®
  • Myleran®
Drug: Cytarabine
Patients with previous history of CNS involvement will receive pre-transplant intrathecal Cytarabine (Ara-C) (30 mg/M2) therapy.
Other Names:
  • DepoCyt(TM)
  • Liposomal Ara-C
Drug: Fludarabine phosphate
25 mg/M2/day IV
Other Name: Fludara
Drug: mycophenolate mofetil
Orally at the dose of 1 gm every 8 hours.
Other Name: Cellcept
Drug: tacrolimus
0.015 mg/kg IV every 12 hours by continuous infusion.
Other Names:
  • Advagraf
  • Prograf
  • Protopic
Procedure: allogeneic hematopoietic stem cell transplantation
10 days post drug intervention
Procedure: umbilical cord blood transplantation
10 days post drug intervention
Radiation: total-body irradiation
10 days post drug intervention

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
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: NCT00423826

Locations
United States, Michigan
Barbara Ann Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201-1379
Contact: Voravit Ratanatharathorn, MD    313-576-8755    ratanath@karmanos.org   
Sub-Investigator: Muneer Abidi, M.D.         
Sub-Investigator: Lois Ayash, M.D.         
Sub-Investigator: Ronald Chu, M.D.         
Sub-Investigator: Abhinav Deol         
Sub-Investigator: Yaddanapudi Ravindranath         
Sub-Investigator: Sureyya Savasan         
Sub-Investigator: Joseph Uberti, M.D.         
Sponsors and Collaborators
Barbara Ann Karmanos Cancer Institute
Investigators
Study Chair: Voravit Ratanatharathorn, MD Barbara Ann Karmanos Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Voravit Ratanatharathorn, Principal Investigator, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier: NCT00423826     History of Changes
Other Study ID Numbers: CDR0000518230, P30CA022453, WSU-2006-059, WSU-112506MP2F
Study First Received: January 16, 2007
Last Updated: May 15, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Barbara Ann Karmanos Cancer Institute:
extramedullary plasmacytoma
isolated plasmacytoma of bone
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)

Additional relevant MeSH terms:
Plasmacytoma
Primary Myelofibrosis
Neoplasms
Leukemia
Lymphoma
Multiple Myeloma
Neoplasms, Plasma Cell
Myelodysplastic Syndromes
Preleukemia
Precancerous Conditions
Lymphoma, Large-Cell, Immunoblastic
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hemorrhagic Disorders
Lymphoma, Non-Hodgkin
Busulfan
Cytarabine
Mycophenolate mofetil
Fludarabine phosphate

ClinicalTrials.gov processed this record on July 31, 2014