Combination Chemotherapy Followed By Donor Umbilical Cord Blood Transplant in Treating Infants With High-Risk Acute Leukemia or Myelodysplastic Syndromes - Full Text View

Sponsors and Collaborators:	Masonic Cancer Center, University of Minnesota National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00357565

Purpose

RATIONALE: Giving chemotherapy, such as busulfan, fludarabine, and melphalan, before a donor umbilical cord blood stem cell transplant helps stop the growth of abnormal or cancer cells and prepares the patient's bone marrow for the 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 cyclosporine and mycophenolate mofetil may stop this from happening.

PURPOSE: This phase II trial is studying how well combination chemotherapy followed by a donor umbilical cord blood transplant works in treating infants with high-risk acute leukemia or myelodysplastic syndromes.

Condition	Intervention	Phase
Leukemia Myelodysplastic Syndromes	Drug: busulfan Drug: cyclosporine Drug: filgrastim Drug: fludarabine phosphate Drug: melphalan Drug: mycophenolate mofetil Procedure: allogeneic hematopoietic stem cell transplantation Procedure: umbilical cord blood transplantation	Phase II

MedlinePlus related topics: Anemia Cancer Leukemia, Childhood

Drug Information available for: Filgrastim Melphalan Fludarabine Fludarabine monophosphate Cyclosporin Cyclosporine Mycophenolate Mofetil Mycophenolate mofetil hydrochloride Melphalan hydrochloride Sarcolysin Busulfan

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label
Official Title:	Hematopoietic Cell Transplantation in the Treatment of Infant Leukemia Using Double Umbilical Cord Transplantation

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

Primary Outcome Measures:

Incidence of neutrophil recovery (defined as absolute neutrophil count > 500/mm³ of donor origin) at day 42 after transplant [ Designated as safety issue: No ]

Secondary Outcome Measures:

Incidence of transplant-related mortality (TRM) at 6 months after transplant [ Designated as safety issue: No ]
Pharmacokinetics of mycophenolate mofetil and fludarabine phosphate in infants [ Designated as safety issue: No ]
Pattern of chimerism as measured by bone marrow samples on days 21 and 100 and at 6 months, 1 year, and 2 years after transplant [ Designated as safety issue: No ]
Incidence of platelet engraftment at 1 year after transplant [ Designated as safety issue: No ]
Incidence of acute graft-versus-host disease (GVHD) grade II-IV and grade III-IV at day 100 after transplant [ Designated as safety issue: No ]
Incidence of chronic GVHD at 1 year after transplant [ Designated as safety issue: No ]
Incidence of relapse at 1 and 2 years after transplant [ Designated as safety issue: No ]
Probability of survival and disease-free survival at 1 and 2 years after transplant [ Designated as safety issue: No ]
Neuropsychological testing at 1, 2, and 5 years after transplant [ Designated as safety issue: No ]

Estimated Enrollment:	20
Study Start Date:	December 2005
Estimated Primary Completion Date:	August 2013 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine the incidence of engraftment, defined as achieving donor-derived neutrophil count > 500/mm³ by day 42, in infants with high-risk acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndromes treated with a non-irradiation containing myeloablative conditioning regimen comprising busulfan, fludarabine, and melphalan followed by double umbilical cord blood transplantation (UCBT) with two partially HLA-matched units.

Secondary

Determine the incidence of transplant-related mortality (TRM) at 6 months after UCBT.
Determine the pharmacokinetics of mycophenolate mofetil and fludarabine phosphate in infants.
Evaluate the pattern of chimerism after double UCBT.
Determine the incidence of platelet engraftment at 1 year after UCBT.
Determine the incidence of acute graft-versus-host disease (GVHD) grade II-IV and grade III-IV at day 100 after UCBT.
Determine the incidence of chronic GVHD at 1 year after UCBT.
Determine the overall survival and disease-free survival at 1 and 2 years after UCBT.
Determine the incidence of relapse at 1 and 2 years after UCBT.
Evaluate the developmental outcome after UCBT.

OUTLINE: This is an open-label, nonrandomized study.

Non-irradiation containing myeloablative conditioning regimen: Patients receive busulfan IV over 2 hours 4 times daily on days -8 to -5 and fludarabine phosphate IV over 1 hour and melphalan IV over 30 minutes once daily on days -4 to -2.
Double umbilical cord blood transplantation (UCBT): Patients undergo double UCBT IV over 15-30 minutes on day 0. Beginning on day 1, patients receive filgrastim (G-CSF) IV once daily until blood counts recover.
Graft-vs-host disease prophylaxis: Patients receive cyclosporine IV over 2 hours 3 times daily and then orally twice daily beginning on day -3 and continuing until day 100 followed by a taper until day 180. Patients also receive mycophenolate mofetil IV and then orally 3 times daily beginning on day -3 and continuing until day 30 or 7 days after engraftment.

After completion of study treatment, patients are followed periodically for at least 5 years.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	up to 2 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of 1 of the following hematological malignancies:
- Acute myeloid leukemia in complete remission (CR) or early relapse (i.e., < 15% blasts in bone marrow) and meets 1 of the following criteria:
  - In first CR (CR1) with high-risk disease as evidenced by the following:
    - High-risk cytogenetics
      - t(4;11) or other MLL rearrangements
      - Chromosome 5, 7, or 19 abnormalities
      - Complex karyotype (> 5 distinct changes)
    - Required ≥ 2 courses to achieve CR
  - In second or subsequent CR
  - AML evolved from prior myelodysplastic syndromes (MDS)
- Acute lymphoblastic leukemia in CR, as defined by hematological recovery AND < 5% blasts by light microscopy within the bone marrow with a cellularity of ≥ 15%, and meets 1 of the following criteria:
  - In CR1 with high-risk disease as evidenced by the following:
    - High-risk cytogenetics
      - t(4;11) or other MLL rearrangements
      - t(9;22)
      - Hypodiploid
    - Required > 1 course to achieve CR
  - In second or subsequent CR
- MDS with < 10% blasts by a representative bone marrow aspirate morphology and meets 1 of the following criteria:
  - International Prognostic Scoring System (IPSS) score of Int-2
  - IPSS score of high risk (i.e., refractory anemia with excess blasts [RAEB], RAEB in transformation [RAEBt])
  - Refractory anemia with severe pancytopenia or high risk cytogenetics
No evidence of active extramedullary disease, including CNS leukemia
No trisomy 21
4-6/6 HLA-A, -B, -DRB1 matched unrelated donor available
- HLA-A and -B matched to antigen level resolution
- HLA-DR matched to allele level resolution
- Patients receive two partially HLA-matched units, if available
  - Double units must also be ≥ 4/6 match to each other
- No existing HLA-identical, related donor available

PATIENT CHARACTERISTICS:

Lansky play score 50-100%
Glomerular filtration rate > 60mL/min
Bilirubin ≤ 5 times upper limit of normal (ULN)
AST/ALT ≤ 5 times ULN
Alkaline phosphatase ≤ 5 times ULN
Oxygen saturation > 92%
LVEF ≥ 45%
No active infection at time of transplantation, including Aspergillus or other mold within the past 30 days
No history of HIV infection

PRIOR CONCURRENT THERAPY:

More than 6 months since prior myeloablative transplantation

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00357565

Locations

United States, Minnesota
Masonic Cancer Center at University of Minnesota	Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Clinical Trials Office - Masonic Cancer Center at University o 612-624-2620

Sponsors and Collaborators

Masonic Cancer Center, University of Minnesota

National Cancer Institute (NCI)

Investigators

Study Chair:

Michael R. Verneris, MD

Masonic Cancer Center, University of Minnesota

More Information

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

Responsible Party:	Masonic Cancer Center at University of Minnesota ( Michael R. Verneris )
Study ID Numbers:	CDR0000486954, UMN-2005LS075, UMN-MT2005-25, UMN-0511M77206
Study First Received:	July 26, 2006
Last Updated:	October 24, 2008
ClinicalTrials.gov Identifier:	NCT00357565
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

childhood acute myeloid leukemia in remission
recurrent childhood acute myeloid leukemia
secondary acute myeloid leukemia
childhood acute lymphoblastic leukemia in remission
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes

refractory anemia with excess blasts in transformation
refractory anemia with excess blasts
refractory anemia
de novo myelodysplastic syndromes
childhood myelodysplastic syndromes

Study placed in the following topic categories:

Melphalan
Leukemia, Lymphoid
Cyclosporine
Precancerous Conditions
Clotrimazole
Refractory anemia
Miconazole
Leukemia, Myeloid, Acute
Cyclosporins
Leukemia
Preleukemia
Anemia, Refractory
Mycophenolate mofetil
Neoplasm Metastasis
Acute myelocytic leukemia

Myelodysplastic syndromes
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Hematologic Diseases
Myelodysplastic Syndromes
Myelodysplasia
Tioconazole
Anemia
Acute myelogenous leukemia
Leukemia, Myeloid
Fludarabine monophosphate
Recurrence
Busulfan
Anemia, Refractory, with Excess of Blasts
Fludarabine
Bone Marrow Diseases

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Neoplasms by Histologic Type
Disease
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Enzyme Inhibitors

Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Pathologic Processes
Therapeutic Uses
Syndrome
Antifungal Agents
Antirheumatic Agents
Dermatologic Agents

ClinicalTrials.gov processed this record on January 16, 2009