- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00357565
Hematopoietic Stem Cell Transplantation in the Treatment of Infant Leukemia
Hematopoietic Cell Transplantation in the Treatment of Infant Leukemia and Myelodysplastic Syndrome
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.
Study Overview
Status
Conditions
- Myelodysplastic Syndromes
- Leukemia
- Previously Treated Myelodysplastic Syndrome
- Secondary Acute Myeloid Leukemia
- Childhood Acute Myeloid Leukemia in Remission
- Childhood Acute Lymphoblastic Leukemia in Remission
- Recurrent Childhood Acute Myeloid Leukemia
- Secondary Myelodysplastic Syndrome
- Refractory Anemia
- Refractory Anemia With Excess Blasts
- Refractory Anemia With Excess Blasts in Transformation
- Childhood Myelodysplastic Syndrome
- De Novo Myelodysplastic Syndrome
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 Objectives
- Determine the incidence of transplant-related mortality (TRM) at 6 months after UCBT
- Evaluate 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
- Evaluate the developmental outcome after UCBT
Transplant Related Objectives
- Determine the incidence of chronic GVHD at 1 year after UCBT
- Determine the survival and disease free survival at 1 and 2 years after UCBT
- Determine the incidence relapse at 1 and 2 years after UCBT
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Christen Ebens, MD
- Phone Number: 612-624-0123
- Email: ebens012@umn.edu
Study Locations
-
-
Minnesota
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Minneapolis, Minnesota, United States, 55455
- Recruiting
- Masonic Cancer Center, University of Minnesota
-
Contact:
- Christen Ebens, MD
- Phone Number: 612-624-0123
- Email: ebens012@umn.edu
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
Matched sibling donor (HLA 8/8), if available, or a unrelated partially HLA matched single unit based on the following priority:
- 1st priority: 4/6 matched unit, cell dose >5 x 10-7 nucleated cells/kg
- 2nd priority: 5/6 matched unit, cell dose > 4 x 10-7 nucleated cells/kg
- 3rd priority: 6/6 matched unit, cell dose > 3 x 10-7 nucleated cells/kg
Patients aged ≤ 3 years at diagnosis (not age of transplant) with hematological malignancy as detailed below:
Acute myeloid leukemia: high risk CR1 as evidenced by:
- High risk cytogenetics t(4;11) or other MLL rearrangements; chromosome 5, 7, or 19 abnormalities; complex karyotype (>5 distinct changes); ≥ 2 cycles to obtain complete response (CR); CR2 or higher; Preceding myelodysplastic syndrome (MDS); All patients must be in CR or early relapse (i.e., <15% blasts in BM).
- Acute lymphocytic leukemia: high risk CR1 as evidenced by: High-risk cytogenetic: t(4;11) or other MLL rearrangements; hypodiploid; t(9;22); >1 cycle to obtain CR; CR2 or higher; All patients must be in CR as defined by hematological recovery, AND <5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%.
- Myelodysplasia (MDS) IPSS Int-2 or High risk (i.e. RAEB, RAEBt) or refractory anemia with severe pancytopenia or high risk cytogenetics. Blasts must be < 10% by a representative bone marrow aspirate morphology.
- Persistent or rising minimal residual disease (MRD) after standard chemotherapy regimens: Patients with evidence of minimal residual disease at the completion of therapy or evidence of rising MRD while on therapy. MRD will be defined by either flow cytometry (>0.1% residual cells in the blast gate with immune phenotype of original leukemic clone), by molecular techniques (PCR or FISH) or conventional cytogenetics (g-banding).
- New Leukemia Subtypes: A major effort in the field of pediatric hematology is to identify patients who are of high risk for treatment failure so that patients can be appropriately stratified to either more (or less) intensive therapy. This effort is continually ongoing and retrospective studies identify new disease features or characteristics that are associated with treatment outcomes. Therefore, if new high risk features are identified after the writing of this protocol, patients can be enrolled with the approval of two members of the study committee.
Recipients must have a Lansky score ≥ 50% and have acceptable organ function defined as:
- Renal: glomerial filtration rate > 60ml/min/1.73m^2
- Hepatic: bilirubin, AST/ALT, ALP < 5 x upper limit of normal,
- Pulmonary function: oxygen saturation >92%
- Cardiac: left ventricular ejection fraction > 45%.
- Voluntary written informed consent before performance of any study-related procedure not part of normal medical care.
Exclusion Criteria:
- Active infection at time of transplantation (including active infection with Aspergillus or other mold within 30 days).
- History of HIV infection or known positive serology
- Myeloablative transplant within the last 6 months.
- Evidence of active extramedullary disease (including central nervous system leukemia).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Double Unit UCB Transplantation
Patients that receive 2 units of umbilical cord blood transplantation (UCBT).
|
All patients will receive G-CSF 5 mcg/kg/day intravenous (IV) (dose rounded to vial size) based on the actual body weight IV beginning on day +1 after umbilical cord blood (UCB) infusion.
G-CSF will be administered daily until the absolute neutrophil count (ANC) exceeds 2.5 x 10^9/L for three consecutive days and then discontinued.
If the ANC decreases to <1.0 x 10^9/L, G-CSF will be reinstituted.
Other Names:
Administered 1.1 mg/kg if <12 kg intravenous (IV) every 6 hours (0.8 mg/kg if >12 kg IV every 6 hours on Days -8 through -5.
Other Names:
Patients will receive cyclosporine (CSA) therapy beginning on day -3 maintaining a level of >200 ng/mL.
For children < 40 kg the initial dose will be 2.5 mg/kg intravenous (IV) over 2 hours every 8 hours.
Other Names:
Administered 25 mg/m^2 intravenous (IV) over 60 minutes on Days -4 through -2.
Other Names:
Administered 60 mg/m^2 intravenous (IV) over 30 minutes on Days -4 through -2.
Other Names:
All patients will begin mycophenolate mofetil (MMF) on day -3.
Patients <45 kilograms will receive MMF at the dose of 15 mg/kg/dose every 8 hours (max dose 1gm/dose) orally or intravenously (PO or IV).
Other Names:
The product is infused via IV drip directly into the central line without a needle, pump or filter on Day 0.
|
Experimental: Single Unit UCB Transplantation
Patients that receive one unit of umbilical cord blood transplantation (only if 2 adequate size and matched units are not available).
|
All patients will receive G-CSF 5 mcg/kg/day intravenous (IV) (dose rounded to vial size) based on the actual body weight IV beginning on day +1 after umbilical cord blood (UCB) infusion.
G-CSF will be administered daily until the absolute neutrophil count (ANC) exceeds 2.5 x 10^9/L for three consecutive days and then discontinued.
If the ANC decreases to <1.0 x 10^9/L, G-CSF will be reinstituted.
Other Names:
Administered 1.1 mg/kg if <12 kg intravenous (IV) every 6 hours (0.8 mg/kg if >12 kg IV every 6 hours on Days -8 through -5.
Other Names:
Patients will receive cyclosporine (CSA) therapy beginning on day -3 maintaining a level of >200 ng/mL.
For children < 40 kg the initial dose will be 2.5 mg/kg intravenous (IV) over 2 hours every 8 hours.
Other Names:
Administered 25 mg/m^2 intravenous (IV) over 60 minutes on Days -4 through -2.
Other Names:
Administered 60 mg/m^2 intravenous (IV) over 30 minutes on Days -4 through -2.
Other Names:
All patients will begin mycophenolate mofetil (MMF) on day -3.
Patients <45 kilograms will receive MMF at the dose of 15 mg/kg/dose every 8 hours (max dose 1gm/dose) orally or intravenously (PO or IV).
Other Names:
The product is infused via IV drip directly into the central line without a needle, pump or filter on Day 0.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of Engraftment
Time Frame: Day 42 After Transplant
|
Defined as achieving donor derived neutrophil count >500/uL by day 42 in young children with leukemia or myelodysplastic syndrome undergoing a partially matched single unit umbilical cord blood transplant (UCBT) after a myeloablative preparative regimen consisting of busulfan, melphalan and fludarabine.
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Day 42 After Transplant
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of transplant-related mortality (TRM)
Time Frame: at 6 months after transplant
|
defined as death due to transplant
|
at 6 months after transplant
|
Incidence of platelet engraftment
Time Frame: at 1 year after transplant
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defined as platelet count > 50,000
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at 1 year after transplant
|
Incidence of acute graft-versus-host disease (GVHD) grade II-IV and grade III-IV
Time Frame: Day 100 After Transplant
|
Graft-versus-host disease (GVHD) is a common complication of allogeneic bone marrow transplantation in which functional immune cells in the transplanted marrow recognize the recipient as "foreign" and mount an immunologic attack.
|
Day 100 After Transplant
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Incidence of chronic graft-versus-host disease (GVHD)
Time Frame: 1 Year After Transplant
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Graft-versus-host disease (GVHD) is a common complication of allogeneic bone marrow transplantation in which functional immune cells in the transplanted marrow recognize the recipient as "foreign" and mount an immunologic attack.
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1 Year After Transplant
|
Incidence of relapse
Time Frame: 1 and 2 years after transplant
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defined using standard criteria (bone marrow blast count and cytogenetics).
|
1 and 2 years after transplant
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Overall survival
Time Frame: at 1 and 2 years after transplant
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Alive after transplant.
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at 1 and 2 years after transplant
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Developmental Outcomes
Time Frame: at 1, 2, and 5 years after transplant
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Neuropsychological evaluation to assess baseline neurocognitive, adaptive, and behavioral functioning and presence of developmental delays
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at 1, 2, and 5 years after transplant
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Disease-free survival
Time Frame: at 1 and 2 years after transplant
|
defined as patients who are alive and in hematological remission.
|
at 1 and 2 years after transplant
|
Collaborators and Investigators
Investigators
- Principal Investigator: Christen Ebens, MD, Masonic Cancer Center, University of Minnesota
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Disease
- Bone Marrow Diseases
- Hematologic Diseases
- Neoplastic Processes
- Precancerous Conditions
- Leukemia, Lymphoid
- Syndrome
- Myelodysplastic Syndromes
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Neoplasm Metastasis
- Preleukemia
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Anemia
- Anemia, Refractory, with Excess of Blasts
- Anemia, Refractory
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Dermatologic Agents
- Anti-Bacterial Agents
- Antibiotics, Antineoplastic
- Antifungal Agents
- Antitubercular Agents
- Antibiotics, Antitubercular
- Calcineurin Inhibitors
- Melphalan
- Fludarabine
- Fludarabine phosphate
- Mycophenolic Acid
- Busulfan
- Cyclosporine
- Cyclosporins
Other Study ID Numbers
- 2005LS075
- UMN-MT2005-25 (Other Identifier: Blood and Marrow Transplantation Program)
- UMN-0511M77206 (Other Identifier: IRB, University of Minnesota)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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