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Hematopoietic Stem Cell Transplantation in the Treatment of Infant Leukemia

Primary Purpose

Leukemia, Myelodysplastic Syndromes, Childhood Acute Myeloid Leukemia in Remission

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
filgrastim
busulfan
cyclosporine
fludarabine phosphate
melphalan
mycophenolate mofetil
umbilical cord blood transplantation
Sponsored by
Masonic Cancer Center, University of Minnesota
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring MDS, AML

Eligibility Criteria

undefined - 3 Years (Child)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

  • Masonic Cancer Center, University of MinnesotaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Double Unit UCB Transplantation

Single Unit UCB Transplantation

Arm Description

Patients that receive 2 units of umbilical cord blood transplantation (UCBT).

Patients that receive one unit of umbilical cord blood transplantation (only if 2 adequate size and matched units are not available).

Outcomes

Primary Outcome Measures

Incidence of Engraftment
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.

Secondary Outcome Measures

Incidence of transplant-related mortality (TRM)
defined as death due to transplant
Incidence of platelet engraftment
defined as platelet count > 50,000
Incidence of acute graft-versus-host disease (GVHD) grade II-IV and grade III-IV
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.
Incidence of chronic graft-versus-host disease (GVHD)
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.
Incidence of relapse
defined using standard criteria (bone marrow blast count and cytogenetics).
Overall survival
Alive after transplant.
Developmental Outcomes
Neuropsychological evaluation to assess baseline neurocognitive, adaptive, and behavioral functioning and presence of developmental delays
Disease-free survival
defined as patients who are alive and in hematological remission.

Full Information

First Posted
July 26, 2006
Last Updated
January 25, 2023
Sponsor
Masonic Cancer Center, University of Minnesota
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1. Study Identification

Unique Protocol Identification Number
NCT00357565
Brief Title
Hematopoietic Stem Cell Transplantation in the Treatment of Infant Leukemia
Official Title
Hematopoietic Cell Transplantation in the Treatment of Infant Leukemia and Myelodysplastic Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 2005 (Actual)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Masonic Cancer Center, University of Minnesota

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Myelodysplastic Syndromes, Childhood Acute Myeloid Leukemia in Remission, Recurrent Childhood Acute Myeloid Leukemia, Secondary Acute Myeloid Leukemia, Childhood Acute Lymphoblastic Leukemia in Remission, Previously Treated Myelodysplastic Syndrome, Secondary Myelodysplastic Syndrome, Refractory Anemia With Excess Blasts in Transformation, Refractory Anemia With Excess Blasts, Refractory Anemia, De Novo Myelodysplastic Syndrome, Childhood Myelodysplastic Syndrome
Keywords
MDS, AML

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Double Unit UCB Transplantation
Arm Type
Experimental
Arm Description
Patients that receive 2 units of umbilical cord blood transplantation (UCBT).
Arm Title
Single Unit UCB Transplantation
Arm Type
Experimental
Arm Description
Patients that receive one unit of umbilical cord blood transplantation (only if 2 adequate size and matched units are not available).
Intervention Type
Biological
Intervention Name(s)
filgrastim
Other Intervention Name(s)
G-CSF
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
busulfan
Other Intervention Name(s)
Busulfex
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
cyclosporine
Other Intervention Name(s)
CSA
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
fludarabine phosphate
Other Intervention Name(s)
Fludara
Intervention Description
Administered 25 mg/m^2 intravenous (IV) over 60 minutes on Days -4 through -2.
Intervention Type
Drug
Intervention Name(s)
melphalan
Other Intervention Name(s)
Alkeran
Intervention Description
Administered 60 mg/m^2 intravenous (IV) over 30 minutes on Days -4 through -2.
Intervention Type
Drug
Intervention Name(s)
mycophenolate mofetil
Other Intervention Name(s)
MMF
Intervention Description
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).
Intervention Type
Procedure
Intervention Name(s)
umbilical cord blood transplantation
Intervention Description
The product is infused via IV drip directly into the central line without a needle, pump or filter on Day 0.
Primary Outcome Measure Information:
Title
Incidence of Engraftment
Description
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.
Time Frame
Day 42 After Transplant
Secondary Outcome Measure Information:
Title
Incidence of transplant-related mortality (TRM)
Description
defined as death due to transplant
Time Frame
at 6 months after transplant
Title
Incidence of platelet engraftment
Description
defined as platelet count > 50,000
Time Frame
at 1 year after transplant
Title
Incidence of acute graft-versus-host disease (GVHD) grade II-IV and grade III-IV
Description
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.
Time Frame
Day 100 After Transplant
Title
Incidence of chronic graft-versus-host disease (GVHD)
Description
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.
Time Frame
1 Year After Transplant
Title
Incidence of relapse
Description
defined using standard criteria (bone marrow blast count and cytogenetics).
Time Frame
1 and 2 years after transplant
Title
Overall survival
Description
Alive after transplant.
Time Frame
at 1 and 2 years after transplant
Title
Developmental Outcomes
Description
Neuropsychological evaluation to assess baseline neurocognitive, adaptive, and behavioral functioning and presence of developmental delays
Time Frame
at 1, 2, and 5 years after transplant
Title
Disease-free survival
Description
defined as patients who are alive and in hematological remission.
Time Frame
at 1 and 2 years after transplant

10. Eligibility

Sex
All
Maximum Age & Unit of Time
3 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Christen Ebens, MD
Phone
612-624-0123
Email
ebens012@umn.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christen Ebens, MD
Organizational Affiliation
Masonic Cancer Center, University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
Masonic Cancer Center, University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christen Ebens, MD
Phone
612-624-0123
Email
ebens012@umn.edu

12. IPD Sharing Statement

Learn more about this trial

Hematopoietic Stem Cell Transplantation in the Treatment of Infant Leukemia

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