Hematopoietic Stem Cell Transplantation in the Treatment of Infant Leukemia

NCT00357565 | Completed Phase 2 Results DMC

• 3 other identifiers: 2005LS075UMN-MT2005-25UMN-0511M77206
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Day 42 After Transplant

Secondary Outcomes (7)

• Incidence of Transplant-related Mortality (TRM)

  at 6 months after transplant

• Incidence of Platelet Engraftment

  at 1 year after transplant

• Incidence of Acute Graft-versus-host Disease (GVHD) Grade II-IV and Grade III-IV

  Day 100 After Transplant

• Incidence of Chronic Graft-versus-host Disease (GVHD)

  1 Year After Transplant

• Incidence of Relapse

  1 and 2 years after transplant

Study Arms (2)

Double Unit UCB Transplantation

EXPERIMENTAL

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

Biological: filgrastim; Drug: busulfan; Drug: cyclosporine; Drug: fludarabine phosphate; Drug: melphalan; Drug: mycophenolate mofetil; Procedure: umbilical cord blood transplantation

Single Unit UCB Transplantation

EXPERIMENTAL

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

Biological: filgrastim; Drug: busulfan; Drug: cyclosporine; Drug: fludarabine phosphate; Drug: melphalan; Drug: mycophenolate mofetil; Procedure: umbilical cord blood transplantation

Interventions

filgrastim BIOLOGICAL

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.

Also known as: G-CSF

Double Unit UCB Transplantation; Single Unit UCB Transplantation

busulfan DRUG

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.

Also known as: Busulfex

Double Unit UCB Transplantation; Single Unit UCB Transplantation

cyclosporine DRUG

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.

Also known as: CSA

Double Unit UCB Transplantation; Single Unit UCB Transplantation

fludarabine phosphate DRUG

Administered 25 mg/m\^2 intravenous (IV) over 60 minutes on Days -4 through -2.

Also known as: Fludara

Double Unit UCB Transplantation; Single Unit UCB Transplantation

melphalan DRUG

Administered 60 mg/m\^2 intravenous (IV) over 30 minutes on Days -4 through -2.

Also known as: Alkeran

Double Unit UCB Transplantation; Single Unit UCB Transplantation

mycophenolate mofetil DRUG

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).

Also known as: MMF

Double Unit UCB Transplantation; Single Unit UCB Transplantation

umbilical cord blood transplantation PROCEDURE

The product is infused via IV drip directly into the central line without a needle, pump or filter on Day 0.

Double Unit UCB Transplantation; Single Unit UCB Transplantation

Eligibility Criteria

• Age: Up to 3 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Matched sibling donor (HLA 8/8), if available, or a unrelated partially HLA matched single unit based on the following priority:
• st priority: 4/6 matched unit, cell dose \>5 x 10-7 nucleated cells/kg
• nd priority: 5/6 matched unit, cell dose \> 4 x 10-7 nucleated cells/kg
• rd 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%

You may not qualify if:

• 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).

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes; Anemia, Refractory, with Excess of Blasts; Anemia, Refractory

Interventions

Filgrastim; Granulocyte Colony-Stimulating Factor; Busulfan; Cyclosporine; fludarabine phosphate; Melphalan; Mycophenolic Acid; Cord Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Anemia

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: Christen Ebens, MD, MPH
• Organization: Masonic Cancer Center

ebens012@umn.edu

(612) 626-2961

Study Officials

• Christen Ebens, MD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2006
• First Posted: July 27, 2006
• Study Start: November 1, 2005
• Primary Completion: June 1, 2024
• Study Completion: March 11, 2025
• Last Updated: August 26, 2025
• Results First Posted: August 26, 2025

Record last verified: 2025-08

Locations

US (1)