Overview

This trial is active, not recruiting.

Conditions acute myelogenous leukemia, myelodysplastic syndrome, juvenile myelomonocytic leukemia
Treatments fludarabine, busulfan, graft-versus-host disease (gvhd) prophylaxis, gemtuzumab ozogamicin, anti-thymocyte globulin, isotretinoin
Phase phase 1
Sponsor Columbia University
Start date January 2005
End date April 2017
Trial size 18 participants
Trial identifier NCT01020539, AAAA6378, CHNY-504

Summary

Allogeneic stem cell transplantation (AlloSCT) followed by targeted immune therapy Gemtuzumab Ozogamicin patients with acute myeloid leukemia (AML)/juvenile myelomonocytic leukemia (JMML)/myelodysplastic syndromes (MDS) will be safe and well tolerated.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Stem Cell Transplant will be performed using the matched family donor SCT.
fludarabine Fludara®
Conditioning Regimen
busulfan Busulfex®
Conditioning Regimen
graft-versus-host disease (gvhd) prophylaxis
Can be FK506 (Tacrolimus/Prograf®), mycophenolate mofetil ((MMF)/Cellcept®), or methotrexate (MTX, amethopterin)
gemtuzumab ozogamicin Mylotarg®
Dose Escalation
(Experimental)
Stem Cell Transplant will be performed using Unrelated Donor SCT.
anti-thymocyte globulin Thymoglobulin®
Unrelated Donors only
isotretinoin Accutane®
JMML patients only

Primary Outcomes

Measure
Maximal tolerated and/or biologically active dose of Gemtuzumab Ozogamicin (GO)
time frame: Up to 2 years

Secondary Outcomes

Measure
Change of minimal residual disease
time frame: Day 60, Day 100, Day 180, 1 year, 2 years
Incidence of minor histocompatibility antigen (MHA) expression on acute myeloid leukemia (AML) tissue
time frame: Up to 2 years
Degree of mixed/complete donor chimerism
time frame: Up to 2 years
Event free survival (EFS) rate
time frame: Up to 2 years
Overall survival (OS) rate
time frame: Up to 2 years

Eligibility Criteria

Male or female participants from 1 month up to 30 years old.

Inclusion Criteria: Disease Status - AML 1st CR with a matched family donor (excluding Downs Syndrome, APL, poor cytogenetics [12p, 5q, -7 and FLT3 mutations or duplication t(9;11) and others]) and patients consented to and registered on an upfront AML COG study with a matched family donor) - AML 1st CR [excluding Downs Syndrome, APL, and chromosome translocation (8;21) or inversion (16) or poor cytogenetics (12p, 5q, -7, FLT3 mutation or duplication t(9;11) and others)] with unrelated donor - AML 2nd CR - Myelodysplastic Syndrome (MDS) and ≤ 5% bone marrow myeloblasts at diagnosis (de novo patients only) - Juvenile Myelomonocytic Leukemia (JMML) and ≤ 5% bone marrow myeloblasts at diagnosis In regards to disease immunophenotype, disease must express a minimum of ≥10% CD33 positivity for patients with AML Organ Function: Patients must have adequate organ function as defined below: Adequate renal function defined as: - Serum creatinine < 1.5 x normal, or - Creatinine clearance or radioisotope glomerular filtration rate (GFR) 40 ml/min/m2 or > 60 ml/min/1.73 m2 or an equivalent GFR as determined by the institutional normal range Adequate liver function defined as total bilirubin 2.0 x upper limit of normal (ULN), or serum glutamic-oxaloacetic transaminase (SGOT)(aspartate aminotransferase (AST)) or serum glutamic-pyruvic transaminase (SGPT)(alanine aminotransferase (ALT)) < 5.0 xULN Adequate cardiac function defined as: - Shortening fraction of ≥ 25% by echocardiogram, or - Ejection fraction of ≥ 45% by radionuclide angiogram or echocardiogram Adequate pulmonary function defined as: - Diffusion capacity of the lung for carbon monoxide (DLCO) ≥ 40% by pulmonary function tests (PFT) (Uncorrected) - For children who are uncooperative, no evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% on room air Exclusion Criteria: - Patients with active central nervous system (CNS) AML/JMML disease at time of preparative regimen - Secondary MDS - Poor cytogenetics (12p, 5q, -7, FLT3 mutation or duplication) - Female patients who are pregnant (positive human chorionic gonadotropin(hCG)) - Karnofsky <70% or Lansky <50% if 10 years or less - Age >30 years - Seropositive for Human Immunodeficiency Virus (HIV) - Patients consented to and registered on an upfront Children's Oncology Group (COG) AML study with a matched family donor

Additional Information

Official title Allogeneic Stem Cell Transplantation Followed By Targeted Immune Therapy In Average Risk Acute Myelogenous Leukemia/Myelodysplastic Syndrome/Juvenile Myelomonocytic Leukemia (AML/MDS/JMML)
Principal investigator Monica Bhatia, MD
Description Gemtuzumab Ozogamicin (CMA-676) is a chemotherapeutic agent consisting of a recombinant humanized anti-CD33 antibody conjugated with calicheamicin, a highly potent cytotoxic antitumor antibiotic. The antibody portion of Gemtuzumab binds specifically to the CD33 antigen, a sialic acid-dependent adhesion protein expressed on the surface of leukemic blasts, normal and leukemic myeloid colony-forming cells, including leukemic clonogenic precursors, but excluding pluripotent hematopoietic stem cells and nonhematopoietic cells. This results in formation of a complex that is internalized, upon which the calicheamicin derivative is released within the lysosomes of the myeloid cell. The free calicheamicin derivative then binds to deoxyribonucleic acid (DNA), resulting in DNA double strand breaks and consequential cell death. Over 80% of AML patients possess myeloid blast cells with CD33 surface antigen expression.
Trial information was received from ClinicalTrials.gov and was last updated in January 2016.
Information provided to ClinicalTrials.gov by Columbia University.