Clinical trial NCT01020539: Allogeneic Stem Cell Transplantation Followed By Targeted Immune Therapy In Average Risk Leukemia
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Myelogenous Leukemia
Myelodysplastic Syndrome
Juvenile Myelomonocytic Leukemia
Keywords: Allogeneic Stem Cell Transplantation
Targeted Immune Therapy
Acute Myelogenous Leukemia
Myelodysplastic Syndrome
Juvenile Myelomonocytic Leukemia
AML
MDS
JMML
Lead sponsor: Columbia University
Sponsor class: OTHER
First posted: 2009-11-25
Enrollment: 18
Sex: ALL
Minimum age (years): 1
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: Inclusion Criteria:

Disease Status

* AML 1st complete remission (CR) with a matched family donor (excluding Downs Syndrome, acute promyelocytic leukaemia (APL), poor cytogenetics (12p, 5q, -7 and FMS-like tyrosine kinase 3 (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% Cell Differential 33 (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 x ULN

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

Primary outcomes:
measure: Maximal tolerated and/or biologically active dose of Gemtuzumab Ozogamicin (GO)
timeFrame: Up to 2 years
Secondary outcomes:
measure: Change of minimal residual disease
timeFrame: Day 60, Day 100, Day 180, 1 year, 2 years
measure: Incidence of minor histocompatibility antigen (MHA) expression on acute myeloid leukemia (AML) tissue
timeFrame: Up to 2 years
measure: Degree of mixed/complete donor chimerism
timeFrame: Up to 2 years
measure: Event free survival (EFS) rate
timeFrame: Up to 2 years
measure: Overall survival (OS) rate
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
Study officials:
affiliation: Columbia University
name: Monica Bhatia, MD
role: PRINCIPAL_INVESTIGATOR
References: