Allogeneic Stem Cell Transplantation Followed By Targeted Immune Therapy In Average Risk Leukemia

Myelodysplastic Syndrome Clinical Trial

— AML/MDS/JMML  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01020539
• Other study ID #: AAAA6378
• Secondary ID: CHNY-504
• Status: Completed
• Phase: Phase 1
• Start date: September 11, 2002
• Est. completion date: December 2020

Study information

• Verified date: August 2021
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: December 2020
• Est. primary completion date: July 20, 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 30 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Myelogenous Leukemia
• Juvenile Myelomonocytic Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Leukemia, Myelomonocytic, Acute
• Leukemia, Myelomonocytic, Chronic
• Leukemia, Myelomonocytic, Juvenile
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• Fludarabine
Conditioning Regimen
• Busulfan
Conditioning Regimen
• GVHD Prophylaxis
Can be FK506 (Tacrolimus/Prograf®), mycophenolate mofetil ((MMF)/Cellcept®), or methotrexate (MTX, amethopterin)
• Gemtuzumab Ozogamicin
Dose Escalation
• Anti-Thymocyte Globulin
Unrelated Donors only
• Isotretinoin
JMML patients only

Locations

Country	Name	City	State
United States	Columbia University Medical Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Columbia University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximal tolerated and/or biologically active dose of Gemtuzumab Ozogamicin (GO)	To determine the maximal tolerated and/or biologically active dose of Gemtuzumab Ozogamicin (GO) (anti CD33 immunotoxin) therapy following reduced intensity (RI) allogeneic stem cell transplantation (alloSCT) in patients with average risk AML/JMML/MDS.	Up to 2 years
Secondary	Change of minimal residual disease	To measure the changes, if applicable, of minimal residual disease prior to and after consolidation therapy with targeted immunotherapy in average risk AML/JMML/MDS post RI AlloSCT.	Day 60, Day 100, Day 180, 1 year, 2 years
Secondary	Incidence of minor histocompatibility antigen (MHA) expression on acute myeloid leukemia (AML) tissue	To measure the minor histocompatibility antigen expression on AML tissue, donor and recipient, and the incidence of development of MHA specific cytotoxic T-lymphocytes (CTLs).	Up to 2 years
Secondary	Degree of mixed/complete donor chimerism	To determine the degree of mixed/complete donor chimerism after RI AlloSCT in patients with average risk AML/JMML/MDS.	Up to 2 years
Secondary	Event free survival (EFS) rate	To determine event free survival (EFS) after RI AlloSCT and targeted immunotherapy in patients with average risk AML/JMML/MDS.	Up to 2 years
Secondary	Overall survival (OS) rate	To determine overall survival (OS) after RI AlloSCT and targeted immunotherapy in patients with average risk AML/JMML/MDS.	Up to 2 years