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

Information source: Columbia University
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Acute Myelogenous Leukemia; Myelodysplastic Syndrome; Juvenile Myelomonocytic Leukemia

Intervention: Fludarabine (Drug); Busulfan (Drug); Graft-versus-host disease (GVHD) Prophylaxis (Drug); Gemtuzumab Ozogamicin (Drug); Anti-Thymocyte Globulin (Drug); Isotretinoin (Drug)

Phase: Phase 1

Status: Active, not recruiting

Sponsored by: Columbia University

Official(s) and/or principal investigator(s):
Monica Bhatia, MD, Principal Investigator, Affiliation: Columbia University

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.

Clinical Details

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 design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Maximal tolerated and/or biologically active dose of Gemtuzumab Ozogamicin (GO)

Secondary outcome:

Change of minimal residual disease

Minor histocompatibility antigen (MHA) expression on acute myeloid leukemia (AML) tissue

Degree of mixed/complete donor chimerism

Event free survival (EFS) rate

Overall survival (OS) rate

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

Minimum age: 1 Month. Maximum age: 64 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Disease Status

- Acute myeloid leukemia (AML) 1st complete remission (CR) with a matched family

donor (excluding Downs Syndrome, Acute Promyelocytic Leukemia (APL), 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)] 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

- Disease must express a minimum of >10% CD33 positivity for patients with AML

- 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

- Female patients who are pregnant (positive human chorionic gonadotropin(hCG))

- Karnofsky <70% or Lansky <50% if 10 years or less

- Age >65 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

Locations and Contacts

Columbia University Medical Center, New York, New York 10032, United States
Additional Information

Click on "Morgan Stanley Children's Hospital" and then "Clinical Services" and then "Blood & Marrow Transplantation"

Starting date: January 2003
Last updated: March 9, 2015

Page last updated: August 23, 2015

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