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Allogenic Stem Cell Transplantation in Patients With High Risk CD33+ AML/MDS/JMML (High Risk)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00669890
Recruitment Status : Terminated (PI left institution)
First Posted : May 1, 2008
Last Update Posted : April 22, 2015
Information provided by (Responsible Party):
Mitchell Cairo, New York Medical College

Brief Summary:

The addition of gemtuzumab ozogamicin (GO) in combination with Busulfan/Cyclophosphamide followed by AlloSCT in patients with high risk CD33+ AML/JMML/MDS will be safe and well tolerated.

This study will attempt to determine the maximum tolerated dose of the immune therapy (gemtuzumab) when given in combination with the myeloablative (high dose) drugs used in this study for allogeneic stem cell transplant. (Part A)

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Juvenile Myelomonocytic Leukemia Myelodysplastic Syndrome Drug: Gemtuzumab Ozogamicin Drug: Busulfan Drug: Cyclophosphamide Drug: Thymoglobulin Drug: Tacrolimus Drug: Mycophenolate Mofetil Drug: Methotrexate Phase 1

Detailed Description:
Gemtuzumab Ozogamicin (CMA-676) is a chemotherapeutic agent consisting of 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 leukemia 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 the complex that is internalized, upon which calicheamicin derivative is released with in the lysosomes of the myeloid cell. The free calicheamicin derivative then binds to the DNA, resulting in DNA double strand breaks and consequential cell death.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Gemtuzumab Ozogamicin in Combination With Busulfan and Cyclophosphamid and Allogenic Stem Cell Transplantation in Patients With High Risk CD33+ Acute Myelogenous Leukemia/Myelodysplastic Syndrome/Juvenile Myelomonocytic Leukemia
Study Start Date : May 2004
Actual Primary Completion Date : December 2012
Actual Study Completion Date : December 2013

Arm Intervention/treatment
Experimental: study 515 Drug: Gemtuzumab Ozogamicin
Dose Escalation
Other Name: Gemtuzumab

Drug: Busulfan
Conditioning Regimen
Other Name: Busulfex

Drug: Cyclophosphamide
Conditioning Regimen
Other Names:
  • Endoxan
  • Cytoxan

Drug: Thymoglobulin
(Unrelated Donors only)
Other Name: ATG

Drug: Tacrolimus
GVHD Prophylaxis
Other Name: FK506

Drug: Mycophenolate Mofetil
GVHD Prophylaxis
Other Name: MMF

Drug: Methotrexate
GVHD Prophylaxis
Other Name: MTX

Primary Outcome Measures :
  1. Maximal tolerated dose or tolerable dose of Gemtuzumab Ozogamicin (anti-CD33 immunotoxin) therapy combined with Busulfan/ Cyclophosphamide in the conditioning regimen prior to AlloSCT in patients with high risk CD33+ AML/JMML/MDS [ Time Frame: 1 year ]

Secondary Outcome Measures :
  1. Changes, if applicable, of minimal residual disease (cytogenetics, FISH, RT-PCR) in patients with high risk CD33+ AML/JMML/MDS after AlloSCT. [ Time Frame: 1 year ]
  2. Progression Free Survival (PFS), overall survival (OS), and disease free survival (DFS), (if applicable), following GO, Bu/CY and AlloSCT in patients with high risk CD33+ AML/JMML/MDS. [ Time Frame: 1 year ]
  3. Quality of life before and after GO, Bu/CY conditioning and AlloSCT in patients with high risk CD33+ AML/JMML/MDS [ Time Frame: 1 year ]

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


Inclusion Criteria:

Disease Status

  • AML Induction Failure
  • AML in 1st, 2nd, or 3rd Relapse (>10% bone marrow blasts)
  • AML greater than or equal to 3rd CR
  • MDS with >6% bone marrow blasts at diagnosis
  • Secondary MDS with less than or equal to 5% bone marrow myeloblasts at diagnosis
  • JMML with >6% bone marrow myeloblasts at diagnosis

Disease Immunophenotype Patients (AML only) receiving gemtuzumab ozogamicin must express minimum of >10% or =10% CD33 positivity. Patients with <10% CD33 positivity will not receive gemtuzumab ozogamicin.

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 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 1.5 x normal, or SGOT (AST) or SGPT (ALT) <2.0 x normal or =2.0 x normal
  • Adequate cardiac function defined as:
  • Shortening fraction of >27% by echocardiogram, or
  • Ejection fraction of >47% by radionuclide angiogram or echocardiogram
  • Adequate pulmonary function defined as:
  • DLCO >55% or =55% by PFT
  • 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 CNS AML/JMML/MDS disease at time of conditioning therapy
  • Female patients who are pregnant (positive HCG)
  • Karnofsky <50% or Lansky <50% if 10 years or less
  • Age >65 years
  • Has received gemtuzumab in the previous 30 days or has not recovered from prior gemtuzumab therapy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00669890

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United States, New York
Morgan Stanley Children's Hospital of NYP
New York City, New York, United States, 10032
Sponsors and Collaborators
New York Medical College
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Study Chair: Mitchell S Cairo, MD Columbia University

Additional Information:
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Responsible Party: Mitchell Cairo, Professor of Pediatrics, New York Medical College Identifier: NCT00669890     History of Changes
Other Study ID Numbers: AAAA2533
CHNY-01-515 ( Other Identifier: CU )
First Posted: May 1, 2008    Key Record Dates
Last Update Posted: April 22, 2015
Last Verified: April 2015
Keywords provided by Mitchell Cairo, New York Medical College:
Allogenic Atem Cell Transplant
Gemtuzumab Ozogamicin
Additional relevant MeSH terms:
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Leukemia, Myelomonocytic, Juvenile
Myelodysplastic Syndromes
Pathologic Processes
Neoplasms by Histologic Type
Leukemia, Myeloid
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Myelodysplastic-Myeloproliferative Diseases
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists