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

This study has been terminated.
(PI left institution)
Sponsor:
Information provided by (Responsible Party):
Mitchell Cairo, New York Medical College
ClinicalTrials.gov Identifier:
NCT00669890
First received: April 29, 2008
Last updated: October 25, 2011
Last verified: October 2011
  Purpose

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.


Condition Intervention 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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by New York Medical College:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 16
Study Start Date: May 2004
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   up to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Eligibility

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00669890

Locations
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
Investigators
Study Chair: Mitchell S Cairo, MD Columbia University
  More Information

Additional Information:
No publications provided

Responsible Party: Mitchell Cairo, Professor of Pediatrics, New York Medical College
ClinicalTrials.gov Identifier: NCT00669890     History of Changes
Other Study ID Numbers: AAAA2533, CHNY-01-515
Study First Received: April 29, 2008
Last Updated: October 25, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by New York Medical College:
AML
JMML
MDS
Allogenic Atem Cell Transplant
Gemtuzumab Ozogamicin

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Myelodysplastic-Myeloproliferative Diseases
Busulfan
Cyclophosphamide
Methotrexate
Mycophenolate mofetil
Tacrolimus
Gemtuzumab
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014