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Allogeneic Stem Cell Transplantation Followed By Targeted Immune Therapy In Average Risk Leukemia (AML/MDS/JMML)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Monica Bhatia, Columbia University
ClinicalTrials.gov Identifier:
NCT01020539
First received: November 23, 2009
Last updated: May 18, 2012
Last verified: May 2012
History of Changes
  Purpose

Allogeneic stem cell transplantation (AlloSCT) followed by targeted immune therapy Gemtuzumab Ozogamicin patients with AML/JMML/MDS will be safe and well tolerated.


Condition Intervention Phase
Acute Myelogenous Leukemia
Myelodysplastic Syndrome
Juvenile Myelomonocytic Leukemia
 Drug: Fludarabine
Drug: Busulfan
Drug: FK506/MMF/ MTX
Drug: GEMTUZUMAB OZOGAMICIN
Drug: Thymoglobulin
Drug: cis-RA
 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: Allogeneic Stem Cell Transplantation Followed By Targeted Immune Therapy In Average Risk Acute Myelogenous Leukemia/Myelodysplastic Syndrome/Juvenile Myelomonocytic Leukemia (Aml/Mds/Jmml)

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Columbia University:

Primary Outcome Measures:
  • To determine the feasibility and toxicity of a Reduced Intensity (RI) regimen, AlloSCT followed by targeted immune therapy, Gemtuzumab Ozogamicin (GO) , in average risk AML/JMML/MDS. [ Time Frame: Day 60, Day 100, Day 180, 1 year, 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 [ Time Frame: Day 60, Day 100, Day 180, 1 year, 2 years ] [ Designated as safety issue: Yes ]
  • To measure the minor histocompatibility antigen expression on AML tissue, donor and recipient, and the development of MHA specific CTLs post [ Time Frame: Day 60, Day 100, Day 180, 1 year, 2 years ] [ Designated as safety issue: No ]
  • To determine the degree of mixed/complete donor chimerism after RI AlloSCT in patients with average risk AML/JMML/MDS. [ Time Frame: Day 60, Day 100, Day 180, 1 year, 2 years ] [ Designated as safety issue: No ]
  • To determine event free survival (EFS) and overall survival (OS) after RI AlloSCT and targeted immunotherapy in patients with average risk AML/JMML/MDS [ Time Frame: Day 60, Day 100, Day 180, 1 year, 2 years ] [ Designated as safety issue: Yes ]
  • To estimate the risk of acute and chronic GVHD following RI AlloSCT and FK506/MMF GVHD prophylaxis in patients with average risk AML/JMML/MDS [ Time Frame: Day 60, Day 100, Day 180, 1 year, 2 years ] [ Designated as safety issue: Yes ]
  • To determine the maximal tolerated and/or biologically active dose of Gemtuzumab Ozogamicin (GO) (anti CD33 immunotoxin) therapy following RI AlloSCT in patients with average risk AML/JMML/MDS. [ Time Frame: Day 60, Day 100, Day 180, 1 year, 2 years ] [ Designated as safety issue: Yes ]

Enrollment: 17
Study Start Date: September 2002
Estimated Study Completion Date: September 2013
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Matched Family Donor
Stem Cell Transplant will be performed using the matched family donor SCT.
 Drug: Fludarabine
Conditioning Regimen
Other Name: Fludarabine
Drug: Busulfan
Conditioning Regimen
Other Name: Busulfan
Drug: FK506/MMF/ MTX
GVHD Prophylaxis
Other Name: FK506/MMF/ MTX
Drug: GEMTUZUMAB OZOGAMICIN
Dose Escalation
Other Name: GEMTUZUMAB OZOGAMICIN
Experimental: Unrelated Donor
Stem Cell Transplant will be performed using Unrelated Donor SCT.
 Drug: Thymoglobulin
Unrelated Donors only
Other Name: Thymoglobulin
Drug: cis-RA
JMML patients only
Other Name: cis-RA

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 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

Ages Eligible for Study:   1 Month to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Disease Status

    • AML 1st CR with a matched family donor (excluding Downs Syndrome, 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
    • MDS and < 5% bone marrow myeloblasts at diagnosis (de novo patients only)
    • 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 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 ULN, or SGOT (AST) or SGPT (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:

    • DLCO > 40% by 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 CNS AML/JMML disease at time of preparative regimen
  • Secondary MDS
  • Female patients who are pregnant (positive HCG)
  • Karnofsky <70% or Lansky <50% if 10 years or less
  • Age >65 years
  • Seropositive for HIV
  • Patients consented to and registered on an upfront COG AML study with a matched family donor
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01020539

Locations
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
Sponsors and Collaborators
Columbia University
Investigators
Principal Investigator: Monica Bhatia, MD Columbia University
  More Information

Additional Information:
Click on "Morgan Stanley Children's Hospital" and then "Clinical Services" and then "Blood & Marrow Transplantation"  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Monica Bhatia, Assistant Clinical Professor of Pediatrics, Columbia University
ClinicalTrials.gov Identifier: NCT01020539     History of Changes
Other Study ID Numbers: AAAA6378, CHNY-504
Study First Received: November 23, 2009
Last Updated: May 18, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Columbia University:
AML
MDS
JMML

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
 Fludarabine monophosphate
Tacrolimus
Methotrexate
Mycophenolate mofetil
Fludarabine
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

ClinicalTrials.gov processed this record on May 16, 2013