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: December 18, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Acute Myelogenous Leukemia
Myelodysplastic Syndrome
Juvenile Myelomonocytic Leukemia
Drug: Fludarabine
Drug: Busulfan
Drug: Graft-versus-host disease (GVHD) Prophylaxis
Drug: Gemtuzumab Ozogamicin
Drug: Anti-Thymocyte Globulin
Drug: Isotretinoin
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:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Maximal tolerated and/or biologically active dose of Gemtuzumab Ozogamicin (GO) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change of minimal residual disease [ Time Frame: Day 60, Day 100, Day 180, 1 year, 2 years ] [ Designated as safety issue: Yes ]
    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.

  • Minor histocompatibility antigen (MHA) expression on acute myeloid leukemia (AML) tissue [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    To measure the minor histocompatibility antigen expression on AML tissue, donor and recipient, and the development of MHA specific cytotoxic T-lymphocytes (CTLs).

  • Degree of mixed/complete donor chimerism [ Time Frame: Up to 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.

  • Event free survival (EFS) rate [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    To determine event free survival (EFS) after RI AlloSCT and targeted immunotherapy in patients with average risk AML/JMML/MDS.

  • Overall survival (OS) rate [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    To determine overall survival (OS) after RI AlloSCT and targeted immunotherapy in patients with average risk AML/JMML/MDS.


Enrollment: 18
Study Start Date: January 2003
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: December 2013 (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: Fludara®
Drug: Busulfan
Conditioning Regimen
Other Name: Busulfex®
Drug: Graft-versus-host disease (GVHD) Prophylaxis
Can be FK506 (Tacrolimus/Prograf®), mycophenolate mofetil ((MMF)/Cellcept®), or methotrexate (MTX, amethopterin)
Drug: Gemtuzumab Ozogamicin
Dose Escalation
Other Name: Mylotarg®
Experimental: Unrelated Donor
Stem Cell Transplant will be performed using Unrelated Donor SCT.
Drug: Anti-Thymocyte Globulin
Unrelated Donors only
Other Name: Thymoglobulin®
Drug: Isotretinoin
JMML patients only
Other Names:
  • Accutane®
  • 13-cis-Retinoic Acid
  • 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 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

Ages Eligible for Study:   1 Month to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:
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: December 18, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Columbia University:
Allogeneic Stem Cell Transplantation
Targeted Immune Therapy
Acute Myelogenous Leukemia
Myelodysplastic Syndrome
Juvenile Myelomonocytic Leukemia
AML
MDS
JMML

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Myelodysplastic-Myeloproliferative Diseases
Neoplasms
Neoplasms by Histologic Type
Pathologic Processes
Precancerous Conditions
Antilymphocyte Serum
Gemtuzumab
Isotretinoin
Antineoplastic Agents
Dermatologic Agents
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014