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

NCT ID: NCT00669890

Last Updated: 2015-04-22

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-05-31
• Study Completion Date: 2013-12-31

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)

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.

Conditions

Acute Myeloid Leukemia; Juvenile Myelomonocytic Leukemia; Myelodysplastic Syndrome

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

study 515

Group Type: EXPERIMENTAL

Gemtuzumab Ozogamicin

Intervention Type: DRUG

Dose Escalation

Busulfan

Intervention Type: DRUG

Conditioning Regimen

Cyclophosphamide

Intervention Type: DRUG

Conditioning Regimen

Thymoglobulin

Intervention Type: DRUG

(Unrelated Donors only)

Tacrolimus

Intervention Type: DRUG

GVHD Prophylaxis

Mycophenolate Mofetil

Intervention Type: DRUG

GVHD Prophylaxis

Methotrexate

Intervention Type: DRUG

GVHD Prophylaxis

Interventions

Gemtuzumab Ozogamicin

Dose Escalation

Intervention Type: DRUG

Busulfan

Conditioning Regimen

Intervention Type: DRUG

Cyclophosphamide

Conditioning Regimen

Intervention Type: DRUG

Thymoglobulin

(Unrelated Donors only)

Intervention Type: DRUG

Tacrolimus

GVHD Prophylaxis

Intervention Type: DRUG

Mycophenolate Mofetil

GVHD Prophylaxis

Intervention Type: DRUG

Methotrexate

GVHD Prophylaxis

Intervention Type: DRUG

Other Intervention Names

Gemtuzumab; Busulfex; Endoxan; Cytoxan; ATG; FK506; MMF; MTX

Eligibility Criteria

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.

• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

New York Medical College

OTHER

Sponsor Role: lead

Responsible Party

Mitchell Cairo

Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mitchell S Cairo, MD

Role: STUDY_CHAIR

Columbia University

Locations

Morgan Stanley Children's Hospital of NYP

New York, New York, United States

Countries

United States

Other Identifiers

CHNY-01-515

Identifier Type: OTHER

Identifier Source: secondary_id

AAAA2533

Identifier Type: -

Identifier Source: org_study_id