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

Sponsor

New York Medical College (Other)

Overall Status

Terminated

CT.gov ID

NCT00669890

Collaborator

(none)

Enrollment

Location

Arm

115

Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

12 participants

Allocation:

N/A

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 1, 2004

Actual Primary Completion Date :

Dec 1, 2012

Actual Study Completion Date :

Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: study 515	Drug: Gemtuzumab Ozogamicin Dose Escalation Other Names: Gemtuzumab Drug: Busulfan Conditioning Regimen Other Names: Busulfex Drug: Cyclophosphamide Conditioning Regimen Other Names: Endoxan Cytoxan Drug: Thymoglobulin (Unrelated Donors only) Other Names: ATG Drug: Tacrolimus GVHD Prophylaxis Other Names: FK506 Drug: Mycophenolate Mofetil GVHD Prophylaxis Other Names: MMF Drug: Methotrexate GVHD Prophylaxis Other Names: MTX

Arm

Intervention/Treatment

Experimental: study 515

Drug: Gemtuzumab Ozogamicin

Dose Escalation

Other Names:

Gemtuzumab

Drug: Busulfan

Conditioning Regimen

Other Names:

Busulfex

Drug: Cyclophosphamide

Conditioning Regimen

Other Names:

Endoxan

Cytoxan

Drug: Thymoglobulin

(Unrelated Donors only)

Other Names:

ATG

Drug: Tacrolimus

GVHD Prophylaxis

Other Names:

FK506

Drug: Mycophenolate Mofetil

GVHD Prophylaxis

Other Names:

MMF

Drug: Methotrexate

GVHD Prophylaxis

Other Names:

MTX

Outcome Measures

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 [1 year]

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. [1 year]
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. [1 year]
Quality of life before and after GO, Bu/CY conditioning and AlloSCT in patients with high risk CD33+ AML/JMML/MDS [1 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 30 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.