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

Acute Myeloid Leukemia Clinical Trial

— High Risk  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00669890
• Other study ID #: AAAA2533
• Secondary ID: CHNY-01-515
• Status: Terminated
• Phase: Phase 1
• First received: April 29, 2008
• Last updated: April 20, 2015
• Start date: May 2004
• Est. completion date: December 2013

Study information

• Verified date: April 2015
• Source: New York Medical College
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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)

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 12
• Est. completion date: December 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 30 Years

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Juvenile Myelomonocytic Leukemia
• Leukemia
• Leukemia, Myeloid, Acute
• Leukemia, Myelomonocytic, Acute
• Leukemia, Myelomonocytic, Chronic
• Leukemia, Myelomonocytic, Juvenile
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia

Intervention

Drug:
• Gemtuzumab Ozogamicin
Dose Escalation
• Busulfan
Conditioning Regimen
• Cyclophosphamide
Conditioning Regimen
• Thymoglobulin
(Unrelated Donors only)
• Tacrolimus
GVHD Prophylaxis
• Mycophenolate Mofetil
GVHD Prophylaxis
• Methotrexate
GVHD Prophylaxis

Locations

Country	Name	City	State
United States	Morgan Stanley Children's Hospital of NYP	New York City	New York

Sponsors (1)

Lead Sponsor	Collaborator
New York Medical College

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	Changes, if applicable, of minimal residual disease (cytogenetics, FISH, RT-PCR) in patients with high risk CD33+ AML/JMML/MDS after AlloSCT.		1 year	No
Secondary	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	No
Secondary	Quality of life before and after GO, Bu/CY conditioning and AlloSCT in patients with high risk CD33+ AML/JMML/MDS		1 year	No

External Links

•   (Click on "Morgan Stanley Children's Hospital" and then "Clinical Services" and then "Blood & Marrow Transplantation")