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

NCT00669890 | Terminated Phase 1 DMC

• 2 other identifiers: AAAA2533CHNY-01-515
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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)

Conditions

Acute Myeloid Leukemia; Juvenile Myelomonocytic Leukemia; Myelodysplastic Syndrome

Keywords

AML; JMML; MDS; Allogenic Atem Cell Transplant; Gemtuzumab Ozogamicin

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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

Study Arms (1)

study 515

EXPERIMENTAL

Drug: Gemtuzumab Ozogamicin; Drug: Busulfan; Drug: Cyclophosphamide; Drug: Thymoglobulin; Drug: Tacrolimus; Drug: Mycophenolate Mofetil; Drug: Methotrexate

Interventions

Gemtuzumab Ozogamicin DRUG

Dose Escalation

Also known as: Gemtuzumab

study 515

Busulfan DRUG

Conditioning Regimen

Also known as: Busulfex

study 515

Cyclophosphamide DRUG

Conditioning Regimen

Also known as: Endoxan, Cytoxan

study 515

Thymoglobulin DRUG

(Unrelated Donors only)

Also known as: ATG

study 515

Tacrolimus DRUG

GVHD Prophylaxis

Also known as: FK506

study 515

Mycophenolate Mofetil DRUG

GVHD Prophylaxis

Also known as: MMF

study 515

Methotrexate DRUG

GVHD Prophylaxis

Also known as: MTX

study 515

Eligibility Criteria

• Age: Up to 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• New York Medical College: lead

Study Sites (1)

Morgan Stanley Children's Hospital of NYP

New York, New York, 10032, United States

Location

Related Links

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

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Juvenile; Myelodysplastic Syndromes

Interventions

Gemtuzumab; Busulfan; Cyclophosphamide; thymoglobulin; Tacrolimus; Mycophenolic Acid; Methotrexate

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Macrolides; Lactones; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Mitchell S Cairo, MD

  Columbia University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics

Study Record Dates

• First Submitted: April 29, 2008
• First Posted: May 1, 2008
• Study Start: May 1, 2004
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2013
• Last Updated: April 22, 2015

Record last verified: 2015-04

Locations

US (1)