Nonmyeloablative Preparative Regimen Using Mylotarg for Patients With High Risk Acute Myeloid Leukemia (AML), Acute Lymphocytic Leukemia (ALL), Chronic Myeloid Leukemia (CML) and Myelodysplastic Syndrome (MDS) - Full Text View

Sponsor:	M.D. Anderson Cancer Center
Collaborator:	Wyeth is now a wholly owned subsidiary of Pfizer
Information provided by:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00038805

Purpose

Primary Objective:

To determine the safety and maximum tolerated dose of CMA-676 as part of an intensive but nonmyeloablative preparative regimen in older or medically infirm patients undergoing mini-allogeneic peripheral blood stem cell transplantation

Secondary Objectives:

To evaluate response rates, engraftment kinetics and degree of chimerism achievable with this strategy.
To evaluate disease-free and overall survival and relapse rates.
To evaluate the need and ability to give multiple cycles of Mylotarg plus FA and mobilized DLI in patients not achieving complete remission.

Condition	Intervention	Phase
Leukemia	Drug: Mylotarg	Phase II Phase III

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 Using Mylotarg (CMA-676) Plus Nonmyeloablative Chemotherapy in Older or Medically Infirm Patients With High-Risk Acute Leukemia (ALL), Chronic Myelogenous Leukemia (CML) or Myelodysplastic Syndrome (MDS)

Resource links provided by NLM:

MedlinePlus related topics: Acute Lymphocytic Leukemia Acute Myeloid Leukemia Cancer Chronic Lymphocytic Leukemia Chronic Myeloid Leukemia Leukemia Myelodysplastic Syndromes

Drug Information available for: Gemtuzumab ozogamicin

U.S. FDA Resources

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:

Maximum Tolerated Dose (MTD) of CMA-676 [ Time Frame: Continual Reassessment Method (CRM); each cycle ] [ Designated as safety issue: Yes ]

Enrollment:	3
Study Start Date:	May 2001
Study Completion Date:	November 2004
Primary Completion Date:	November 2004 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Mylotarg	Drug: Mylotarg Other Name: CMA-676

Detailed Description:

Mylotarg is a novel immunoconjugate directed against the CD33 antigen found on most leukemia cells. This humanized murine IgG4 monoclonal antibody is tagged with the toxin, calicheamicin. In equal molar concentrations, calicheamicin is about 3200 times more potent than adriamycin. In a Phase I study involving adult patients with relapse AML, Mylotarg has been shown to have significant anti-leukemia activity with little toxicity. The most concerning side effects of Mylotarg were prolonged neutropenia and thrombocytopenia. Phase II studies have also demonstrated good efficacy with little toxicity.

The goal of this proposal is to include Mylotarg in a nonmyeloablative preparative regimen similar to FAI used at MD Anderson Cancer Center. The hypothesis is that Mylotarg will provide potent anti-leukemic effects without adding toxicity to the mini-allogeneic bone marrow transplant regimen. A more potent anti-leukemic response may increase the complete remission rates and induce a state of minimal residual disease (MRD). Therefore, the Graft vs. Leukemia (GVL) effect of allogeneic transplantation will have a better chance for success. In addition, the administration of donor cells after Mylotarg should ameliorate the cytopenias previously associated with Mylotarg. This medication likely will be well-tolerated.

Patients with high-risk hematopoietic malignancies that express CD33 (i.e. AML, ALL, CML and MDS) will be included. We will enroll older patients (>55 years old) or medically infirm patients who are unable to tolerate standard allogeneic bone marrow transplant. Patients will be evaluated at 28 days post-transplant for evidence of response. Those with residual disease may be eligible for additional Mylotarg given together with donor lymphocyte infusions. Additional courses of Mylotarg may improve overall survival in this poor prognosis group.

Eligibility

Ages Eligible for Study:	55 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients 12-75 years of age
Patients are eligible if deemed ineligible for conventional high dose chemotherapy programs because of concurrent medical conditions. Patients with refractory AML are eligible provided ejection fraction >= 35%; FEV1, FVC, or DLCO >= 40%; GPT < 3 x normal, direct bilirubin < 2.
Patients must have recovered from previous Grade III-IV toxicity due to prior antineoplastic therapy (except alopecia).
Patients with AML with induction failure, relapse or 2nd remission
Patients with MDS with IPI INT-2 or High-risk disease or CMML.
Patients with CML in accelerated phase or blast crisis
Patients with ALL with induction failure, relapse or 2nd remission
Patients receiving prior BMT are eligible. If myeloablative chemoradiotherapy was used in the prior transplant patients must be >90 days from transplant. If non-myeloablative therapy was used patients must be >30 days post-transplant.
Leukemia cells must express cell surface CD33 evaluated by flow cytometry in > 20% of leukemia cells.
Patients must have an HLA identical related donor capable of donating G-CSF stimulated peripheral blood stem cells using apheresis techniques. If patient has a contraindication to PBSC collection bone marrow can be used.
Patients must have a Zubrod PS <2, Cr <2.0, direct bilirubin <2, and transaminases SGPT <3x normal
Patients must have an estimated life expectancy > 3 months
Patient and donor must sign informed consent

Exclusion Criteria:

no uncontrolled active infection
no HIV disease
no pregnancy and no nursing
no active, uncontrolled CNS leukemia

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00038805

Locations

United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030

Sponsors and Collaborators

M.D. Anderson Cancer Center

Wyeth is now a wholly owned subsidiary of Pfizer

Investigators

Principal Investigator:

Marcos de Lima, MD

UT MD Anderson Cancer Center

More Information

Additional Information:

UT MD Anderson Cancer Center website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Marcos de Lima, MD / Professor, UT MD Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00038805 History of Changes
Other Study ID Numbers:	ID00-153
Study First Received:	June 5, 2002
Last Updated:	October 25, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:

High Risk Acute Myeloid Leukemia
Acute Lymphocytic Leukemia
Chronic Myeloid Leukemia
Myelodysplastic Syndrome
ALL
AML

MDS
CML
CMML
Nonmyeloablative Preparative Regimen
Mylotarg
CMA-676

Additional relevant MeSH terms:

Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders

Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Gemtuzumab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 12, 2012