Primary Objective: To determine the safety and maximum tolerated dose of Mylotarg as part of a reduced-intensity preparative regimen patients undergoing related, mismatched-related or matched unrelated donor transplantation.

Secondary Objectives: 1. To evaluate response rates, engraftment kinetics and degree of chimerism achievable with this strategy. 2. To evaluate the incidence and severity of GVHD in this population 3. To evaluate disease-free and overall survival and relapse rates.

Condition	Treatment or Intervention	Phase
Acute Myelogenous Leukemia Myelodysplastic Syndrome Chronic Lymphocytic Leukemia	Drug: Mylotarg	Phase I Phase II

Allogeneic bone marrow transplantation is an effective first line and salvage therapy in-patients with AML, CML or MDS. In the past, allogeneic transplantation has been limited to younger patients due to the increased risk of regimen-related toxicity and graft-versus-host disease (GVHD). In order to expand the use of alloBMT to older patients, researchers at MD Anderson Cancer Center have pioneered the use of nonmyeloablative preparative therapy for allogeneic transplantation. Nonmyeloablative therapy utilizes low-dose chemotherapy in order to decrease regimen-related toxicity. The low-dose chemotherapy induces host immunosuppression, spares toxicity, and allows engraftment of donor stem cells. The goal of this therapy is to exploit the anti-tumor effects of donor immune cells.

One shortcoming of nonmyeloablative transplantation is an increased risk of disease relapse, especially in patients with high-risk disease. This includes patients with relapse or refractory AML, advanced MDS and advanced CML. Mylotarg is a novel immunotoxin directed against the CD33 antigen found on most AML, CML and MDS clones. Mylotarg has been shown to have significant anti-leukemia activity with little toxicity. The goal of this Phase I/II protocol is to evaluate the safety and efficacy of adding escalating doses of Mylotarg to Fludarabine and Melphalan in patients with CML, MDS or acute myelogenous leukemia undergoing related, mismatch-related or matched unrelated donor allogeneic transplantation. The hypothesis is that Mylotarg will provide potent anti-leukemic effects without additional toxicity. Mylotarg, Melphalan, and Fludarabine have non-overlapping toxicities. A more potent anti-leukemic response may increase the complete remission rates and induce a state of minimal residual disease (MRD). Therefore, the GVL effect will have a better chance for success.

Ages Eligible for Study:  55 Years   -   75 Years,  Genders Eligible for Study:  Both

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 always eligible if ejection fraction > 35, FEV1, FVC, or DLCO > 40%, abnormal LFT's.
• Patients must have recovered from previous Grade III-IV toxicity due to prior anti-neoplastic therapy (except alopecia).
• Patients with the following disease categories will be eligible: a. AML with induction failure, relapse or 2nd remission b. MDS with IPI INT-2 or High-risk disease (Appendix 4) or CMML c. CML in accelerated phase or blast crisis d. Interferon or STI resistant CML not eligible for conventional stem cell transplant
• 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-compatible related donor (6/6 or 5/6 HLA-match) capable of donating bone marrow or G-CSF stimulated peripheral blood stem cells using aphereses techniques or a 6/6 HLA matched unrelated bone marrow donor (serologic matching for Class I, molecular matching for DR?1).
• Patients must have a ECOG PS<2 (Appendix 6), Cr<2.0, bilirubin <2, and (SGPT) <3x normal
• Patients must have an estimated life expectancy > 3 months
• Patient and donor must sign informed consent. Unrelated donors will be consented according to the National Donor Marrow Registry policy

Exclusion Criteria:

• uncontrolled active infection
• HIV disease
• pregnancy and nursing
• active, uncontrolled CNS leukemia

Texas
      MD Anderson Cancer Center, Houston,  Texas,  77030,  United States; Recruiting

Study ID Numbers:  ID01-010
Record last reviewed:  June 2004
Record first received:  June 5, 2002
ClinicalTrials.gov Identifier:  NCT00038831
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2004-10-29