Radiolabeled Monoclonal Antibody Therapy and Etoposide Followed by Peripheral Stem Cell Transplantation in Treating Patients With Advanced Myelodysplastic Syndrome or Refractory Leukemia

Study Overview
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Brief Summary
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RATIONALE: Radiolabeled monoclonal antibodies can locate cancer cells and deliver radiation to them without harming normal cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Peripheral stem cell transplantation may allow the doctor to give higher doses of radiation and chemotherapy drugs and kill more cancer cells. PURPOSE: Phase I trial to study the effectiveness of radiolabeled monoclonal antibody therapy plus etoposide followed by peripheral stem cell transplantation in treating patients who have advanced myelodysplastic syndrome or refractory leukemia.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose of yttrium Y 90 humanized monoclonal antibody M195 when combined with etoposide as a preparative regimen for autologous peripheral blood stem cell transplantation in patients with advanced myelodysplastic syndrome or refractory leukemia. Determine the qualitative toxicities associated with this regimen in this patient population. Assess preliminary information on engraftment following this conditioning regimen in these patients. OUTLINE: This is a dose escalation study of yttrium Y 90 humanized monoclonal antibody M195 (Y90 MOAB M195). Patients receive Y90 MOAB M195 IV over 40 minutes once between days -12 to -9 and etoposide IV over several hours on day -3. Peripheral blood stem cells or bone marrow are reinfused on day 0. Patients receive filgrastim (G-CSF) subcutaneously beginning on day 1 until hematopoietic recovery. Cohorts of 3-6 patients receive escalating doses of Y90 MOAB M195 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 6 patients experience dose limiting toxicities. Patients are followed between days 10 and 14 and then monthly for 6 months. PROJECTED ACCRUAL: A total of 3-24 patients will be accrued for this study within 12 months.

Official Title
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Phase I Study of Yttrium-90 Labeled HuM195 Combined With Etoposide as a Conditioning Regimen for Autologous Stem Cell Transplantation in Patients With Advanced Myelodysplastic Syndrome and Refractory Leukemia

Conditions
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Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms

Intervention / Treatment
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* Biological: filgrastim
* Drug: etoposide
* Procedure: autologous bone marrow transplantation
* Procedure: peripheral blood stem cell transplantation
* Radiation: yttrium Y 90 monoclonal antibody M195


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: One of the following diagnoses: Acute myeloid leukemia Accelerated/blastic phase of a myeloproliferative disorder (i.e., greater than 10% blasts in bone marrow or presence of extramedullary disease) Myelodysplastic syndrome Acute lymphocytic leukemia with expression of CD33 Greater than 20% blast population No evidence of CNS disease Relapsed after previously achieving complete remission Must have previously had peripheral blood stem cells or bone marrow cells harvested and cryopreserved while in remission Greater than 25% of bone marrow blasts must be CD33 positive PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Not specified Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Not specified Renal: Creatinine no greater than 1.5 mg/dL OR Creatinine clearance at least 60 mL/min Cardiovascular: LVEF greater than 50% by ECG or MUGA No history of cardiomyopathy or symptomatic congestive heart failure Pulmonary: DLCO at least 50% predicted Other: Not pregnant or nursing Negative pregnancy test HIV negative No other concurrent active malignancy No known sensitivity to E. coli derived products PRIOR CONCURRENT THERAPY: Biologic therapy See Disease Characteristics Chemotherapy See Disease Characteristics Endocrine therapy Not specified Radiotherapy Not specified Surgery Not specified

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: filgrastim|nan|
|Drug: etoposide|nan|
|Procedure: autologous bone marrow transplantation|nan|
|Procedure: peripheral blood stem cell transplantation|nan|
|Radiation: yttrium Y 90 monoclonal antibody M195|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent adult acute myeloid leukemia, recurrent adult acute lymphoblastic leukemia, relapsing chronic myelogenous leukemia, accelerated phase chronic myelogenous leukemia, blastic phase chronic myelogenous leukemia, previously treated myelodysplastic syndromes, atypical chronic myeloid leukemia, BCR-ABL1 negative, myelodysplastic/myeloproliferative neoplasm, unclassifiable