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
18 Years
N/A
Both
Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms
Trial Information
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
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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Peter Maslak, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Memorial Sloan-Kettering Cancer Center
Authority:
United States: Federal Government
Study ID:
99-126
NCT ID:
NCT00006040
Start Date:
April 2000
Completion Date:
November 2003
Related Keywords:
- Leukemia
- Myelodysplastic Syndromes
- Myelodysplastic/Myeloproliferative Neoplasms
- 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
- Neoplasms
- Leukemia
- Myelodysplastic Syndromes
- Preleukemia
- Myeloproliferative Disorders
- Myelodysplastic-Myeloproliferative Diseases
Name | Location |
|---|---|
| Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
