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

Primary Purpose

Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
filgrastim
etoposide
autologous bone marrow transplantation
peripheral blood stem cell transplantation
yttrium Y 90 monoclonal antibody M195
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Memorial Sloan-Kettering Cancer Center

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
July 5, 2000
Last Updated
June 17, 2013
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00006040
Brief Title
Radiolabeled Monoclonal Antibody Therapy and Etoposide Followed by Peripheral Stem Cell Transplantation in Treating Patients With Advanced Myelodysplastic Syndrome or Refractory Leukemia
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2013
Overall Recruitment Status
Completed
Study Start Date
April 2000 (undefined)
Primary Completion Date
November 2003 (Actual)
Study Completion Date
November 2003 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
filgrastim
Intervention Type
Drug
Intervention Name(s)
etoposide
Intervention Type
Procedure
Intervention Name(s)
autologous bone marrow transplantation
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation
Intervention Type
Radiation
Intervention Name(s)
yttrium Y 90 monoclonal antibody M195

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter Maslak, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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