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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00006040
First received: July 5, 2000
Last updated: June 17, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Leukemia
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Neoplasms
Biological: filgrastim
Drug: etoposide
Procedure: autologous bone marrow transplantation
Procedure: peripheral blood stem cell transplantation
Radiation: yttrium Y 90 monoclonal antibody M195
Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Study Start Date: April 2000
Study Completion Date: November 2003
Primary Completion Date: November 2003 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00006040

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Study Chair: Peter Maslak, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00006040     History of Changes
Other Study ID Numbers: 99-126, CDR0000068055, NCI-G00-1815
Study First Received: July 5, 2000
Last Updated: June 17, 2013
Health Authority: United States: Federal Government

Keywords provided by Memorial Sloan-Kettering Cancer Center:
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

Additional relevant MeSH terms:
Neoplasms
Leukemia
Myelodysplastic Syndromes
Preleukemia
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Lenograstim
Etoposide
Etoposide phosphate
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on July 29, 2014