Chemotherapy and Monoclonal Antibody Therapy in Treating Patients With Advanced Myeloid Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00014495
First received: April 10, 2001
Last updated: April 16, 2013
Last verified: April 2013
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining monoclonal antibody therapy with chemotherapy may kill more cancer cells.

PURPOSE: Phase I/II trial to study the effectiveness of combining chemotherapy and monoclonal antibody therapy in treating patients who have advanced myeloid cancer.


Condition Intervention Phase
Leukemia
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Neoplasms
Biological: filgrastim
Drug: cytarabine
Radiation: bismuth Bi213 monoclonal antibody M195
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Trial Of Sequential Therapy With Cytarabine And Bismuth-213-Labeled HuM195 (Humanized Anti-CD33) In Patients With Advanced Myeloid Malignancies

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Maximum tolerated dose [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Antileukemic effects [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Pharmacology, biodistribution, and dosimetry [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 32
Study Start Date: November 2000
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: bismuth Bi 213 monoclonal antibody M195 & cytarabine

Patients receive cytarabine IV continuously on days 1-5. Beginning between days 7 and 14, patients receive Bi213 MOAB M195 IV over 5 minutes up to 4 times daily over 1-4 days. Patient also receive filgrastim (G-CSF) subcutaneously daily beginning 24 hours after the final Bi213 MOAB M195 infusion and continuing until blood counts recover. Treatment continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 3 to 6 patients receive escalating doses of Bi213 MOAB M195 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, subsequent patients are treated at the MTD.

Patients are followed twice weekly for 4 weeks and then monthly for 3 months

Biological: filgrastim Drug: cytarabine Radiation: bismuth Bi213 monoclonal antibody M195

Detailed Description:

OBJECTIVES:

  • Determine the maximum tolerated dose of bismuth Bi 213 monoclonal antibody M195 following cytarabine in patients with advanced myeloid malignancies.
  • Determine the antileukemic effects of this treatment in this patient population.
  • Determine the toxicity of this treatment in this patient population.
  • Determine the complete remission rate of patients treated with this treatment regimen.

OUTLINE: This is a dose escalation study of bismuth Bi 213 monoclonal antibody M195 (Bi213 MOAB M195).

Patients receive cytarabine IV continuously on days 1-5. Beginning between days 7 and 14, patients receive Bi213 MOAB M195 IV over 5 minutes up to 4 times daily over 1-4 days. Patient also receive filgrastim (G-CSF) subcutaneously daily beginning 24 hours after the final Bi213 MOAB M195 infusion and continuing until blood counts recover. Treatment continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 3 to 6 patients receive escalating doses of Bi213 MOAB M195 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, subsequent patients are treated at the MTD.

Patients are followed twice weekly for 4 weeks and then monthly for 3 months.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • One of the following diagnoses:

    • Pathologically confirmed acute myeloid leukemia (AML) meeting one of the following criteria:

      • Newly diagnosed AML, over age 60, and not eligible for higher priority protocols
      • Newly diagnosed AML and unable to receive anthracycline-containing or high-dose cytarabine-containing regimens
      • AML in relapse
      • AML refractory to two courses of standard induction chemotherapy or one course of high-dose cytarabine-containing induction chemotherapy
    • Chronic myelogenous leukemia in accelerated phase or myeloid blast crisis
    • Refractory anemia with excess blasts (RAEB), RAEB in transformation, or chronic myelomonocytic leukemia
  • More than 25% of bone marrow blasts must be CD33 positive
  • Not a candidate for immediate bone marrow transplantation with a HLA-compatible donor
  • No active CNS leukemia

PATIENT CHARACTERISTICS:

Age:

  • Not specified

Performance status:

  • Karnofsky 60-100%

Life expectancy:

  • Not specified

Hematopoietic:

  • Not specified

Hepatic:

  • Bilirubin no greater than 2 mg/dL (unless due to leukemia or Gilbert's disease)
  • Alkaline phosphatase no greater than 2.5 times upper limit of normal (ULN)
  • AST no greater than 2.5 times ULN

Renal:

  • Creatinine less than 2 mg/dL OR
  • Creatinine clearance greater than 60 mL/min

Cardiovascular:

  • No New York Heart Association class III or IV cardiac disease

Pulmonary:

  • No pulmonary disease

Other:

  • No detectable antibodies to monoclonal antibody M195
  • No serious active uncontrolled infection
  • No other concurrent active malignancy requiring therapy
  • No other serious or life-threatening conditions that would preclude study
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • At least 3 weeks since prior biologic therapy and recovered

Chemotherapy:

  • See Disease Characteristics
  • Prior hydroxyurea allowed if discontinued before study treatment
  • At least 3 weeks since other prior chemotherapy and recovered

Endocrine therapy:

  • Not specified

Radiotherapy:

  • At least 3 weeks since prior radiotherapy and recovered

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: NCT00014495

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: Joseph G. Jurcic, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
Publications:
Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00014495     History of Changes
Other Study ID Numbers: 00-117, MSKCC-00117, NCI-H01-0071
Study First Received: April 10, 2001
Last Updated: April 16, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
recurrent childhood acute myeloid leukemia
recurrent adult acute myeloid leukemia
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
untreated adult acute myeloid leukemia
untreated childhood acute myeloid leukemia and other myeloid malignancies
refractory anemia with excess blasts
refractory anemia with excess blasts in transformation
chronic myelomonocytic leukemia
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
childhood chronic myelogenous leukemia
atypical chronic myeloid leukemia, BCR-ABL1 negative
myelodysplastic/myeloproliferative neoplasm, unclassifiable
adult acute myeloid leukemia with t(8;21)(q22;q22)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with t(15;17)(q22;q12)
childhood myelodysplastic syndromes

Additional relevant MeSH terms:
Neoplasms
Myelodysplastic Syndromes
Preleukemia
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Leukemia
Syndrome
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms by Histologic Type
Disease
Pathologic Processes
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Cytarabine
Bismuth
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Antacids

ClinicalTrials.gov processed this record on September 22, 2014