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

December 17, 2015 updated by: Memorial Sloan Kettering Cancer Center

Phase I/II Trial Of Sequential Therapy With Cytarabine And Bismuth-213-Labeled HuM195 (Humanized Anti-CD33) In Patients With Advanced Myeloid Malignancies

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

32

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10021
        • Memorial Sloan - Kettering Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 120 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
Drug: cytarabine
Biological: filgrastim
Radiation: bismuth Bi213 monoclonal antibody M195

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Tolerated Dose
Time Frame: 2 years
The maximum tolerated dose of bismuth Bi 213 monoclonal antibody M195 following cytarabine in patients with advanced myeloid malignancies.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2000

Primary Completion (Actual)

December 1, 2009

Study Completion (Actual)

December 1, 2009

Study Registration Dates

First Submitted

April 10, 2001

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

January 22, 2016

Last Update Submitted That Met QC Criteria

December 17, 2015

Last Verified

December 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 00-117
  • MSKCC-00117
  • NCI-H01-0071

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Myelodysplastic Syndromes

Clinical Trials on cytarabine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Hong Kong

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe