Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II, Phase I	Treatment	Closed	Not specified	NCI	MSKCC-00117 NCI-H01-0071, NCT00014495

Objectives

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

Entry 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

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

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

Expected Enrollment

A total of 3-39 patients will be accrued for this study within 3 years.

Outcomes

Maximum tolerated dose
Antileukemic effects
Toxicity
Pharmacology, biodistribution, and dosimetry

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.

Mulford DA, Pandit-Taskar N, McDevitt MR, et al.: Sequential therapy with cytarabine and bismuth-213 (213Bi)-labeled-HuM195 (Anti-CD33) for acute myeloid leukemia (AML). [Abstract] Blood 104 (11): A-1790, 2004.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Joseph Jurcic, MD, Protocol chair		Ph: 212-639-2955; 800-525-2225 Email: jurcicj@mskcc.org

Registry Information
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
Trial Start Date		2000-11-14
Trial Completion Date		2010-12-13 (estimated)
Registered in ClinicalTrials.gov		NCT00014495
Date Submitted to PDQ		2001-02-15
Information Last Verified		2008-10-22
NCI Grant/Contract Number		CA33049, CA08748

Back to Top