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

Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00014495
• Other study ID #: 00-117
• Secondary ID: MSKCC-00117NCI-H
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: April 10, 2001
• Last updated: December 17, 2015
• Start date: November 2000
• Est. completion date: December 2009

Study information

• Verified date: December 2015
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 120 Years

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Myelodysplastic Syndromes
• Myelodysplastic-Myeloproliferative Diseases
• Myelodysplastic/Myeloproliferative Neoplasms
• Myeloproliferative Disorders
• Preleukemia

Intervention

Biological:
• filgrastim

Drug:
• cytarabine

Radiation:
• bismuth Bi213 monoclonal antibody M195

Locations

Country	Name	City	State
United States	Memorial Sloan - Kettering Cancer Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (2)

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.

Rosenblat TL, McDevitt MR, Mulford DA, Pandit-Taskar N, Divgi CR, Panageas KS, Heaney ML, Chanel S, Morgenstern A, Sgouros G, Larson SM, Scheinberg DA, Jurcic JG. Sequential cytarabine and alpha-particle immunotherapy with bismuth-213-lintuzumab (HuM195) — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose	The maximum tolerated dose of bismuth Bi 213 monoclonal antibody M195 following cytarabine in patients with advanced myeloid malignancies.	2 years	Yes