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

NCT00014495 | Completed Phase 1 Results

• 3 other identifiers: 00-117MSKCC-00117NCI-H01-0071
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Leukemia; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose

  The maximum tolerated dose of bismuth Bi 213 monoclonal antibody M195 following cytarabine in patients with advanced myeloid malignancies.

  2 years

Study Arms (1)

bismuth Bi 213 monoclonal antibody M195 & cytarabine

EXPERIMENTAL

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

Interventions

filgrastim BIOLOGICAL

bismuth Bi 213 monoclonal antibody M195 & cytarabine

cytarabine DRUG

bismuth Bi 213 monoclonal antibody M195 & cytarabine

bismuth Bi213 monoclonal antibody M195 RADIATION

bismuth Bi 213 monoclonal antibody M195 & cytarabine

Eligibility Criteria

• Age: Up to 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Memorial Sloan - Kettering Cancer Center

New York, New York, 10021, United States

Location

Related Publications (2)

• 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) for acute myeloid leukemia. Clin Cancer Res. 2010 Nov 1;16(21):5303-11. doi: 10.1158/1078-0432.CCR-10-0382. Epub 2010 Sep 21.

  PMID: 20858843 RESULT

• 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.

  RESULT

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases; Leukemia, Myeloid, Acute; Leukemia, Myeloid, Accelerated Phase; Blast Crisis; Anemia, Refractory, with Excess of Blasts; Leukemia, Myelomonocytic, Chronic; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Myeloproliferative Disorders; Congenital Abnormalities

Interventions

Filgrastim; Cytarabine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes; Anemia, Refractory; Anemia; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Dr. Martin Tallman
• Organization: Memorial Sloan Kettering Cancer Center

tallmanm@mskcc.org

212-639-3842

Study Officials

• Joseph G. Jurcic, MD

  Memorial Sloan Kettering Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2001
• First Posted: January 27, 2003
• Study Start: November 1, 2000
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: January 22, 2016
• Results First Posted: January 22, 2016

Record last verified: 2015-12

Locations

US (1)