Clinical trial NCT00014495: Chemotherapy and Monoclonal Antibody Therapy in Treating Patients With Advanced Myeloid Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
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
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 32
Sex: ALL
Maximum age (years): 120
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: Maximum Tolerated Dose
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan - Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Joseph G. Jurcic, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.