Leukemia, Myelodysplastic/Myeloproliferative Neoplasms, Myelodysplastic Syndromes
Conditions
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
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.
Interventions
BIOLOGICALfilgrastim
DRUGcytarabine
RADIATIONbismuth Bi213 monoclonal antibody M195
Sponsors
National Cancer Institute (NCI)
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 120 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose | 2 years | The maximum tolerated dose of bismuth Bi 213 monoclonal antibody M195 following cytarabine in patients with advanced myeloid malignancies. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bismuth-labeled HuM195 (0.5 mCi/kg) 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. | 3 |
| Bismuth-labeled HuM195 (0.75 mCi/kg) 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. | 3 |
| Bismuth-labeled HuM195 (1 mCi/kg) 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. | 20 |
| Bismuth-labeled HuM195 (1.25 mCi/kg) 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. | 6 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Clinical deterioration | 0 | 0 | 0 | 1 |
| Overall Study | Death | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Bismuth-labeled HuM195 (0.5 mCi/kg) | Bismuth-labeled HuM195 (0.75 mCi/kg) | Bismuth-labeled HuM195 (1 mCi/kg) | Bismuth-labeled HuM195 (1.25 mCi/kg) | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 11 Participants | 5 Participants | 18 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 2 Participants | 9 Participants | 1 Participants | 14 Participants |
| Region of Enrollment United States | 3 participants | 3 participants | 20 participants | 6 participants | 32 participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 8 Participants | 1 Participants | 10 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 12 Participants | 5 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 17 / 20 | 6 / 6 |
| serious Total, serious adverse events | 2 / 3 | 2 / 3 | 3 / 20 | 3 / 6 |
Outcome results
Primary
Maximum Tolerated Dose
The maximum tolerated dose of bismuth Bi 213 monoclonal antibody M195 following cytarabine in patients with advanced myeloid malignancies.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bismuth Bi 213 Monoclonal Antibody M195 & Cytarabine | Maximum Tolerated Dose | 1 mCi/kg |