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Phase I/II Trial Of Sequential Therapy With Cytarabine And Bismuth-213-Labeled HuM195 (Humanized Anti-CD33) In Patients With Advanced Myeloid Malignancies


Phase 1/Phase 2
N/A
N/A
Not Enrolling
Both
Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms

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Trial Information

Phase I/II Trial Of Sequential Therapy With Cytarabine And Bismuth-213-Labeled HuM195 (Humanized Anti-CD33) In Patients With Advanced Myeloid Malignancies


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.

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

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Maximum tolerated dose

Outcome Time Frame:

2 years

Safety Issue:

Yes

Principal Investigator

Joseph G. Jurcic, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

00-117

NCT ID:

NCT00014495

Start Date:

November 2000

Completion Date:

December 2009

Related Keywords:

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

Name

Location
Memorial Sloan - Kettering Cancer Center New York, New York  10021