Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information

Alternate Title

Monoclonal Antibody Therapy in Treating Older Patients With Acute Myelogenous Leukemia Following Chemotherapy

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III, Phase II Treatment Closed 60 and over Pharmaceutical / Industry PDL-3-251 MSKCC-93131, NCI-V94-0469

Objectives

I.  Evaluate the safety of and tolerance to maintenance therapy with anti-CD33
humanized murine monoclonal antibody M195 (HuM195) vs. no treatment in elderly
patients with recently diagnosed or previously untreated acute myelogenous
leukemia in complete clinical remission after a standardized chemotherapeutic
regimen and granulocyte colony-stimulating factor.

II.  Assess disease-free and overall survival in these patients.

Entry Criteria

Disease Characteristics:

Newly diagnosed or previously untreated acute myelogenous leukemia of any FAB
subtype other than M3
  Morphologic and histologic confirmation of diagnosis required

No history of an antecedent hematologic disorder, i.e., myelodysplastic
syndrome (MDS) for more than 3 months
  Patients entered for Induction whose cytogenetic analysis later suggests
  prior existence of MDS are not randomized for further protocol therapy

No leukemia secondary to prior chemotherapy or radiotherapy

Prior/Concurrent Therapy:

No prior therapy

Patient Characteristics:

Age:
  60 and over

Performance status:
  Karnofsky 20-100%

Hepatic:
  Bilirubin less than 2.0 mg/dL (unless related to AML)

Renal:
  Creatinine less than 2.0 mg/dL (unless related to AML)

Cardiovascular:
  Left ventricular ejection fraction normal
  No active ischemia on EKG
  No significant cardiovascular disease, e.g.:
     No myocardial infarction within 6 months
     No congestive heart failure
     No arrhythmia
     No angina pectoris
     No uncontrolled hypertension

Pulmonary:
  No pulmonary dysfunction

Other:
  No central or peripheral nervous system impairment
  No uncontrolled or unstable diabetes
  No HIV antibody
  No serious infection uncontrolled by antibiotics
  No active second malignancy
  Effective contraception required in fertile patients during and for 3 months
     after treatment

Expected Enrollment

112 patients will be randomized for maintenance.  An accrual rate of 75 
patients/year is anticipated.

Outline

Patients in clinical CR following sequential treatment on Induction 1 and 
Induction 2 are randomized for Maintenance therapy on Arms I and II.

The following acronyms are used:
  ARA-C    Cytarabine, NSC-63878
  DHAD     Mitoxantrone, NSC-301739
  G-CSF    Granulocyte Colony-Stimulating Factor (Amgen), NSC-614629
  IDA      Idarubicin, NSC-256439
  HuM195   Recombinant anti-CD33 humanized murine monoclonal antibody M195
  VP-16    Etoposide, NSC-141540

Induction 1:  2-Drug Combination Chemotherapy with Hematologic Toxicity 
Attenuation.  ARA-C; IDA or DHAD or daunorubicin; with G-CSF.

Induction 2:  3-Drug Combination Chemotherapy with Hematologic Toxicity 
Attenuation.  DHAD or IDA or daunorubicin; VP-16 (+/-); ARA-C; with G-CSF.

Maintenance:

Arm I:  Monoclonal Antibody Therapy.  HuM195.

Arm II:  Observation.

Trial Contact Information

Trial Lead Organizations

Protein Design Labs, Incorporated

Eric Feldman, MD, Protocol chair		Ph: 914-594-4400