Clinical Protocol for a Phase II Study of Leridistim (SC-70935) in Adult Patients (Age>55) With Acute Myeloid Leukemia (AML) Receiving Chemotherapy With the Cytarabine and Daunorubicin "7+3" Regimen


Phase 2
55 Years
N/A
Not Enrolling
Both
Anemia, Leukemia, Neutropenia, Thrombocytopenia

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Trial Information

Clinical Protocol for a Phase II Study of Leridistim (SC-70935) in Adult Patients (Age>55) With Acute Myeloid Leukemia (AML) Receiving Chemotherapy With the Cytarabine and Daunorubicin "7+3" Regimen


OBJECTIVES: I. Determine the maximum tolerated dose or hematopoietically active dose of
leridistim administered with induction chemotherapy in older patients with acute myeloid
leukemia. II. Determine the effect of leridistim on the duration of grade IV neutropenia
during the induction course in these patients. III. Determine the safety and tolerability of
leridistim in these patients. IV. Compare the effect of leridistim vs filgrastim (G-CSF) on
the duration of thrombocytopenia, the incidence of infection, and the need for IV
antibiotics in these patients. V. Compare the effect of leridistim vs G-CSF on the number of
days of platelet and/or red blood cell transfusions in these patients.

OUTLINE: This is a dose escalation study of leridistim and then a randomized, open label,
multicenter study. Patients are randomized to one of two treatment arms. All patients
receive induction chemotherapy consisting of daunorubicin IV over 15-30 minutes on days 1-3
and cytarabine IV continuously on days 1-7. Patients who do not achieve aplasia after one
induction course may receive a second course. Dose Escalation Phase: Patients receive
leridistim subcutaneously (SQ) every other day beginning on day 11-14 and continuing for 42
days or until blood counts recover. Cohorts of 6 patients receive escalating doses of
leridistim until the maximum tolerated dose (MTD) or hematopoietically active dose (HAD) has
been determined. The MTD is defined as the dose prior to the dose level at which at least 2
of the same dose limiting toxicities occur in different patients. Consolidation Phase:
Patients then receive consolidation chemotherapy consisting of cytarabine IV over 1 hour
every 12 hours (patients 70 years and under) or every 24 hours (patients over 70 years) on
days 1-6. Beginning 24-48 hours after completion of consolidation chemotherapy, patients
receive leridistim as above. Randomized Phase: Eligible patients will receive induction and
consolidation chemotherapy as outlined above. Then patients are randomized to one of two
treatments. Arm I: Patients receive leridistim SQ every other day for up to 42 days or until
blood counts recover. Arm II: Patients receive filgrastim (G-CSF) SQ daily for up to 42 days
or until blood counts recover. Patients are followed at day 30 and then at 6 and 12 months.

PROJECTED ACCRUAL: A total of 86 patients (36 for phase I and 50 for phase II) will be
accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS: Induction phase: Cytologically proven de novo acute myeloid
leukemia (not M3) Eligible to receive cytarabine and daunorubicin Circulating blast count
no greater than 75,000/mL (hydroxyurea or leukapheresis allowed to decrease blast count)
No blast transformation of chronic myelogenous leukemia No myelodysplastic syndrome or
antecedent hematologic disorder longer than 6 months Post Induction Phase: Severe bone
marrow aplasia (less than 5% blasts and less than 10% cellularity) No persistent leukemia
after 2 induction courses

PATIENT CHARACTERISTICS: Age: 55 and over Performance status: Not specified Life
expectancy: Not specified Hematopoietic: See Disease Characteristics Hepatic: Bilirubin no
greater than 2.0 mg/dL Renal: Creatinine no greater than 2.0 mg/dL Cardiovascular: No
significant cardiac disease No cardiac arrhythmia No uncontrolled hypertension No recent
myocardial infarction or ischemia Other: No uncontrolled metabolic condition that would
preclude study No psychiatric condition that would preclude study HIV negative Hepatitis B
surface antigen negative No known hypersensitivity to corticosteroids, E. coli protein,
interleukin-3, SC-55494, SC-68420, leridistim, milodistim, or filgrastim (G-CSF)

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior interleukin-3, milodistim, SC-55494,
SC-68420, or leridistim No prior peripheral blood stem cell or bone marrow transplantation
No concurrent epoetin alfa or interleukin-11 Chemotherapy: See Disease Characteristics No
prior chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy
Surgery: At least 2 weeks since prior surgery (except catheter placement or biopsy) Other:
At least 3 weeks since prior investigational drug No other concurrent investigational drug

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Primary Purpose: Supportive Care

Principal Investigator

Mark Lawrence Heaney, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center

Authority:

United States: Federal Government

Study ID:

99-055

NCT ID:

NCT00004215

Start Date:

August 1999

Completion Date:

August 2000

Related Keywords:

  • Anemia
  • Leukemia
  • Neutropenia
  • Thrombocytopenia
  • untreated adult acute myeloid leukemia
  • adult acute erythroid leukemia (M6)
  • adult acute myeloblastic leukemia without maturation (M1)
  • adult acute myeloblastic leukemia with maturation (M2)
  • adult acute myelomonocytic leukemia (M4)
  • adult acute monoblastic leukemia (M5a)
  • adult acute megakaryoblastic leukemia (M7)
  • adult acute monocytic leukemia (M5b)
  • anemia
  • neutropenia
  • thrombocytopenia
  • adult acute minimally differentiated myeloid leukemia (M0)
  • Anemia
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Neutropenia
  • Thrombocytopenia

Name

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