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Phase III, Randomized, Multicenter Study to Assess the Efficacy and Safety of HuM195 (Recombinant Humanized Anti-CD33 Monoclonal Antibody) in Combination With Standardized Chemotherapy Compared to Standardized Chemotherapy Alone in the Treatment of Patients With Refractory or First-Relapsed Acute Myelogenous Leukemia (AML)


Phase 3
18 Years
N/A
Open (Enrolling)
Both
Leukemia

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Trial Information

Phase III, Randomized, Multicenter Study to Assess the Efficacy and Safety of HuM195 (Recombinant Humanized Anti-CD33 Monoclonal Antibody) in Combination With Standardized Chemotherapy Compared to Standardized Chemotherapy Alone in the Treatment of Patients With Refractory or First-Relapsed Acute Myelogenous Leukemia (AML)


OBJECTIVES: I. Compare the efficacy, safety, pharmacokinetics, and immunogenicity of
mitoxantrone, etoposide, and cytarabine (MEC) with or without monoclonal antibody HuG1-M195
in patients with refractory or relapsed acute myelogenous leukemia.

OUTLINE: This is a randomized, multicenter study. Patients are stratified by age (under 50
vs 50 and over) and duration of previous complete remission (CR) (0-6 vs 7-12 months). All
patients receive induction chemotherapy comprised of cytarabine IV over 2 hours,
mitoxantrone IV over a maximum of 20 minutes, and etoposide IV over 1-2 hours on days 1-6.
On day 5 of induction, patients are randomized to one of two treatment arms: Arm I: Patients
receive day 6 of induction chemotherapy. Patients then receive monoclonal antibody HuG1-M195
(MOAB HuM195) IV over 4 hours on days 6-9 or 7-10. Treatment with MOAB HuM195 repeats every
2 weeks for 2 courses (courses 1 and 2) in the absence of disease progression or
unacceptable toxicity. During course 1, MOAB HuM195 begins 30 minutes to 24 hours
postchemotherapy. Patients who do not achieve CR by day 70 of induction and show evidence of
bone marrow progression (regimen failure (RF)) are taken off study. Patients without RF are
assigned to one of two consolidation groups based on response: Group A (CR): Patients
receive consolidation chemotherapy comprised of mitoxantrone IV over a maximum of 20 minutes
on days 1 and 2, and cytarabine IV over 2 hours and etoposide IV over 1-2 hours on days 1-4.
Patients with New York Heart Association class II heart disease preconsolidation receive no
mitoxantrone during consolidation. Patients receive MOAB HuM195 IV over 4 hours on days 4-7
or 5-8. Treatment with MOAB HuM195 repeats every 2 weeks for 2 additional courses (courses 3
and 4). During course 3, MOAB HuM195 begins 30 minutes to 24 hours postchemotherapy. Group B
(partial remission (PR), hematologic improvement (HI), or stable disease (SD)): Patients
receive MOAB HuM195 as in group A but no consolidation chemotherapy. Patients without RF
after treatment on group A or B receive maintenance MOAB HuM195 IV over 4 hours on days 1-4.
Treatment repeats every month for 8 additional courses (courses 5-12). Arm II: Patients
receive day 6 of induction chemotherapy. Patients receive no MOAB HuM195 during the entire
study. Patients without RF at day 70 of induction are assigned to one of two consolidation
groups based on response: Group C (CR): Patients receive consolidation chemotherapy as in
group A. Group D (PR, HI, or SD): Patients receive no further treatment. Patients may be
eligible to receive MOAB HuM195 on PDL Study 195-302. Patients are followed every 3 months
for 1 year, and then every 6 months thereafter.

PROJECTED ACCRUAL: A maximum of 200 patients (100 per arm) will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS: Histologically proven acute myelogenous leukemia (AML) that may
have been primary AML, secondary AML, or preceded by hematologic disorder All FAB subtypes
except M3 Must meet one of the following three criteria: First relapse within 1 year after
documentation of a previous complete remission (CR) achieved by chemotherapy Refractory to
prior chemotherapy comprised of a minimum of 1 induction course, including cytarabine at a
minimum of 500 mg/m2 (e.g., 100 mg/m2/day for 5 days) plus an anthracycline No high dose
cytarabine (no cumulative dose greater than 3 g/m2) First relapse from a previous CR with
subsequent autologous bone marrow transplantation (BMT), only if all of the following
criteria are met: First BMT At least 100 days but less than 1 year posttransplantation At
least 25% cellularity of the bone marrow Previous BMT included full hematopoietic
recovery, defined by all of the following: Hemoglobin at least 10 g/dL (without
transfusion) Platelet count at least 100,000/mm3 (without transfusion) Absolute neutrophil
count at least 1,500/mm3 No transplantation candidates Bone marrow blasts (leukemic cells)
greater than 10% No chronic myelogenous leukemia in blast crisis No active CNS leukemia

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 50-100% Life
expectancy: Not specified Hematopoietic: See Disease Characteristics Hepatic: Bilirubin
less than 2.0 mg/dL (unless related to Gilbert's disease or due to leukemic infiltration)
SGOT or SGPT no greater than 4 times upper limit of normal (unless related to AML) Renal:
Creatinine less than 2.0 mg/dL (unless related to AML) Cardiovascular: Left ventricular
function normal No unstable cardiac arrhythmias, unstable angina pectoris, or myocardial
infarction within the past 6 months No New York Heart Association class III or IV heart
disease No electrocardiogram evidence of active ischemia Other: Not pregnant or nursing
Negative pregnancy test Fertile patients must use effective contraception during and for 1
month after study HIV negative No other active malignancy requiring therapy No active
serious infection that is uncontrolled by antimicrobial therapy Medically stable No
significant organ dysfunction

PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics At least 30 days
since prior experimental biologic therapy (e.g., interleukin-2) No concurrent biologic
therapy, including bone marrow transplantation Chemotherapy: See Disease Characteristics
For first relapse AML with recent or prior chemotherapy: Prior hydroxyurea given as a
short course (up to 48 hours) allowed, if needed, to reduce the peripheral leukocyte count
Hydroxyurea must be discontinued prior to study For refractory AML with recent or prior
chemotherapy: Greater than 2 weeks since prior chemotherapy except hydroxyurea given as
above No other concurrent chemotherapy Endocrine therapy: Not specified Radiotherapy: No
concurrent radiotherapy Surgery: Not specified Other: No other concurrent experimental
therapy Concurrent therapy for other preexisting diseases allowed

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Daniel Levitt, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

Facet Biotech

Authority:

United States: Federal Government

Study ID:

CDR0000068061

NCT ID:

NCT00006045

Start Date:

March 2000

Completion Date:

Related Keywords:

  • Leukemia
  • recurrent 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)
  • secondary acute myeloid leukemia
  • adult acute monocytic leukemia (M5b)
  • adult acute minimally differentiated myeloid leukemia (M0)
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid

Name

Location

Roswell Park Cancer InstituteBuffalo, New York  14263
Memorial Sloan-Kettering Cancer CenterNew York, New York  10021
Albert Einstein Comprehensive Cancer CenterBronx, New York  10461
Jonsson Comprehensive Cancer Center, UCLALos Angeles, California  90095-1781
USC/Norris Comprehensive Cancer CenterLos Angeles, California  90033-0800
University of Iowa Hospitals and ClinicsIowa City, Iowa  52242
Johns Hopkins Oncology CenterBaltimore, Maryland  21287
Lineberger Comprehensive Cancer Center, UNCChapel Hill, North Carolina  27599-7295
Duke Comprehensive Cancer CenterDurham, North Carolina  27710
Ireland Cancer CenterCleveland, Ohio  44106-5065
Milton S. Hershey Medical CenterHershey, Pennsylvania  17033
University of Pennsylvania Cancer CenterPhiladelphia, Pennsylvania  19104
Beth Israel Deaconess Medical CenterBoston, Massachusetts  02215
New England Medical Center HospitalBoston, Massachusetts  02111
West Michigan Cancer CenterKalamazoo, Michigan  49007-3731
Loyola University Medical CenterMaywood, Illinois  60153
Massachusetts General Hospital Cancer CenterBoston, Massachusetts  02114
New York Presbyterian Hospital - Cornell CampusNew York, New York  10021
Medical College of WisconsinMilwaukee, Wisconsin  53226
Beckman Research Institute, City of HopeLos Angeles, California  91010
New York Medical CollegeValhalla, New York  10595
Akron General Medical CenterAkron, Ohio  44302
Dana-Farber Cancer InstituteBoston, Massachusetts  02115
North Shore University HospitalManhasset, New York  11030
Cleveland Clinic Taussig Cancer CenterCleveland, Ohio  44195
Sutter Cancer CenterSacramento, California  95816
Cancer Institute of New JerseyNew Brunswick, New Jersey  08901
University of California Davis Cancer CenterSacramento, California  95817
St. Joseph Hospital - OrangeOrange, California  92868
University of Illinois at ChicagoChicago, Illinois  60612
Sidney Kimmel Cancer CenterSan Diego, California  92121
Washington University Barnard Cancer CenterSaint Louis, Missouri  63110
Louisiana State University School of MedicineNew Orleans, Louisiana  70112-2822
Nevada Cancer CenterLas Vegas, Nevada  89109
Emory ClinicAtlanta, Georgia  30365
Vanderbilt University Medical CenterNashville, Tennessee  37232-2516
University of Pittsburgh Medical CenterPittsburgh, Pennsylvania  15213
Washington Cancer InstituteWashington, District of Columbia  20010
West Clinic, P.C.Memphis, Tennessee  38117
North Mississippi Hematology and Oncology Associates, Ltd.Tupelo, Mississippi  38801