Clinical trial NCT00006265: Gemtuzumab Ozogamicin and High-Dose Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
Official title: A Dose Escalation And Phase II Study Of Gemtuzumab Ozogamicin (CMA-676; Mylotarg) With High-Dose Cytarabine For Patients With Refractory Or Relapsed Acute Myeloid Leukemia (AML)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Keywords: recurrent adult acute myeloid leukemia
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-09-03
Enrollment: 60
Sex: ALL
Minimum age (years): 17
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Monoclonal antibodies, such as gemtuzumab ozogamicin, can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as cytarabine, use different ways to stop cancer cells from dividing so they stop growing or die. Combining gemtuzumab ozogamicin with cytarabine may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combining gemtuzumab ozogamicin with high-dose cytarabine in treating patients who have relapsed or refractory acute myeloid leukemia.

Detailed description: OBJECTIVES:

* Determine the response rate in patients with relapsed or refractory acute myeloid leukemia treated with gemtuzumab ozogamicin (CMA-676) and high-dose cytarabine.
* Determine the safety and toxicity of this regimen in these patients.

OUTLINE: This is a dose-escalation study of gemtuzumab ozogamicin (CMA-676) (phase I closed to accrual effective 08/25/2003). Patients are stratified according to disease status (refractory vs relapsed).

* Phase I (closed to accrual effective 08/25/2003): Patients are enrolled in one of four cohorts.

  * Cohort I (closed to accrual as of 10/1/02): Patients receive CMA-676 at the first dose level IV over 2 hours on days 1 and 8.
  * Cohort IA (open to accrual as of 10/15/02): Patients receive high-dose cytarabine (HD-ARA-C) IV over 3 hours on days 1-5 and CMA-676 IV over 2 hours on day 7.
  * Cohort II: Patients receive HD-ARA-C as in cohort IA and CMA-676 at the first dose level IV over 2 hours on days 7 and 14.
  * Cohort IV: Patients receive CMA-676 at the second dose level and HD-ARA-C as in cohort II.

Dose escalation stops if at least 3 of 9 patients experience dose-limiting toxicity.

* Phase II: Patients receive HD-ARA-C IV over 3 hours on days 1-5 and CMA-676 IV over 2 hours on day 7 (one course).

Patients are followed at 1 month, monthly for 6 months, every 3 months for 2 years, and then annually for 10 years.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for phase I of the study and a total of 37 patients will be accrued for phase II of the study within 2 years. (Phase I closed to accrual effective 08/25/2003).

Eligibility criteria: DISEASE CHARACTERISTICS:

* One of the following diagnoses:

  * Primary refractory acute myeloid leukemia (AML)

    * More than 10% blasts in the bone marrow or blood after recovery from 2 courses of standard cytarabine- and anthracycline-based induction chemotherapy
    * No prior remission
  * Relapsed AML

    * More than 10% blasts in the bone marrow or blood after documented remission
    * Prior remission lasted more than 30 days
    * No prior treatment for current relapse
* CD33 expression on at least 20% of leukemia blast cells at initial diagnosis for primary refractory patients or at the time of relapse for all other patients
* No active CNS involvement

PATIENT CHARACTERISTICS:

Age:

* 17 and over

Performance status:

* 0-2

Life expectancy:

* Not specified

Hematopoietic:

* See Disease Characteristics
* WBC less than 30,000/mm\^3

Hepatic:

* Bilirubin less than 2.0 mg/dL
* No veno-occlusive disease of the liver
* No chronic liver disease unless due to AML

Renal:

* Not specified

Other:

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No active serious infection

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* At least 6 months since prior stem cell transplantation

Chemotherapy:

* See Disease Characteristics
* Prior etoposide and/or thioguanine during remission induction allowed
* Prior hydroxyurea for control of AML allowed
* At least 24 hours since prior hydroxyurea
* At least 3 months since prior high-dose cytarabine (greater than 2 g/m\^2/dose)-containing regimen
* No other concurrent chemotherapy

Endocrine therapy:

* Concurrent steroids for adrenal failure, hypersensitivity reactions, or septic shock allowed
* Concurrent ophthalmic corticosteroids allowed
* Concurrent hormones for nondisease-related conditions (e.g., insulin for diabetes or estrogens or progestins for gynecologic conditions) allowed

Radiotherapy:

* No concurrent radiotherapy

Surgery:

* Not specified

Other:

* More than 2 months since prior cytotoxic therapy

Primary outcomes:
measure: Complete remission rate
timeFrame: 8 or 14 days after tx initiation & 30 d post tx
Secondary outcomes:
measure: Toxicity
timeFrame: D 14, then 30, 60 , & 90 d post Tx, q 3 mon for 1 yr, then at relapse or death
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Northeast Alabama Regional Medical Center
state: Alabama
city: Birmingham
country: United States
facility: Veterans Affairs Medical Center - Birmingham
state: Alabama
city: La Jolla
country: United States
facility: Rebecca and John Moores UCSD Cancer Center
state: California
city: San Diego
country: United States
facility: Veterans Affairs Medical Center - San Diego
state: California
city: San Francisco
country: United States
facility: UCSF Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: Veterans Affairs Medical Center - San Francisco
state: California
city: Newark
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Washington
country: United States
facility: Lombardi Cancer Center at Georgetown University Medical Center
state: District of Columbia
city: Washington
country: United States
facility: Walter Reed Army Medical Center
state: District of Columbia
city: Washington
country: United States
facility: Veterans Affairs Medical Center - Washington, DC
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Broward General Medical Center
state: Florida
city: Hollywood
country: United States
facility: Memorial Regional Hospital Comprehensive Cancer Center
state: Florida
city: Miami Beach
country: United States
facility: CCOP - Mount Sinai Medical Center
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Cancer Institute
state: Florida
city: West Palm Beach
country: United States
facility: Palm Beach Cancer Institute
state: Florida
city: Chicago
country: United States
facility: Veterans Affairs Medical Center - Chicago (Westside Hospital)
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Chicago
country: United States
facility: Louis A. Weiss Memorial Hospital
state: Illinois
city: Peoria
country: United States
facility: CCOP - Illinois Oncology Research Association
state: Illinois
city: River Forest
country: United States
facility: West Suburban Center for Cancer Care
state: Illinois
city: Rockford
country: United States
facility: Saint Anthony Medical Center
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology, Incorporated
state: Indiana
city: Bettendorf
country: United States
facility: Hematology Oncology Associates of the Quad Cities
state: Iowa
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center at University of Iowa
state: Iowa
city: Louisville
country: United States
facility: Baptist Hospital East - Louisville
state: Kentucky
city: Baltimore
country: United States
facility: Marlene and Stewart Greenebaum Cancer Center, University of Maryland
state: Maryland
city: Boston
country: United States
facility: Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Memorial Medical Center - University Campus
state: Massachusetts
city: Saint Joseph
country: United States
facility: Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph
state: Michigan
city: Minneapolis
country: United States
facility: Veterans Affairs Medical Center - Minneapolis
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Cancer Center
state: Minnesota
city: Columbia
country: United States
facility: Veterans Affairs Medical Center - Columbia (Truman Memorial)
state: Missouri
city: Columbia
country: United States
facility: Ellis Fischel Cancer Center at University of Missouri - Columbia
state: Missouri
city: Kansas City
country: United States
facility: CCOP - Kansas City
state: Missouri
city: St. Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Omaha
country: United States
facility: UNMC Eppley Cancer Center at the University of Nebraska Medical Center
state: Nebraska
city: Las Vegas
country: United States
facility: CCOP - Southern Nevada Cancer Research Foundation
state: Nevada
city: Las Vegas
country: United States
facility: Veterans Affairs Medical Center - Las Vegas
state: Nevada
city: Hooksett
country: United States
facility: New Hampshire Oncology-Hematology, PA - Hooksett
state: New Hampshire
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center at Dartmouth Medical School
state: New Hampshire
city: Camden
country: United States
facility: Cooper University Hospital
state: New Jersey
city: Buffalo
country: United States
facility: Veterans Affairs Medical Center - Buffalo
state: New York
city: Elmhurst
country: United States
facility: Elmhurst Hospital Center
state: New York
city: Jamaica
country: United States
facility: Queens Cancer Center of Queens Hospital
state: New York
city: Manhasset
country: United States
facility: CCOP - North Shore University Hospital
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: New York Weill Cornell Cancer Center at Cornell University
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center, NY
state: New York
city: Syracuse
country: United States
facility: University Hospital at State University of New York - Upstate Medical University
state: New York
city: Syracuse
country: United States
facility: Veterans Affairs Medical Center - Syracuse
state: New York
city: Syracuse
country: United States
facility: CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.
state: New York
city: Asheville
country: United States
facility: Veterans Affairs Medical Center - Asheville
state: North Carolina
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
state: North Carolina
city: Concord
country: United States
facility: NorthEast Oncology Associates
state: North Carolina
city: Durham
country: United States
facility: Veterans Affairs Medical Center - Durham
state: North Carolina
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Fayetteville
country: United States
facility: Cape Fear Valley Health System
state: North Carolina
city: Kinston
country: United States
facility: Lenoir Memorial Hospital Cancer Center
state: North Carolina
city: Pinehurst
country: United States
facility: FirstHealth Moore Regional Hospital
state: North Carolina
city: Wilmington
country: United States
facility: New Hanover Regional Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: CCOP - Southeast Cancer Control Consortium
state: North Carolina
city: Winston-Salem
country: United States
facility: Comprehensive Cancer Center at Wake Forest University
state: North Carolina
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital - Ohio State University
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University Medical Center at University of Oklahoma Health Sciences Center
state: Oklahoma
city: Providence
country: United States
facility: Lifespan: The Miriam Hospital
state: Rhode Island
city: Memphis
country: United States
facility: University of Tennessee Cancer Institute
state: Tennessee
city: Memphis
country: United States
facility: Veterans Affairs Medical Center - Memphis
state: Tennessee
city: Dallas
country: United States
facility: Veterans Affairs Medical Center - Dallas
state: Texas
city: Bennington
country: United States
facility: Green Mountain Oncology Group
state: Vermont
city: Burlington
country: United States
facility: Vermont Cancer Center at University of Vermont
state: Vermont
city: White River Junction
country: United States
facility: Veterans Affairs Medical Center - White River Junction
state: Vermont
city: Charlottesville
country: United States
facility: Martha Jefferson Hospital
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates - Norfolk
state: Virginia
city: Richmond
country: United States
facility: MBCCOP - Massey Cancer Center
state: Virginia
city: Roanoke
country: United States
facility: Oncology and Hematology Associates of Southwest Virginia, Inc.
state: Virginia
city: Huntington
country: United States
facility: St. Mary's Medical Center
state: West Virginia
city: San Juan
country: Puerto Rico
facility: University of Puerto Rico School of Medicine Medical Sciences Campus
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Richard Stone, MD
role: STUDY_CHAIR
References:
citation: Stone RM, Moser B, Sanford B, Schulman P, Kolitz JE, Allen S, Stock W, Galinsky I, Vij R, Marcucci G, Hurd D, Larson RA; Cancer and Leukemia Group B. High dose cytarabine plus gemtuzumab ozogamicin for patients with relapsed or refractory acute myeloid leukemia: Cancer and Leukemia Group B study 19902. Leuk Res. 2011 Mar;35(3):329-33. doi: 10.1016/j.leukres.2010.07.017. Epub 2010 Aug 4.
citation: Stone RM, Moser B, Schulman P, et al.: A dose escalation and phase II study of gemtuzumab ozogamicin (GO) with high-dose cytarabine (HiDAC) for patients (pts) with refractory or relapsed acute myeloid leukemia (AML): CALGB 19902. [Abstract] Blood 104 (11): A-873, 2004.