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A Phase II Randomized Trial of Immunologic and Chemotherapeutic Agents for Treatment of Patients With Relapsed or Refractory Acute Myelogenous Leukemia

Phase 2
18 Years
Not Enrolling

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Trial Information

A Phase II Randomized Trial of Immunologic and Chemotherapeutic Agents for Treatment of Patients With Relapsed or Refractory Acute Myelogenous Leukemia


- Compare the rates of complete response (CR) and CR without full platelet recovery in
patients with relapsed or refractory acute myelogenous leukemia treated with gemtuzumab
ozogamicin and cytarabine vs daunorubicin liposomal and cytarabine vs cyclophosphamide,
cytarabine, and topotecan.

- Compare the toxicities of these 3 regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified by disease status
(relapse less than 6 months after first complete response (CR) vs relapse 6-12 months after
first CR vs refractory to conventional initial induction chemotherapy (no more than 2
courses) or first reinduction (no more than 1 course) vs second or greater relapse).

- Induction: Patients are randomized to 1 of 3 treatment arms:

- Arm I: Patients receive cytarabine IV over 2 hours on days 1-4 and gemtuzumab
ozogamicin IV over 2 hours on day 5.

- Arm II: Patients receive daunorubicin liposomal IV over a minimum of 2 hours on
days 1-3 and cytarabine IV over 2 hours (beginning immediately after completion of
daunorubicin liposomal infusion) on days 1-4.

- Arm III: Patients receive cyclophosphamide IV over 1 hour every 12 hours on days
1-3, cytarabine IV over 2 hours (beginning immediately after completion of
cyclophosphamide infusion) on days 2-6, and topotecan IV continuously on days 2-6.

- Consolidation: Patients who achieve complete remission (CR) receive 1 additional course
of induction therapy on the same arm to which they were originally randomized beginning
within 4-6 weeks after initial documentation of CR. Patients on arm II receive no
additional daunorubicin liposomal if resting ejection fraction is less than 50%
preconsolidation. All patients receive sargramostim (GM-CSF) IV over 4 hours or SQ
daily beginning 24 hours after completion of consolidation therapy and continuing until
blood counts recover.

Patients are followed every 3 months through year 2, every 6 months through year 5, and then
annually thereafter until death.

PROJECTED ACCRUAL: A maximum of 150-165 patients (50-55 per arm) will be accrued for this
study within 2 years.

Inclusion Criteria


- Histologically proven acute myelogenous leukemia of one of the following types:

- Acute myeloblastic leukemia (FAB type M0, M1, or M2)

- Acute promyelocytic leukemia (FAB type M3) allowed if ineligible for an ECOG M3
protocol or if no tretinoin or arsenic trioxide therapy is planned

- Acute myelomonocytic leukemia (FAB type M4)

- Acute monocytic leukemia (FAB type M5)

- Acute erythroleukemia (FAB type M6)

- Acute megakaryocytic leukemia (FAB type M7)

- Must meet 1 of the following criteria:

- Relapse less than 6 months after first complete remission (CR)

- Relapse 6-12 months after first CR

- Refractory to conventional initial induction chemotherapy (no more than 2
courses) or first reinduction (no more than 1 course)

- Must have marrow documentation of residual leukemia after chemotherapy (for
at least 2 weeks duration)

- Second or greater relapse

- No relapse greater than 1 year after achieving first CR

- Blast cells must be CD33 positive

- Prior CNS leukemia allowed if there is currently documentation of no CNS involvement
on CSF examination (i.e., negative CSF by lumbar puncture)



- 18 and over

Performance status:

- ECOG 0-2

Life expectancy:

- Not specified


- See Disease Characteristics


- Bilirubin no greater than 2.0 mg/dL*

- SGOT less than 2 times upper limit of normal* NOTE: *Unless due to leukemia


- Creatinine no greater than 2.0 mg/dL


- See Chemotherapy

- No myocardial infarction within the past 3 months

- No significant congestive heart failure

- No significant cardiac arrhythmia

- Cardiac ejection fraction normal by MUGA scan or echocardiogram

- Resting ejection fraction at least 50% or at least 5% increase with exercise

- Shortening fraction at least 24% or normal by echocardiogram


- Not pregnant or nursing

- Fertile patients must use effective contraception

- No concurrent organ damage or other medical problems that would precludestudy therapy

- No concurrent evidence (including positive blood or deep tissue cultures or stains)
of invasive fungal infection

- No hypersensitivity to ingredients of gemtuzumab ozogamicin or daunorubicin liposomal

- No other active tumor that would interfere with study therapy or increase risk


Biologic therapy:

- No prior gemtuzumab ozogamicin


- See Disease Characteristics

- See Biologic therapy

- No prior daunorubicin liposomal or topotecan

- Prior doxorubicin (no greater than 300 mg/m2), daunorubicin (no greater than 300
mg/m2), idarubicin (no greater than 100 mg/m2), or mitoxantrone (no greater than 100
mg/m2) allowed if left ventricular function is adequate

- At least 4 weeks since prior chemotherapy except patients who are refractory to
conventional initial induction chemotherapy

- Prior hydroxyurea allowed within 4 weeks prior to beginning study

- Hydroxyurea must be discontinued at least 24 hours prior to beginning study

Endocrine therapy:

- Not specified


- At least 4 weeks since prior radiotherapy except patients who are refractory to
conventional initial induction chemotherapy


- Not specified

Type of Study:


Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Principal Investigator

Mark R. Litzow, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Mayo Clinic


United States: Federal Government

Study ID:




Start Date:

July 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 promyelocytic leukemia (M3)
  • adult acute myelomonocytic leukemia (M4)
  • adult acute monoblastic leukemia (M5a)
  • adult acute megakaryoblastic leukemia (M7)
  • adult acute monocytic leukemia (M5b)
  • adult acute minimally differentiated myeloid leukemia (M0)
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid



Albert Einstein Comprehensive Cancer Center Bronx, New York  10461
Mayo Clinic Cancer Center Rochester, Minnesota  55905
Stanford University Medical Center Stanford, California  94305-5408
H. Lee Moffitt Cancer Center and Research Institute Tampa, Florida  33612
Indiana University Cancer Center Indianapolis, Indiana  46202-5265
CCOP - Ann Arbor Regional Ann Arbor, Michigan  48106
University of Minnesota Cancer Center Minneapolis, Minnesota  55455
University of Rochester Cancer Center Rochester, New York  14642
Ireland Cancer Center Cleveland, Ohio  44106-5065
Kimmel Cancer Center of Thomas Jefferson University - Philadelphia Philadelphia, Pennsylvania  19107
University of Pennsylvania Cancer Center Philadelphia, Pennsylvania  19104
Fox Chase Cancer Center Philadelphia, Pennsylvania  19111
Robert H. Lurie Comprehensive Cancer Center, Northwestern University Chicago, Illinois  60611
CCOP - Missouri Valley Cancer Consortium Omaha, Nebraska  68131
CCOP - Southern Nevada Cancer Research Foundation Las Vegas, Nevada  89106
CCOP - Christiana Care Health Services Wilmington, Delaware  19899
CCOP - Colorado Cancer Research Program, Inc. Denver, Colorado  80209-5031
CCOP - Illinois Oncology Research Association Peoria, Illinois  61602
CCOP - Carle Cancer Center Urbana, Illinois  61801
Veterans Affairs Medical Center - Indianapolis (Roudebush) Indianapolis, Indiana  46202
CCOP - Iowa Oncology Research Association Des Moines, Iowa  50309-1016
Beth Israel Deaconess Medical Center Boston, Massachusetts  02215
New England Medical Center Hospital Boston, Massachusetts  02111
CCOP - Kalamazoo Kalamazoo, Michigan  49007-3731
CCOP - Metro-Minnesota Saint Louis Park, Minnesota  55416
Veterans Affairs Medical Center - East Orange East Orange, New Jersey  07018-1095
CCOP - Northern New Jersey Hackensack, New Jersey  07601
Hahnemann University Hospital Philadelphia, Pennsylvania  19102-1192
University of Pittsburgh Cancer Institute Pittsburgh, Pennsylvania  15213
CCOP - Duluth Duluth, Minnesota  55805
CCOP - Scottsdale Oncology Program Scottsdale, Arizona  85259-5404
CCOP - Cedar Rapids Oncology Project Cedar Rapids, Iowa  52403-1206
CCOP - Ochsner New Orleans, Louisiana  70121
CCOP - Merit Care Hospital Fargo, North Dakota  58122
CCOP - Toledo Community Hospital Oncology Program Toledo, Ohio  43623-3456
CCOP - Sioux Community Cancer Consortium Sioux Falls, South Dakota  57105-1080
Holden Comprehensive Cancer Center at The University of Iowa Iowa City, Iowa  52242-1009
NYU School of Medicine's Kaplan Comprehensive Cancer Center New York, New York  10016
CCOP - Central Illinois Springfield, Illinois  62526
CCOP - Columbus Columbus, Ohio  43206
CCOP - MainLine Health Wynnewood, Pennsylvania  19096
Veterans Affairs Medical Center - Madison Madison, Wisconsin  53705
University of Wisconsin Comprehensive Cancer Center Madison, Wisconsin  53792
CCOP - Evanston Evanston, Illinois  60201
Veterans Affairs Medical Center - Lakeside Chicago Chicago, Illinois  60611
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, Maryland  21231-2410
Veterans Affairs Medical Center - New York New York, New York  10010
CCOP - Marshfield Medical Research and Education Foundation Marshfield, Wisconsin  54449
Cleveland Clinic Taussig Cancer Center Cleveland, Ohio  44195
Cancer Center and Beckman Research Institute, City of Hope Duarte, California  91010-3000
MBCCOP - LSU Health Sciences Center New Orleans, Louisiana  70112
CCOP - Oklahoma Tulsa, Oklahoma  74136
Veterans Affairs Medical Center - Pittsburgh Pittsburgh, Pennsylvania  15240
Veterans Affairs Medical Center - Miami Miami, Florida  33125
Cancer Institute of New Jersey New Brunswick, New Jersey  08901
Veterans Affairs Medical Center - Minneapolis Minneapolis, Minnesota  55417
Veterans Affairs Medical Center - Palo Alto Palo Alto, California  94304
Veterans Affairs Medical Center - Brooklyn Brooklyn, New York  11209
Veterans Affairs Medical Center - Tampa (Haley) Tampa, Florida  33612
MBCCOP-Our Lady of Mercy Cancer Center Bronx, New York  10466
Veterans Affairs Medical Center - Gainsville Gainesville, Florida  32608-1197
Veterans Affairs Medical Center - Omaha Omaha, Nebraska  68105