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Treatment of Newly Diagnosed Childhood Acute Myeloid Leukemia (AML) Using Intensive MRC-Based Therapy and Gemtuzumab Ozogamicin (GMTZ): A COG Pilot Study


Phase 2
N/A
N/A
Not Enrolling
Both
Leukemia

Thank you

Trial Information

Treatment of Newly Diagnosed Childhood Acute Myeloid Leukemia (AML) Using Intensive MRC-Based Therapy and Gemtuzumab Ozogamicin (GMTZ): A COG Pilot Study


OBJECTIVES:

Primary

- Determine the safety of gemtuzumab ozogamicin in children with newly diagnosed acute
myeloid leukemia undergoing intensive remission induction and intensification therapy.

- Determine the complete remission rate of patients treated with this regimen.

Secondary

- Determine the feasibility of performing biological studies (e.g., FLT3-ITD and MRD) for
risk group stratification in these patients.

- Determine the effect of karyotypic abnormalities on survival in patients treated with
this regimen.

OUTLINE: This is a multicenter study.

- Induction I: Patients receive high-dose cytarabine (ARA-C) IV twice daily on days 1-10;
daunorubicin IV over 6 hours on days 1, 3, and 5; etoposide IV over 4 hours on days
1-5; and gemtuzumab ozogamicin IV over 2 hours on day 6. Patients with CNS-negative
disease receive ARA-C intrathecally (IT) on day 1. Patients with CNS-positive disease
receive ARA-C IT twice weekly for 2-3 weeks. Between days 28-35, patients are
evaluated. Patients achieving remission or who have no more than 20% blasts proceed to
induction II.

- Induction II: Patients receive ARA-C IV twice daily on days 1-8; ARA-C IT on day 1; and
daunorubicin IV and etoposide IV as in induction I. Between days 28-35 patients are
evaluated. Patients achieving complete remission proceed to intensification course I.

- Intensification course I: Patients receive ARA-C IV over 1 hour twice daily on days
1-5; ARA-C IT as in induction II; and etoposide IV over 1 hour on days 1-5. Patients
are evaluated at day 28. Patients with a 5/6 or 6/6 matched family donor proceed to
allogeneic bone marrow transplantation. All other patients in complete remission
proceed to intensification course II.

- Intensification course II: Patients receive ARA-C IV over 2 hours twice daily on days
1-4; ARA-C IT as in induction II; mitoxantrone IV over 1 hour on days 3-6; and
gemtuzumab ozogamicin IV over 2 hours on day 7. Patients are evaluated on day 28 and
then proceed to intensification course III.

- Intensification course III: Patients receive ARA-C IV over 3 hours twice daily on days
1, 2, 8, and 9 and asparaginase intramuscularly on days 2 and 9.

- Allogeneic bone marrow transplantation: Patients receive a preparative regimen
comprising busulfan IV over 2 hours 4 times daily on days -9 to -6 and cyclophosphamide
IV over 1 hour once daily on days -5 to -2. Allogeneic stem cells are infused on day 0.

- Graft-versus-host disease prophylaxis: Patients receive oral or IV cyclosporine twice
daily on days -1 to 50 and methotrexate IV once daily on days 1, 3, 6, and 11.

In all courses, treatment continues in the absence of disease progression or unacceptable
toxicity.

Patients are followed monthly for 6 months, every 2 months for 6 months, every 4 months for
1 year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 330 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Newly diagnosed primary acute myeloid leukemia (AML)

- At least 20% bone marrow blasts

- Meets the customary FAB criteria for AML

- Patients with cytopenias and bone marrow blasts who do not meet the FAB
criteria are eligible provided they have a karyotypic abnormality
characteristic of de novo AML (e.g., t[8;21], inv16, or t[16;16]) OR they
have the unequivocal presence of megakaryoblasts

- Isolated granulocytic sarcoma (myeloblastoma) allowed regardless of the results
outlined above

- Previously untreated disease

- No promyelocytic leukemia (FAB M3)

- No documented myelodysplastic syndromes (preleukemia) (e.g., chronic myelomonocytic
leukemia, refractory anemia [RA], RA with excess blasts, or RA with ringed
sideroblasts)

- No juvenile myelomonocytic leukemia

- No Fanconi's anemia, Kostmann syndrome, Shwachman syndrome, or any other known bone
marrow failure syndrome

- No Down syndrome

PATIENT CHARACTERISTICS:

Age

- 1 month to 21 years* NOTE: *Children under 1 month of age who have progressive
disease are allowed

Performance status

- Karnofsky 50-100% (over 16 years of age) OR

- Lansky 50-100% (ages 1 to 16)* NOTE: Children under 1 year of age do not require a
performance status

Life expectancy

- Not specified

Hematopoietic

- Not specified

Hepatic

- No inadequate liver function

Renal

- No inadequate renal function

- No hyperuricemia (greater than 8.0 mg/dL)

- Creatinine clearance or radioisotope glomerular filtration rate (GFR) at least 70
mL/min OR an equivalent normal GFR OR

- Creatinine no greater than 1.5 times normal

Cardiovascular

- Shortening fraction at least 27% by echocardiogram OR

- Ejection fraction at least 50% by MUGA

Pulmonary

- No proven or suspected pneumonia

Other

- Not pregnant or nursing

- No proven or suspected sepsis or meningitis

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Not specified

Chemotherapy

- No prior chemotherapy except intrathecal cytarabine administered that was
administered at diagnosis

Endocrine therapy

- Prior topical and inhalation steroids allowed

- No concurrent steroids as antiemetics

Radiotherapy

- No prior radiotherapy

Surgery

- Not specified

Other

- No prior antileukemic therapy

- No concurrent pressor agent or ventilatory support unless approved by the study chair

- No concurrent participation in another COG therapeutic study

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety

Safety Issue:

Yes

Principal Investigator

Janet Franklin, MD, MPH

Investigator Role:

Study Chair

Investigator Affiliation:

Children's Hospital Los Angeles

Authority:

United States: Federal Government

Study ID:

CDR0000330133

NCT ID:

NCT00070174

Start Date:

December 2003

Completion Date:

Related Keywords:

  • Leukemia
  • untreated childhood acute myeloid leukemia and other myeloid malignancies
  • childhood acute monocytic leukemia (M5b)
  • childhood acute megakaryocytic leukemia (M7)
  • childhood acute minimally differentiated myeloid leukemia (M0)
  • childhood acute myeloblastic leukemia with maturation (M2)
  • childhood acute myeloblastic leukemia without maturation (M1)
  • childhood acute myelomonocytic leukemia (M4)
  • childhood acute monoblastic leukemia (M5a)
  • childhood acute erythroleukemia (M6)
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid

Name

Location

Roswell Park Cancer InstituteBuffalo, New York  14263
Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania  19104
Mayo Clinic Cancer CenterRochester, Minnesota  55905
Emory University Hospital - AtlantaAtlanta, Georgia  30322
University of Chicago Cancer Research CenterChicago, Illinois  60637
Indiana University Cancer CenterIndianapolis, Indiana  46202-5265
Barbara Ann Karmanos Cancer InstituteDetroit, Michigan  48201
University of Mississippi Medical CenterJackson, Mississippi  39216-4505
University of Texas Health Science Center at San AntonioSan Antonio, Texas  78284-7811
Midwest Children's Cancer CenterMilwaukee, Wisconsin  53226
CCOP - KalamazooKalamazoo, Michigan  49007-3731
Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health CenterFarmington, Connecticut  06360-2875
Van Elslander Cancer Center at St. John Hospital and Medical CenterGrosse Pointe Woods, Michigan  48236
CCOP - MeritCare HospitalFargo, North Dakota  58122
Geisinger Medical CenterDanville, Pennsylvania  17822-0001
Penn State Cancer Institute at Milton S. Hershey Medical CenterHershey, Pennsylvania  17033-0850
Vanderbilt-Ingram Cancer CenterNashville, Tennessee  37232-6838
Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical CenterLa Crosse, Wisconsin  54601
Comprehensive Cancer Center at Wake Forest UniversityWinston-Salem, North Carolina  27157-1082
Lutheran General Cancer Care CenterPark Ridge, Illinois  60068
Newark Beth Israel Medical CenterNewark, New Jersey  07112
New York Medical CollegeValhalla, New York  10595
St. Vincent HospitalGreen Bay, Wisconsin  54307-3508
University of Wisconsin Comprehensive Cancer CenterMadison, Wisconsin  53792
University of Miami Sylvester Comprehensive Cancer CenterMiami, Florida  33136
Holden Comprehensive Cancer Center at University of IowaIowa City, Iowa  52242-1002
Keesler Medical Center - Keesler Air Force BaseKeesler AFB, Mississippi  39534-2576
Siteman Cancer Center at Barnes-Jewish HospitalSaint Louis, Missouri  63110
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel HillChapel Hill, North Carolina  27599-7570
CCOP - Scott and White HospitalTemple, Texas  76508
Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimore, Maryland  21231-2410
Cancer Research Center of HawaiiHonolulu, Hawaii  96813
St. Barnabas Medical CenterLivingston, New Jersey  07039
Cleveland Clinic Taussig Cancer CenterCleveland, Ohio  44195
Madigan Army Medical CenterTacoma, Washington  98431-5048
Sutter Cancer CenterSacramento, California  95816
Hackensack University Medical CenterHackensack, New Jersey  07601
Children's Hospital Los AngelesLos Angeles, California  90027-0700
Children's Hospital of Orange CountyOrange, California  92668
Children's National Medical CenterWashington, District of Columbia  20010-2970
Children's Mercy HospitalKansas City, Missouri  64108
St. Joseph's Hospital and Medical CenterPaterson, New Jersey  07503
Children's Hospital of PittsburghPittsburgh, Pennsylvania  15213
Children's Hospital and Regional Medical Center - SeattleSeattle, Washington  98105
University of California Davis Cancer CenterSacramento, California  95817
Nemours Children's ClinicJacksonville, Florida  32207
Miami Children's HospitalMiami, Florida  33155-4069
All Children's HospitalSt. Petersburg, Florida  33701
Children's Memorial Hospital - ChicagoChicago, Illinois  60614
Wesley Medical CenterWichita, Kansas  67214
Maine Children's Cancer ProgramScarborough, Maine  04074-9308
Floating Hospital for ChildrenBoston, Massachusetts  02111
Cardinal Glennon Children's HospitalSaint Louis, Missouri  63104
University of New Mexico Cancer Research and Treatment CenterAlbuquerque, New Mexico  87131
Schneider Children's HospitalNew Hyde Park, New York  11042
St. Christopher's Hospital for ChildrenPhiladelphia, Pennsylvania  19134-1095
Driscoll Children's HospitalCorpus Christi, Texas  78466
Inova Fairfax HospitalFalls Church, Virginia  22042-3300
Fletcher Allen Health Care - University Health Center CampusBurlington, Vermont  05401
Phoenix Children's HospitalPhoenix, Arizona  85016-7710
Southern California Permanente Medical GroupDowney, California  90242
Children's Hospital Central CaliforniaMadera, California  93638-8762
Southern Illinois University School of MedicineSpringfield, Illinois  62794-9658
Kosair Children's HospitalLouisville, Kentucky  40202-3830
Children's Hospital of OmahaOmaha, Nebraska  68114
Sunrise Hospital and Medical CenterLas Vegas, Nevada  89109-2306
Brooklyn Hospital CenterBrooklyn, New York  11201
Maimonides Medical CenterBrooklyn, New York  11219
Children's Hospital Medical Center of AkronAkron, Ohio  44308
Children's Medical Center - DaytonDayton, Ohio  45404
Palmetto Health South Carolina Cancer CenterColumbia, South Carolina  29203
Texas Tech University Health Sciences Center School of MedicineAmarillo, Texas  79106
Children's Hospital of AustinAustin, Texas  78701
Covenant Children's HospitalLubbock, Texas  79410
Arkansas Cancer Research Center at University of Arkansas for Medical SciencesLittle Rock, Arkansas  72205
Markey Cancer Center at University of Kentucky Chandler Medical CenterLexington, Kentucky  40536-0084
Herbert Irving Comprehensive Cancer Center at Columbia UniversityNew York, New York  10032
Cancer Institute at Oregon Health and Science UniversityPortland, Oregon  97201-3098
Blumenthal Cancer Center at Carolinas Medical CenterCharlotte, North Carolina  28232-2861
Fairview University Medical Center - University CampusMinneapolis, Minnesota  55455
Winthrop University HospitalMineola, New York  11501
Oklahoma University Medical CenterOklahoma City, Oklahoma  73104
Sioux Valley Hospital and University of South Dakota Medical CenterSioux Falls, South Dakota  57117-5134
Comprehensive Cancer Center at University of Alabama at BirminghamBirmingham, Alabama  35294
Loma Linda University Cancer Institute at Loma Linda University Medical CenterLoma Linda, California  92354
Jonathan Jaques Children's Cancer Center at Miller Children's HospitalLong Beach, California  90801
Children's Hospital and Research Center - OaklandOakland, California  94609-1809
Kaiser Permanente Medical Center - OaklandSacramento, California  95825
Children's Hospital and Health Center - San DiegoSan Diego, California  92123-4282
Lee Cancer Care of Lee Memorial Health SystemFort Myers, Florida  33901
Broward General Medical Center Cancer CenterFt. Lauderdale, Florida  33316
University of Florida Shands Cancer CenterGainesville, Florida  32610-0232
Baptist-South Miami Regional Cancer ProgramMiami, Florida  33176
Florida Hospital Cancer Institute at Florida Hospital OrlandoOrlando, Florida  32803-1273
Sacred Heart Cancer Center at Sacred Heart HospitalPensacola, Florida  32504
St. Joseph's Cancer Institute at St. Joseph's HospitalTampa, Florida  33607
Kaplan Cancer Center at St. Mary's Medical CenterWest Palm Beach, Florida  33407
Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical CenterSavannah, Georgia  31403-3089
St. Luke's Mountain States Tumor Institute - BoiseBoise, Idaho  83712-6297
St. Vincent Indianapolis HospitalIndianapolis, Indiana  46260
Via Christi Cancer Center at Via Christi Regional Medical CenterWichita, Kansas  67214
CancerCare of Maine at Eastern Maine Medial CenterBangor, Maine  04401
Alvin and Lois Lapidus Cancer Institute at Sinai HospitalBaltimore, Maryland  21215
C.S. Mott Children's Hospital at University of MichiganAnn Arbor, Michigan  48109-0238
Spectrum Health Cancer Care - Butterworth CampusGrand Rapids, Michigan  49503-2560
Breslin Cancer Center at Ingham Regional Medical CenterLansing, Michigan  48910
Albert Einstein Cancer Center at Albert Einstein College of MedicineBronx, New York  10461
SUNY Upstate Medical University HospitalSyracuse, New York  13210
Mission Hospitals - Memorial CampusAsheville, North Carolina  28801
Presbyterian Cancer Center at Presbyterian HospitalCharlotte, North Carolina  28233-3549
Cincinnati Children's Hospital Medical CenterCincinnati, Ohio  45229-3039
Rainbow Babies and Children's HospitalCleveland, Ohio  44106-5000
Toledo HospitalToledo, Ohio  43606
Hollings Cancer Center at Medical University of South CarolinaCharleston, South Carolina  29425
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - DallasDallas, Texas  75390
Methodist Children's Hospital of South TexasSan Antonio, Texas  78229-3993
Primary Children's Medical CenterSalt Lake City, Utah  84113-1100
Massey Cancer Center at Virginia Commonwealth UniversityRichmond, Virginia  23298-0037
Carilion Cancer Center of Western VirginiaRoanoke, Virginia  24029
Providence Cancer Center at Sacred Heart Medical CenterSpokane, Washington  99220-2555
West Virginia University - Robert C. Byrd Health Sciences Center - Charleston DivisionCharleston, West Virginia  25302
Lombardi Cancer Center at Georgetown University Medical CenterWashington, District of Columbia  20007
Memorial Cancer Institute at Memorial Regional HospitalHollywood, Florida  33021
Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical CenterLos Angeles, California  90048-1865
Alfred I. duPont Hospital for ChildrenWilmington, Delaware  19803
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical SchoolNew Brunswick, New Jersey  08903
Mary Bridge Children's Hospital and Health Center - TacomaTacoma, Washington  98405
Cabell Huntington HospitalHuntington, West Virginia  25701
Children's Hospital Cancer CenterDenver, Colorado  80218
Children's Hospitals and Clinics - Minneapolis/St. PaulMinneapolis, Minnesota  55404
Leo W. Jenkins Cancer Center at Pitt County Memorial HospitalGreenville, North Carolina  27858-4354
Columbus Children's HospitalColumbus, Ohio  43205-2696
M.D. Anderson Cancer Center - OrlandoOrlando, Florida  32806
Medical College of Ohio Cancer InstituteToledo, Ohio  43614