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ACUTE MYELOID LEUKEMIA SALVAGE THERAPY FOR PATIENTS IN FIRST RELAPSE OR WHO FAIL TO ACHIEVE AN INITIAL REMISSION OR WHO DEVELOP ACUTE MYELOID LEUKEMIA AS A SECOND MALIGNANT NEOPLASM


Phase 2
N/A
21 Years
Not Enrolling
Both
Leukemia

Thank you

Trial Information

ACUTE MYELOID LEUKEMIA SALVAGE THERAPY FOR PATIENTS IN FIRST RELAPSE OR WHO FAIL TO ACHIEVE AN INITIAL REMISSION OR WHO DEVELOP ACUTE MYELOID LEUKEMIA AS A SECOND MALIGNANT NEOPLASM


OBJECTIVES: I. Determine the toxicity, remission rate, event-free survival, and overall
survival following induction with cytarabine/mitoxantrone (ARA-C/DHAD), intensification with
ARA-C and etoposide (VP-16), and consolidation with cladribine (2-CdA) and VP-16 in patients
with acute myeloid leukemia (AML) that is secondary, in first relapse, or has failed initial
remission induction therapy. II. Compare the remission induction rate and event-free
survival on this trial with prior second-line studies (i.e., protocols CCG-243, CCG-201, and
CCG-261P). III. Compare survival of patients on this trial with the survival of patients
relapsing or failing to achieve an initial complete remission (CR) on previous front-line
AML trials (i.e., protocols CCG-251, CCG-213, CCG-2861, and CCG-2891). IV. Determine the
frequency and prognostic significance of mdr1 gene expression and p53, topoisomerase II, and
deoxycytidine kinase gene mutations in these patients. V. Determine the disease-free and
overall survival of patients achieving a CR on this study in relation to the
post-intensification therapy received (i.e., bone marrow transplantation, chemotherapy, or
no further therapy). VI. Determine the frequency and degree of abnormal cardiac function on
echocardiogram or MUGA at 1 and 5 years in patients treated with mitoxantrone following
anthracycline therapy during initial treatment. VII. Provide a control arm evaluating the
safety of using phase I or II agents in an "upfront window" approach planned for future CCG
studies. VIII. Determine the toxicity, remission rate, event-free survival, and overall
survival in patients who fail to achieve a CR with ARA-C/DHAD induction and are then treated
with 2-CdA/VP-16. IX. Determine the biologic characteristics, toxicity, remission rate,
event-free survival, and overall survival following this treatment regimen in patients who
develop AML as a second malignancy.

OUTLINE: Patients who do not achieve M1/M2a marrow following Induction proceed to Salvage
Induction; all others proceed to Intensification. Patients receive Consolidation therapy on
Regimen A, B, or C according to the investigator's choice. The following acronyms are used:
ARA-C Cytarabine, NSC-63878 2-CdA Cladribine (2-Chlorodeoxyadenosine), NSC-105014 DHAD
Mitoxantrone, NSC-301739 G-CSF Filgrastim, NSC-614629 HC Hydrocortisone, NSC-10483 HD High
Dose MTX Methotrexate, NSC-740 PBSC Peripheral Blood Stem Cells TBI Total-Body Irradiation
TIT Triple Intrathecal Therapy (IT ARA-C/IT HC/IT MTX) VP-16 Etoposide, NSC-141540
INDUCTION: 2-Drug Combination Chemotherapy plus CNS Prophylaxis/Therapy. ARA-C/DHAD; G-CSF;
plus IT ARA-C and, if CNS disease at entry, TIT. SALVAGE INDUCTION: 2-Drug Combination
Chemotherapy. 2-CdA/VP-16. INTENSIFICATION: 2-Drug Combination Chemotherapy followed, as
indicated, by Radiotherapy. HD ARA-C/VP-16; followed, in patients with persistent CNS
disease, CNS relapse, or chloromas, by irradiation using megavoltage equipment (minimum Co60
and maximum 6 MV x-rays or electrons). CONSOLIDATION: Regimen A: 2-Drug Combination
Chemotherapy. 2-CdA/VP-16. Regimen B: Myeloablative Chemoradiotherapy followed by
Hematopoietic Rescue. TBI (equipment unspecified) with electron boosts to the testes, chest,
extramedullary sites, and, if indicated, craniospinal region; VP-16; followed by allogeneic
or autologous bone marrow or PBSC. Regimen C: No further therapy.

PROJECTED ACCRUAL: A total of 90 patients will be entered. The study may be closed if there
are 7 or more deaths in the first 45 patients who complete Intensification.

Inclusion Criteria


DISEASE CHARACTERISTICS: Acute myeloid leukemia (AML) or myelodysplastic syndrome in one
of the following categories: In first relapse Failed to achieve initial complete remission
Newly diagnosed secondary AML eligible Required bone marrow status: Greater than 25%
blasts (M3) OR Persistent abnormal clone on cytogenetics and 5-25% blasts (M2) No
Fanconi's anemia

PATIENT CHARACTERISTICS: Age: Under 22 Performance status: Not specified Hematopoietic:
See Disease Characteristics Hepatic: Bilirubin no greater than 1.5 times normal AST or ALT
less than 4.0 times normal Renal: Creatinine no greater than 1.5 times normal OR
Creatinine clearance or GFR greater than 70 mL/min per 1.73 square meters or GFR in
equivalent institutional normal range Cardiovascular: Shortening fraction greater than 27%
by echocardiogram or in institutional normal range OR Ejection fraction greater than 47%
by radionuclide angiogram

PRIOR CONCURRENT THERAPY: No more than 1 prior treatment No prior salvage therapy No prior
mitoxantrone

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Robert J. Wells, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Children's Hospital Medical Center, Cincinnati

Authority:

United States: Federal Government

Study ID:

CDR0000064907

NCT ID:

NCT00002805

Start Date:

August 1997

Completion Date:

Related Keywords:

  • Leukemia
  • recurrent childhood acute myeloid leukemia
  • secondary acute myeloid leukemia
  • childhood myelodysplastic syndromes
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Myelodysplastic Syndromes
  • Preleukemia

Name

Location

Fred Hutchinson Cancer Research CenterSeattle, Washington  98109
Memorial Sloan-Kettering Cancer CenterNew York, New York  10021
University of Texas - MD Anderson Cancer CenterHouston, Texas  77030-4009
University of Michigan Comprehensive Cancer CenterAnn Arbor, Michigan  48109-0752
Kaplan Cancer CenterNew York, New York  10016
Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania  19104
Mayo Clinic Cancer CenterRochester, Minnesota  55905
Jonsson Comprehensive Cancer Center, UCLALos Angeles, California  90095-1781
University of Chicago Cancer Research CenterChicago, Illinois  60637
Indiana University Cancer CenterIndianapolis, Indiana  46202-5265
University of Iowa Hospitals and ClinicsIowa City, Iowa  52242
University of Minnesota Cancer CenterMinneapolis, Minnesota  55455
Lineberger Comprehensive Cancer Center, UNCChapel Hill, North Carolina  27599-7295
Ireland Cancer CenterCleveland, Ohio  44106-5065
UCSF Cancer Center and Cancer Research InstituteSan Francisco, California  94115-0128
CCOP - KalamazooKalamazoo, Michigan  49007-3731
Vanderbilt Cancer CenterNashville, Tennessee  37232-6838
CCOP - Merit Care HospitalFargo, North Dakota  58122
Huntsman Cancer InstituteSalt Lake City, Utah  84112
University of Wisconsin Comprehensive Cancer CenterMadison, Wisconsin  53792
Herbert Irving Comprehensive Cancer CenterNew York, New York  10032
Veterans Affairs Medical Center - FargoFargo, North Dakota  58102
Cancer Institute of New JerseyNew Brunswick, New Jersey  08901
University of Nebraska Medical CenterOmaha, Nebraska  68198-3330
Long Beach Memorial Medical CenterLong Beach, California  90806
Children's Hospital Los AngelesLos Angeles, California  90027-0700
Children's Hospital of Orange CountyOrange, California  92668
Children's Hospital of DenverDenver, Colorado  80218
Children's National Medical CenterWashington, District of Columbia  20010-2970
Children's Hospital Medical Center - CincinnatiCincinnati, Ohio  45229-3039
Children's Hospital of ColumbusColumbus, Ohio  43205-2696
Doernbecher Children's HospitalPortland, Oregon  97201-3098
Children's Hospital of PittsburghPittsburgh, Pennsylvania  15213
Children's Mercy Hospital - Kansas CityKansas City, Missouri  64108
Children's Hospital and Medical Center - SeattleSeattle, Washington  98105