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Combination Chemotherapy in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00002805
Recruitment Status : Completed
First Posted : September 2, 2004
Last Update Posted : July 24, 2014
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Brief Summary:

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy in treating patients with acute myeloid leukemia or myelodysplastic syndrome in first relapse or who did not achieve first remission.

Condition or disease Intervention/treatment Phase
Leukemia Biological: filgrastim Drug: cladribine Drug: cytarabine Drug: etoposide Drug: methotrexate Drug: mitoxantrone hydrochloride Drug: therapeutic hydrocortisone Procedure: allogeneic bone marrow transplantation Procedure: autologous bone marrow transplantation Procedure: peripheral blood stem cell transplantation Radiation: low-LET cobalt-60 gamma ray therapy Radiation: low-LET electron therapy Radiation: low-LET photon therapy Phase 2

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 115 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Acute Myeloid Leukemia Salvage Therapy for Patients in First Relapse or Who Fail to Achieve an Initial Remission or Who Develop AML as a Second Malignant Neoplasm
Study Start Date : August 1997
Actual Primary Completion Date : May 2001
Actual Study Completion Date : June 2008

Arm Intervention/treatment
Experimental: Treatment
Induction will consist of one course of cytarabine and mitoxantrone. Patients achieving a complete or partial response by the end of induction will start intensification. Intensification will consist of one course of chemotherapy (Cytarabine (Ara-C), Etoposide (VP-16), Filgrastim (G-CSF)). Patients who do not attain a CNS remission following the completion of intensification therapy, or who develop recurrence of CNS disease and have not previously received radiation therapy involving the central nervous system should receive craniospinal radiotherapy. Continuation Therapy: cladribine (2CdA), Etoposide.
Biological: filgrastim
Other Names:
  • G-CSF
  • Neupogen
  • NSC-614629

Drug: cladribine
Other Names:
  • Leustatin
  • 2CdA
  • 2-Chlorodeoxyadenosine

Drug: cytarabine
Other Names:
  • Ara-C
  • Cytosine Arabinoside
  • Cytosar-U

Drug: etoposide
Other Names:
  • VP-16
  • VePesid
  • NSC-141540

Drug: methotrexate
Other Names:
  • MTX
  • NSC-740

Drug: mitoxantrone hydrochloride
Other Names:
  • Novantrone
  • NSC-301739

Drug: therapeutic hydrocortisone
Other Names:
  • Hydrocortisone Sodium Succinate
  • NSC-10483

Procedure: allogeneic bone marrow transplantation
Procedure: autologous bone marrow transplantation
Procedure: peripheral blood stem cell transplantation
Radiation: low-LET cobalt-60 gamma ray therapy
Radiation: low-LET electron therapy
Radiation: low-LET photon therapy

Primary Outcome Measures :
  1. Estimate second remission rate and survival rate [ Time Frame: 3 years ]

Secondary Outcome Measures :
  1. Evaluate the mortality of the start of VP-16/Ara-C intensification [ Time Frame: 45 days ]
  2. Compare outcomes by the ethnicity and gender
    Compare outcomes by the ethnicity (and gender) in study CCG-2951, and will control for ethnicity in multivariate models comparing the treatment arms

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Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00002805

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Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
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Study Chair: Robert J. Wells, MD Children's Hospital Medical Center, Cincinnati

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Responsible Party: Children's Oncology Group Identifier: NCT00002805     History of Changes
Other Study ID Numbers: 2951
CDR0000064907 ( Other Identifier: Clinical )
First Posted: September 2, 2004    Key Record Dates
Last Update Posted: July 24, 2014
Last Verified: July 2014
Keywords provided by Children's Oncology Group:
recurrent childhood acute myeloid leukemia
secondary acute myeloid leukemia
childhood myelodysplastic syndromes
Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Hydrocortisone hemisuccinate
Etoposide phosphate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists