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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00002805
First received: November 1, 1999
Last updated: July 23, 2014
Last verified: July 2014
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Estimate second remission rate and survival rate [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Evaluate the mortality of the start of VP-16/Ara-C intensification [ Time Frame: 45 days ] [ Designated as safety issue: No ]
  • Compare outcomes by the ethnicity and gender [ Designated as safety issue: No ]
    Compare outcomes by the ethnicity (and gender) in study CCG-2951, and will control for ethnicity in multivariate models comparing the treatment arms


Enrollment: 115
Study Start Date: August 1997
Study Completion Date: June 2008
Primary Completion Date: May 2001 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00002805

  Show 38 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Robert J. Wells, MD Children's Hospital Medical Center, Cincinnati
  More Information

Additional Information:
No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00002805     History of Changes
Other Study ID Numbers: 2951, CCG-2951, CDR0000064907
Study First Received: November 1, 1999
Last Updated: July 23, 2014
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
recurrent childhood acute myeloid leukemia
secondary acute myeloid leukemia
childhood myelodysplastic syndromes

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Leukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Methotrexate
Cytarabine
Hydrocortisone-17-butyrate
Etoposide
Mitoxantrone
Cladribine
Hydrocortisone acetate
Hydrocortisone 17-butyrate 21-propionate
Cortisol succinate
Hydrocortisone
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on October 01, 2014