Combination Chemotherapy in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome
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|ClinicalTrials.gov Identifier: NCT00002805|
Recruitment Status : Completed
First Posted : September 2, 2004
Last Update Posted : July 24, 2014
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|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||115 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Primary Completion Date :||May 2001|
|Study Completion Date :||June 2008|
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.
Other Names:Drug: cladribine
Other Names:Drug: cytarabine
Other Names:Drug: etoposide
Other Names:Drug: methotrexate
Other Names:Drug: mitoxantrone hydrochloride
Other Names:Drug: therapeutic hydrocortisone
Other Names: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
- Estimate second remission rate and survival rate [ Time Frame: 3 years ]
- Evaluate the mortality of the start of VP-16/Ara-C intensification [ Time Frame: 45 days ]
- Compare outcomes by the ethnicity and genderCompare outcomes by the ethnicity (and gender) in study CCG-2951, and will control for ethnicity in multivariate models comparing the treatment arms
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 ClinicalTrials.gov identifier (NCT number): NCT00002805
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|Study Chair:||Robert J. Wells, MD||Children's Hospital Medical Center, Cincinnati|