Phase II Study of IFN-A plus Low-Dose ARA-C in Previously Untreated Patients with Philadelphia Chromosome Positive CML (Summary Last Modified 01/92)
Basic Trial Information
|Phase II||Treatment||Completed||over 18||NCI||CLB-9013|
I. Determine whether the combination of low-dose cytarabine and interferon alpha can reduce or eliminate Philadelphia chromosome-positive cells in previously untreated patients with chronic phase CML. II. Assess the response rate, duration of response, and survival of patients with chronic phase CML treated with this regimen. III. Define the safety and toxicities of this treatment for CML patients. IV. Assess the proposed new guidelines for clearly defining chronic phase CML by comparing the outcome of patients in blast crisis with those having aggressive disease (as defined by Karanas and Silver and Gralnick and Bennett). V. Determine, in conjunction with protocol CLB-8761, whether quantitative measurements of the breakpoint cluster region (bcr) test are comparable to cytogenetic analysis and correlate with clinical parameters in the management of patients on this treatment regimen. VI. Determine, in conjunction with protocol CLB-8761 and in a large-sample prospective manner, whether the location of the chromosome 22 breakpoint within the bcr, as determined by fine gene mapping, accounts for variability in disease duration. VII. Investigate, in conjunction with protocol CLB-8761, the concordance of Ph(-) and Ph(+) cells between blood and bone marrow as remission is achieved on this regimen.
Chronic phase CML with diagnosis established by all of the following: Unexplained peripheral blood leukocytosis Myeloid hyperplasia and less than 20% myeloblasts plus promyelocytes on bone marrow aspirate Philadelphia chromosome positive (banded, bone marrow cytogenetic studies required in all patients) Concurrent registration on protocol CLB-8761 (molecular genetics of CML) required
Biologic therapy: No prior interferon Chemotherapy: No prior chemotherapy, including hydroxyurea Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy Surgery: More than 4 weeks since major surgery More than 2 weeks since minor surgery
Age: Over 18 Performance status: CALGB 0-2 Life expectancy: At least 2 years Hematopoietic: Platelets greater than 100,000 Hepatic: Bilirubin less than 1.5 x normal SGOT/SGPT less than 1.5 x normal Alkaline phosphatase less than 1.5 x normal (unless elevation presumed due to CML) PT/PTT less than 1.5 x normal Renal: Creatinine less than 1.8 mg/dl Cardiovascular: No significant cardiovascular risk history, e.g.: No NYHA class III/IV No myocardial infarction within 1 year No ventricular arrhythmias (except PVCs) Other: No other serious medical or psychiatric illness that would prevent informed consent or require therapy No second malignancy within 5 years except: Inactive nonmelanomatous skin cancer In situ cervical cancer No pregnant women Effective contraception required while on protocol
80 patients will be entered to provide 75 evaluable patients.
Nonrandomized study. Single-agent Chemotherapy plus Biological Response Modifier Therapy. Cytarabine, ARA-C, NSC-63878; plus Interferon alpha-2b (Schering), IFN-A, NSC-377523.
Farag SS, Ruppert AS, Mrózek K, et al.: Prognostic significance of additional cytogenetic abnormalities in newly diagnosed patients with Philadelphia chromosome-positive chronic myelogenous leukemia treated with interferon-alpha: a Cancer and Leukemia Group B study. Int J Oncol 25 (1): 143-51, 2004.[PUBMED Abstract]
Silver RT, Peterson BL, Szatrowski TP, et al.: Treatment of the chronic phase of chronic myeloid leukemia with an intermittent schedule of recombinant interferon alfa-2b and cytarabine: results from CALGB study 9013. Leuk Lymphoma 44 (1): 39-48, 2003.[PUBMED Abstract]
Silver RT, Peterson BL, Szatrowski TP, et al.: Treatment of chronic myeloid leukemia (CML) with an intermittent schedule of interferon α-B. [Abstract] Proceedings of the American Society of Clinical Oncology 20: A-1222, 2001.
Hensley ML, Peterson B, Silver RT, et al.: Risk factors for severe neuropsychiatric toxicity in patients receiving interferon alfa-2b and low-dose cytarabine for chronic myelogenous leukemia: analysis of Cancer and Leukemia Group B 9013. J Clin Oncol 18 (6): 1301-8, 2000.[PUBMED Abstract]
Hensley ML, Silver RT, Peterson BL, et al.: Risk factors for severe neuropsychiatric toxicity (NPtox) in patients receiving interferon-alfa-2b (rIFN-a) and low-dose cytarabine (AraC) for chronic myeloid leukemia (CML): analysis of CALGB 9013. [Abstract] Proceedings of the American Society of Clinical Oncology 18: A1604, 1999.
Trial Contact Information
Trial Lead Organizations
Cancer and Leukemia Group B
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.