S0333 Combination Chemotherapy in Treating Patients With Newly Diagnosed Acute Lymphoblastic Leukemia
Overview[ - collapse ][ - ]
| Purpose | RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy), and giving the drugs in different combinations may kill more cancer cells. PURPOSE: This phase II trial is studying how well combination chemotherapy works in treating patients with newly diagnosed acute lymphoblastic leukemia. |
|---|---|
| Condition | Leukemia |
| Intervention | Biological: filgrastim Drug: cyclophosphamide Drug: cytarabine Drug: daunorubicin Drug: dexamethasone Drug: doxorubicin Drug: leucovorin Drug: mercaptopurine Drug: methotrexate Drug: mitoxantrone Drug: Asparaginase Drug: prednisone Drug: thioguanine Drug: vincristine Radiation: radiation therapy Drug: allopurinol Drug: bactrim |
| Phase | Phase 2 |
| Sponsor | Southwest Oncology Group |
| Responsible Party | Southwest Oncology Group |
| ClinicalTrials.gov Identifier | NCT00109837 |
| First Received | May 3, 2005 |
| Last Updated | February 28, 2014 |
| Last verified | February 2014 |
Tracking Information[ + expand ][ + ]
| First Received Date | May 3, 2005 |
|---|---|
| Last Updated Date | February 28, 2014 |
| Start Date | April 2005 |
| Estimated Primary Completion Date | November 2014 |
| Current Primary Outcome Measures | Continuous Complete Remission at 1 Year [Time Frame: After induction, after consolidation, every 3 months during maintenance, and every three months after off treatment for up to a year] [Designated as safety issue: No]A patient has a continuous complete remission at 1 year if they achieve a CR and are alive 365 days after registering to the study. |
| Current Secondary Outcome Measures | Toxicity [Time Frame: Patients were assessed for adverse events after the induction cycle] [Designated as safety issue: Yes]Number of patients with Grade 3-5 adverse events that are related to study drug by given type of adverse event |
Descriptive Information[ + expand ][ + ]
| Brief Title | S0333 Combination Chemotherapy in Treating Patients With Newly Diagnosed Acute Lymphoblastic Leukemia |
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| Official Title | A Phase II Study of Double Induction Chemotherapy for Newly Diagnosed Non-L3 Adult Acute Lymphoblastic Leukemia With Investigation of Minimal Residual Disease and Risk of Relapse Following Maintenance Chemotherapy |
| Brief Summary | RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy), and giving the drugs in different combinations may kill more cancer cells. PURPOSE: This phase II trial is studying how well combination chemotherapy works in treating patients with newly diagnosed acute lymphoblastic leukemia. |
| Detailed Description | OBJECTIVES: Primary - Determine the probability of 1-year continuous complete remission in patients with newly diagnosed acute lymphoblastic leukemia treated with first induction chemotherapy comprising daunorubicin, vincristine, prednisone, and pegaspargase; and second induction chemotherapy comprising high-dose cytarabine and mitoxantrone. Secondary - Determine the frequency and severity of toxic effects of these induction regimens followed by consolidation therapy comprising cyclophosphamide, cytarabine, mercaptopurine, and methotrexate and maintenance chemotherapy comprising mercaptopurine, methotrexate, vincristine, doxorubicin, dexamethasone, cyclophosphamide, thioguanine, and cytarabine in these patients. Other objectives (if funding allows): - To evaluate in a preliminary manner the significance of detecting minimal residual disease as a prognostic factor for survival and relapse-free survival of patients receiving chemotherapy - To evaluate in a preliminary manner the pattern of gene expression of patients entered onto the trial and its relationship to cytogenetics/FISH risk classification, overall survival, and relapse-free survival OUTLINE: This is a multicenter study. - First induction chemotherapy: Patients receive daunorubicin IV on days 1-3; vincristine IV on days 1, 8, 15, and 22; prednisone IV or orally on days 1-28, followed by a taper to day 35; and pegaspargase IV or subcutaneously (SC) on day 15. Patients with CNS leukemia also receive methotrexate intrathecally (IT) or intraventricularly twice weekly and oral leucovorin calcium four times daily for 4 doses after each administration of methotrexate. When blasts are no longer present in the spinal fluid, patients receive methotrexate IT or intraventricularly once weekly for 4 weeks and then once monthly for 1 year. Patients are reevaluated on day 28. Patients who achieve A1 bone marrow status and B1 peripheral blood status or those with resistant disease proceed to second induction therapy. - Second induction chemotherapy: Patients receive high-dose cytarabine IV on days 1-5; mitoxantrone IV on day 3; and filgrastim (G-CSF) SC or IV beginning on day 7 and continuing until blood counts recover. Patients with CNS leukemia also receive methotrexate and leucovorin calcium as in first induction chemotherapy. Patients are reevaluated on day 28. Patients who achieve A1 bone marrow status and B1 peripheral blood status with no extramedullary disease (other than CNS involvement) proceed to consolidation chemotherapy. Patients with resistant disease OR Philadelphia chromosome- or BCR/ABL-positive disease are removed from the study after receiving double induction chemotherapy. - Consolidation chemotherapy: Patients receive cyclophosphamide IV on days 1, 15, and 29; cytarabine IV on days 2-5 and 16-19; oral mercaptopurine on days 1-28; and methotrexate IT or intraventricularly on days 2, 9, 16, and 23. Patients with CNS leukemia also undergo cranial radiotherapy once daily, 5 days a week, for 2 weeks. Patients in complete remission proceed to maintenance chemotherapy. - Maintenance chemotherapy: - Course 1: Patients receive oral mercaptopurine on days 1-63 and oral methotrexate on days 1, 8, 15, 22, 29, 36, 43, 50, and 57. Patients proceed to course 2 after blood counts recover. - Course 2: Patients receive vincristine IV and doxorubicin IV on days 1, 8, 15, and 22 and oral dexamethasone on days 1-28. Patients proceed to course 3 after blood counts recover. - Course 3: Patients receive cyclophosphamide IV on day 1; oral thioguanine on days 1-14; and cytarabine IV on days 3-6 and 10-13. Patients proceed to course 4 after blood counts recover. - Course 4: Patients receive oral mercaptopurine once daily for 2 years and oral methotrexate once weekly for 2 years. Treatment continues in the absence of disease relapse or unacceptable toxicity. After completion of study therapy, patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually for 3 years. |
| Study Type | Interventional |
| Study Phase | Phase 2 |
| Study Design | Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment |
| Condition | Leukemia |
| Intervention | Biological: filgrastim As needed per physician discretion Drug: cyclophosphamide Cyclophosphamide Consolidation: 650 mg/m2; IV; days 1, 15, 29 Post-consolidation course 3: 650 mg/m2; IV; day 1 Drug: cytarabine Induction 2: 3 g/m2; IV over 3 hrs; days 1-5 Consolidation: 75 mg/m2/d; IV push; days 2-5 and 16-19 Post-consolidation course 3: 75 mg/m2/d; IV push; days 3-6 and 10-13 Drug: daunorubicin Induction: 60 mg/m2/d; IV; days 1, 2, and 3 Drug: dexamethasone Induction 2: 0.1% QID; eye drops; days 1-6 Post consolidation course 2: 10 mg/m2/d; PO; days 1-28 Drug: doxorubicin Post consolidation: 25 mg/m2; IV; days 1, 8, 15, and 22 Drug: leucovorin For CNS during induction: 5 mg every 6 hrs for 4 doses; PO; days 1, 4, 8, 11, etx.; after methotrexate if WBC < 3,000 Drug: mercaptopurine Consolidation: 60 mg/m2; PO; days 1-28 Post-consolidation course 1: 60 mg/m2/d; PO; days 1-63 Post-consolidation course 4: 60 mg/m2/d; PO; daily for 2 yrs Drug: methotrexate Consolidation: 12 mg; intrathecal or intraventricularly; days 2, 9, 16, and 23 Post-consolidation course 1: 20 mg/m2/wk; PO; days 1, 8 15, 22, 29, 36, 43, 50, 57 Post-consolidation course 4: 20 mg/m2; PO; weekly for 2 yrs Drug: mitoxantrone Induction 2: 80 mg/m2; IV; day 3 Drug: Asparaginase Induction: 2,000 IU/m2; IM or IV; day 15 Drug: prednisone Induction: 60 mg/m2/d; PO or IV; days 1-35 Drug: thioguanine Post-consolidation course 3: 60 mg/m2/d; PO; days 1-14 Drug: vincristine Induction: 1.4 mg/m2/d (2 mg max); IV; days 1, 8, 15, 22 Radiation: radiation therapy For CNS during consolidation: cranial radiation after blasts are no longer present in spinal fluid. Total dose of 1800 cGy over 2 wks in 10 fractions of 180 cGy 5 days/wk. Drug: allopurinol 300 mg/d PO Days 1-7 Drug: bactrim 1 double strenth tablet 2x/d, 2x/wk, PO, begin with prednisone |
| Study Arm (s) | Experimental: Induc x2, Consol, Maint Induc 1: Allopurinol; Daunorubicin; Vincristine; Prednisone; asparaginase; Bactrim Induc 2: Allopurinol; cytarabine; Dexamethasone; filgrastim; mitoxantrone; Methotrexate; leucovorin Consol: Cyclophosphamide; cytarabine; 6-mercaptopurine; Methotrexate; filgrastim Maint:Course 1: 6-mercaptopurine; Methotrexate Course 2: Vincristine; doxorubicin; Dexamethasone Course 3: Cyclophosphamidee; thioguanine; cytarabine Course 4: 6-mercaptopurine; methotrexate |
Recruitment Information[ + expand ][ + ]
| Recruitment Status | Active, not recruiting |
|---|---|
| Estimated Enrollment | 79 |
| Estimated Completion Date | November 2014 |
| Estimated Primary Completion Date | November 2010 |
| Eligibility Criteria | DISEASE CHARACTERISTICS: - Morphologically confirmed acute lymphoblastic leukemia (ALL), meeting any of the following criteria: - FAB class L1 or L2 disease - Mixed lineage ALL - Ph-negative/BCR/ABL-negative - Newly diagnosed disease - Patients with the following diagnoses are not eligible: - FAB class L3 ALL - Non-Hodgkin's lymphoma - Chronic myelogenous leukemia in lymphoid blast crisis - Mixed lineage acute myeloid leukemia - Acute minimally differentiated myeloid leukemia (M0) - Must be registered on protocols SWOG-9007 AND SWOG-S9910 PATIENT CHARACTERISTICS: Age - 18 to 64 Performance status - Zubrod 0-3 Life expectancy - Not specified Hematopoietic - Not specified Hepatic - No chronic liver disease - Hepatitis panel, including hepatitis B and C, negative - History of hepatitis A with positive antibody allowed Renal - Creatinine ≤ 1.5 times upper limit of normal OR - Creatinine clearance > 60 mL/min Cardiovascular - Left ventricular function normal - Ejection fraction ≥ 50% by MUGA or 2-dimensional echocardiogram - No symptomatic congestive heart failure - No coronary artery disease - No cardiomyopathy - No uncontrolled arrhythmia Other - Not pregnant or nursing - Fertile patients must use effective contraception - HIV negative - No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer in complete remission PRIOR CONCURRENT THERAPY: Biologic therapy - Not specified Chemotherapy - No prior remission induction chemotherapy for ALL - Prior hydroxyurea to control WBC count allowed Endocrine therapy - Not specified Radiotherapy - Not specified Surgery - Not specified Other - No other prior treatment for ALL |
| Gender | Both |
| Ages | 18 Years |
| Accepts Healthy Volunteers | No |
| Contacts | Not Provided |
| Location Countries | United States |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT00109837 |
|---|---|
| Other Study ID Numbers | CDR0000426447 |
| Has Data Monitoring Committee | Yes |
| Information Provided By | Southwest Oncology Group |
| Study Sponsor | Southwest Oncology Group |
| Collaborators | National Cancer Institute (NCI) |
| Investigators | Study Chair: Jerry Radich, MD Fred Hutchinson Cancer Research CenterPrincipal Investigator: Frederick R. Appelbaum, MD Fred Hutchinson Cancer Research Center |
| Verification Date | February 2014 |
Locations[ + expand ][ + ]
| Providence Saint Joseph Medical Center - Burbank | Burbank, California, United States, 91505 |
|---|---|
| Cardinal Bernardin Cancer Center at Loyola University Medical Center | Maywood, Illinois, United States, 60153 |
| Cancer Center of Kansas, PA - Chanute | Chanute, Kansas, United States, 66720 |
| Cancer Center of Kansas, PA - Dodge City | Dodge City, Kansas, United States, 67801 |
| Cancer Center of Kansas, PA - El Dorado | El Dorado, Kansas, United States, 67042 |
| Cancer Center of Kansas-Independence | Independence, Kansas, United States, 67301 |
| Cancer Center of Kansas, PA - Kingman | Kingman, Kansas, United States, 67068 |
| Lawrence Memorial Hospital | Lawrence, Kansas, United States, 66044 |
| Southwest Medical Center | Liberal, Kansas, United States, 67901 |
| Cancer Center of Kansas, PA - Newton | Newton, Kansas, United States, 67114 |
| Menorah Medical Center | Overland Park, Kansas, United States, 66209 |
| Cancer Center of Kansas, PA - Parsons | Parsons, Kansas, United States, 67357 |
| Cancer Center of Kansas, PA - Pratt | Pratt, Kansas, United States, 67124 |
| Cancer Center of Kansas, PA - Salina | Salina, Kansas, United States, 67042 |
| Shawnee Mission Medical Center | Shawnee Mission, Kansas, United States, 66204 |
| Cancer Center of Kansas, PA - Wellington | Wellington, Kansas, United States, 67152 |
| Cancer Center of Kansas, PA - Medical Arts Tower | Wichita, Kansas, United States, 67208 |
| CCOP - Wichita | Wichita, Kansas, United States, 67214 |
| Cancer Center of Kansas, PA - Wichita | Wichita, Kansas, United States, 67214 |
| Associates in Womens Health, PA - North Review | Wichita, Kansas, United States, 67208 |
| Via Christi Cancer Center at Via Christi Regional Medical Center | Wichita, Kansas, United States, 67214 |
| Wesley Medical Center | Wichita, Kansas, United States, 67214 |
| Cancer Center of Kansas, PA - Winfield | Winfield, Kansas, United States, 67156 |
| University of Michigan Comprehensive Cancer Center | Ann Arbor, Michigan, United States, 48109-0942 |
| Josephine Ford Cancer Center at Henry Ford Hospital | Detroit, Michigan, United States, 48202 |
| Independence Regional Health Center | Independence, Missouri, United States, 64050 |
| CCOP - Kansas City | Kansas City, Missouri, United States, 64131 |
| Parvin Radiation Oncology | Kansas City, Missouri, United States, 64116 |
| North Kansas City Hospital | Kansas City, Missouri, United States, 64116 |
| Truman Medical Center - Hospital Hill | Kansas City, Missouri, United States, 64108 |
| Research Medical Center | Kansas City, Missouri, United States, 64132 |
| St. Joseph Medical Center | Kansas City, Missouri, United States, 64114 |
| Saint Luke's Cancer Institute at Saint Luke's Hospital | Kansas City, Missouri, United States, 64111 |
| Saint Luke's East - Lee's Summit | Lee's Summit, Missouri, United States, 64086 |
| Liberty Hospital | Liberty, Missouri, United States, 64068 |
| Heartland Regional Medical Center | Saint Joseph, Missouri, United States, 64506 |
| CCOP - Montana Cancer Consortium | Billings, Montana, United States, 59101 |
| Billings Clinic - Downtown | Billings, Montana, United States, 59107-7000 |
| St. Vincent Healthcare Cancer Care Services | Billings, Montana, United States, 59101 |
| Northern Rockies Radiation Oncology Center | Billings, Montana, United States, 59101 |
| Hematology-Oncology Centers of the Northern Rockies - Billings | Billings, Montana, United States, 59101 |
| Bozeman Deaconess Cancer Center | Bozeman, Montana, United States, 59715 |
| St. James Healthcare Cancer Care | Butte, Montana, United States, 59701 |
| Great Falls Clinic - Main Facility | Great Falls, Montana, United States, 59405 |
| Sletten Cancer Institute at Benefis Healthcare | Great Falls, Montana, United States, 59405 |
| Big Sky Oncology | Great Falls, Montana, United States, 59405-5309 |
| Frontier Cancer Center | Great Falls, Montana, United States, 59405 |
| Northern Montana Hospital | Havre, Montana, United States, 59501 |
| St. Peter's Hospital | Helena, Montana, United States, 59601 |
| Glacier Oncology, PLLC | Kalispell, Montana, United States, 59901 |
| Kalispell Medical Oncology at KRMC | Kalispell, Montana, United States, 59901 |
| Kalispell Regional Medical Center | Kalispell, Montana, United States, 59901 |
| Guardian Oncology and Center for Wellness | Missoula, Montana, United States, 59804 |
| Community Medical Center | Missoula, Montana, United States, 59801 |
| Montana Cancer Specialists at Montana Cancer Center | Missoula, Montana, United States, 59807-7877 |
| Montana Cancer Center at St. Patrick Hospital and Health Sciences Center | Missoula, Montana, United States, 59807 |
| Wayne Memorial Hospital, Incorporated | Goldsboro, North Carolina, United States, 27534 |
| Rutherford Hospital | Rutherfordton, North Carolina, United States, 28139 |
| Cleveland Clinic Taussig Cancer Center | Cleveland, Ohio, United States, 44195 |
| AnMed Cancer Center | Anderson, South Carolina, United States, 29621 |
| Hollings Cancer Center at Medical University of South Carolina | Charleston, South Carolina, United States, 29425 |
| McLeod Regional Medical Center | Florence, South Carolina, United States, 29501 |
| Gibbs Regional Cancer Center at Spartanburg Regional Medical Center | Spartanburg, South Carolina, United States, 29303 |
| CCOP - Upstate Carolina | Spartanburg, South Carolina, United States, 29303 |
| Huntsman Cancer Institute at University of Utah | Salt Lake City, Utah, United States, 84112 |
| St. Joseph Cancer Center | Bellingham, Washington, United States, 98225 |
| Olympic Hematology and Oncology | Bremerton, Washington, United States, 98310 |
| Columbia Basin Hematology | Kennewick, Washington, United States, 99336 |
| Fred Hutchinson Cancer Research Center | Seattle, Washington, United States, 98104 |
| Harborview Medical Center | Seattle, Washington, United States, 98104 |
| Minor and James Medical, PLLC | Seattle, Washington, United States, 98104 |
| Group Health Central Hospital | Seattle, Washington, United States, 98112 |
| Polyclinic First Hill | Seattle, Washington, United States, 98122 |
| Swedish Cancer Institute at Swedish Medical Center - First Hill Campus | Seattle, Washington, United States, 98122-4307 |
| University Cancer Center at University of Washington Medical Center | Seattle, Washington, United States, 98195-6043 |
| Cancer Care Northwest - Spokane South | Spokane, Washington, United States, 99202 |
| Rocky Mountain Oncology | Casper, Wyoming, United States, 82609 |
| Welch Cancer Center at Sheridan Memorial Hospital | Sheridan, Wyoming, United States, 82801 |