Chemotherapy, Imatinib Mesylate, and Peripheral Stem Cell Transplantation in Treating Patients With Newly Diagnosed Acute Lymphoblastic Leukemia
- Conditions
- Adult Acute Lymphoblastic Leukemia in Remission
- Interventions
- Procedure: peripheral blood stem cell transplantationProcedure: autologous hematopoietic stem cell transplantationProcedure: allogeneic hematopoietic stem cell transplantationRadiation: total-body irradiationBiological: filgrastimOther: laboratory biomarker analysis
- Registration Number
- NCT00039377
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
This phase II trial studies how well giving imatinib mesylate together with chemotherapy and peripheral stem cell transplantation works in treating patients with newly diagnosed acute lymphoblastic leukemia. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Giving imatinib mesylate together with chemotherapy and peripheral stem cell transplantation may be an effective treatment for acute lymphoblastic leukemia.
- Detailed Description
PRIMARY OBJECTIVES:
I. Determine the activity of imatinib mesylate (Gleevec) to prolong disease-free survival (DFS) and overall survival in acute lymphoblastic leukemia (ALL) patients with t(9;22).
II. Determine the ability of imatinib mesylate (Gleevec) to produce or maintain a BCR-ABL-negative status, as judged by real-time-polymerase chain reaction (RT-PCR) following sequential chemotherapy, imatinib mesylate (Gleevec) and transplantation.
III. Determine the feasibility of collecting adequate peripheral blood stem cells for autologous transplantation following imatinib mesylate (Gleevec) therapy.
IV. Study the safety and efficacy of autologous peripheral stem cell transplantation following therapy with imatinib mesylate (Gleevec).
V. Study the safety and efficacy of allogeneic stem cell transplantation following therapy with imatinib mesylate (Gleevec).
VI. Study the safety and efficacy of imatinib mesylate (Gleevec) administered after allogeneic or autologous stem cell transplant.
OUTLINE:
COURSE I (remission induction): Patients receive 1 course of front-line induction therapy on a Cancer and Leukemia Group B (CALGB)/Southwest Oncology Group (SWOG) protocol prior to enrollment.
COURSE II (imatinib mesylate): Patients receive imatinib mesylate orally (PO) twice daily on days 1-28.
COURSE III (CNS prophylaxis): Within 7 days after completing course II, patients receive methotrexate intrathecally (IT), methotrexate intravenously (IV) over 3 hours, and vincristine sulfate IV on days 1, 8, and 15; methotrexate PO every 6 hours on days 1-2, 8-9, and 15-16; leucovorin calcium IV on days 2, 9, and 16; and leucovorin calcium PO every 6 hours on days 3, 4, 10, 11, 17, and 18.
COURSE IV (imatinib mesylate): After blood counts recover after completion of course III, patients receive imatinib mesylate as in course II.
COURSE V: Patients undergo allogeneic peripheral blood stem cell transplantation (PBSCT), autologous PBSCT, or no PBSCT.
COURSE Va (allogeneic PBSCT for patients with human leukocyte antigen \[HLA\]-matched sibling donor): Beginning 3-10 days after completion of course IV, patients with an HLA-matched sibling donor undergo total body irradiation (TBI) 2-3 times daily on days -7 to -4. Patients receive etoposide IV over 4 hours on day -3. Patients then undergo PBSCT on day 0. Patients then receive graft-vs-host disease prophylaxis with tacrolimus IV continuously on days -1 to 56 (or IV continuously on days -1 to 14 and then PO or IV every 12 hours on days 15-56) followed by a taper. Patients also receive methotrexate IV on days 1, 3, and 6, and filgrastim subcutaneously (SC) beginning on day 4 and continuing until blood counts recover.
COURSE Vb (autologous PBSCT for patients without HLA-matched sibling donor): Beginning 3-10 days after completion of course IV, patients without an HLA-matched sibling donor receive etoposide IV continuously and cytarabine IV over 2 hours on days 1-4. Patients also receive filgrastim SC beginning on day 14 and continuing until PBSC collection is complete. Patients receive imatinib mesylate PO twice daily beginning after completion of PBSC collection and continuing until 3 days before PBSCT. Patients then undergo TBI 2-3 times daily on days -8 to -5. Patients receive etoposide IV over 4 hours on day -4 and cyclophosphamide IV over 2 hours on day -2. Patients undergo PBSCT on day 0. Patients receive filgrastim SC beginning on day 0 and continuing until blood counts recover.
COURSE Vc (no transplantation for patients who are not transplant candidates): Beginning 3-10 days after completion of course IV, patients who are not candidates for PBSCT receive etoposide IV over 4 hours and cytarabine IV over 2 hours on days 1-4. Patients also receive filgrastim SC once or twice a day beginning on day 14 and continuing until blood counts recover.
COURSE VI: Patients receive imatinib mesylate PO once or twice daily beginning on day 30 post transplantation or on day 30 if no transplantation received and continuing for at least 1 year or until patient has 2 consecutive negative reverse transcriptase-polymerase chain reaction assays at least 3 months apart or until relapse.
After completion of study treatment, patients are followed up monthly for 1 year, every 3 months for 2 years, every 6 months for 2 years, then yearly for 5 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 58
-
Unequivocal histologic diagnosis of ALL
-
Detection of the t(9;22)(q34;q11) or 3-way variant by metaphase cytogenetics or BCR-ABL positive by molecular analysis (RT-PCR or fluorescence in situ hybridization [FISH})
-
Prior Therapy:
-
Complete or partial remission following one course of induction chemotherapy with an intensive 4 or 5 drug regimen (with or without imatinib mesylate) on a CALGB or SWOG ALL protocol for previously untreated ALL patients
- Note: The double induction regimen of SWOG S0333 is considered to be one course of induction chemotherapy for the purpose of this eligibility criterion; therefore, patients from S0333 may be eligible for this study only after completing the entire double induction regimen
-
Complete or partial remission following one course of therapy on any standard induction regimen (with or without imatinib mesylate) without prior enrollment on a cooperative group frontline protocol; in these instances, documentation of Philadelphia chromosome (Ph)+ positivity may occur outside a CALGB or SWOG laboratory
- Note: CALGB institutions must enroll patients on CALGB 9862 and submission of an initial sample for the companion trial must occur at time of enrollment on CALGB C10001; enrollment on companion studies CALGB 8461 and 9665 is not required
-
-
No more than six weeks of prior imatinib mesylate during induction therapy before study enrollment
-
Non-pregnant and non-nursing; treatment under this protocol would expose an unborn child to significant risks; women and men of reproductive potential should agree to use an effective means of birth control and contraception should continue for three months after the last dose of imatinib mesylate (Gleevec) to allow complete clearance of drug and its principle metabolites from the body; in women of childbearing potential, a pregnancy test will be required at study entry
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment (imatinib mesylate, chemotherapy, PBSCT) imatinib mesylate See Detailed Description. Treatment (imatinib mesylate, chemotherapy, PBSCT) etoposide See Detailed Description. Treatment (imatinib mesylate, chemotherapy, PBSCT) leucovorin calcium See Detailed Description. Treatment (imatinib mesylate, chemotherapy, PBSCT) peripheral blood stem cell transplantation See Detailed Description. Treatment (imatinib mesylate, chemotherapy, PBSCT) tacrolimus See Detailed Description. Treatment (imatinib mesylate, chemotherapy, PBSCT) filgrastim See Detailed Description. Treatment (imatinib mesylate, chemotherapy, PBSCT) vincristine sulfate See Detailed Description. Treatment (imatinib mesylate, chemotherapy, PBSCT) autologous hematopoietic stem cell transplantation See Detailed Description. Treatment (imatinib mesylate, chemotherapy, PBSCT) allogeneic hematopoietic stem cell transplantation See Detailed Description. Treatment (imatinib mesylate, chemotherapy, PBSCT) laboratory biomarker analysis See Detailed Description. Treatment (imatinib mesylate, chemotherapy, PBSCT) total-body irradiation See Detailed Description. Treatment (imatinib mesylate, chemotherapy, PBSCT) cyclophosphamide See Detailed Description. Treatment (imatinib mesylate, chemotherapy, PBSCT) methotrexate See Detailed Description. Treatment (imatinib mesylate, chemotherapy, PBSCT) cytarabine See Detailed Description.
- Primary Outcome Measures
Name Time Method Disease Free Survival Duration of treatment (up to 10 years) Disease-free survival (DFS) was measured as the interval from achievement of complete remission (CR) until relapse or death, regardless of cause; patients alive and in CR were censored at last follow-up. DFS was estimated using the Kaplan Meier method.
A complete remission (CR) was defined as recovery of morphologically normal bone marrow and blood counts (i.e., neutrophils \>= 1.5 x 10\^9/L and platelets \> 100 x 10\^9/L) and no circulating leukemic blasts or evidence of extramedullary leukemia and persisting for at least one month.
- Secondary Outcome Measures
Name Time Method 5 Year Disease-free Survival for Autologous & Allogeneic Transplant Groups 5 years from CR Percentage of patients who achieved a complete remission (CR) and were alive and relapse free at 5 years. The 5-year progression free survival was estimated using the Kaplan Meier method.
Number of Participants Who Achieved a BCR-ABL Response at 12 Months 12 months BCR-ABL response is defined in two ways: complete molecular response (CMR) and major molecular response (MMR).
Complete Molecular Response is defined as a Bcr-Abl (a fusion of gene of Bcr and ABl genes) ratio ≤0.0032% on the International Scale Bcr = breakpoint cluster gene Abl = abelson proto-oncogene
MMR is defined as Bcr-Abl (A fusion gene of the breakpoint cluster region \[Bcr\] gene and Abelson proto-oncogene \[Abl\] genes) transcript ratio ≤0.1% (≥ 3 log reduction of BCR-ABL transcripts from a standardized baseline), as detected by reverse transcriptase polymerase chain reaction \[RT-PCR\] (performed centrally).5 Year Overall Survival for Autologous & Allogeneic Transplant Groups 5 years from registration Percentage of patients who were alive at 5 years. The 5-year progression free survival was estimated using the Kaplan Meier method.
Overall Survival Duration of study (up to 10 years) Overall survival (OS) as the interval from the on-study date until death. OS was estimated using the Kaplan Meier method.
Trial Locations
- Locations (97)
Great Falls Clinic
🇺🇸Great Falls, Montana, United States
Mason District Hospital
🇺🇸Havana, Illinois, United States
Berdeaux, Donald MD (UIA Investigator)
🇺🇸Great Falls, Montana, United States
Guardian Oncology and Center for Wellness
🇺🇸Missoula, Montana, United States
Community Medical Hospital
🇺🇸Missoula, Montana, United States
Saint James Community Hospital and Cancer Treatment Center
🇺🇸Butte, Montana, United States
Montana Cancer Consortium CCOP
🇺🇸Billings, Montana, United States
Internal Medicine of Bozeman
🇺🇸Bozeman, Montana, United States
Northern Rockies Radiation Oncology Center
🇺🇸Billings, Montana, United States
Deaconess Medical Center
🇺🇸Billings, Montana, United States
Glacier Oncology PLLC
🇺🇸Kalispell, Montana, United States
Hematology-Oncology Centers of the Northern Rockies PC
🇺🇸Billings, Montana, United States
Bozeman Deaconess Cancer Center
🇺🇸Bozeman, Montana, United States
Saint Peter's Community Hospital
🇺🇸Helena, Montana, United States
Kalispell Medical Oncology
🇺🇸Kalispell, Montana, United States
Kalispell Regional Medical Center
🇺🇸Kalispell, Montana, United States
Saint Patrick Hospital - Community Hospital
🇺🇸Missoula, Montana, United States
North Shore University Hospital
🇺🇸Manhasset, New York, United States
Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
Weiss Memorial Hospital
🇺🇸Chicago, Illinois, United States
Blood and Marrow Transplant Group of Georgia
🇺🇸Atlanta, Georgia, United States
Illinois CancerCare Galesburg
🇺🇸Galesburg, Illinois, United States
Illinois CancerCare-Peoria
🇺🇸Peoria, Illinois, United States
OSF Saint Francis Medical Center
🇺🇸Peoria, Illinois, United States
Cancer Center of Kansas - Salina
🇺🇸Salina, Kansas, United States
Saint Joseph Medical Center
🇺🇸Bloomington, Illinois, United States
Eureka Hospital
🇺🇸Eureka, Illinois, United States
Galesburg Cottage Hospital
🇺🇸Galesburg, Illinois, United States
Illinois Oncology Research Association CCOP
🇺🇸Peoria, Illinois, United States
Pekin Cancer Treatment Center
🇺🇸Pekin, Illinois, United States
Saint Margaret's Hospital
🇺🇸Spring Valley, Illinois, United States
Cancer Center of Kansas-Kingman
🇺🇸Kingman, Kansas, United States
Pekin Hospital
🇺🇸Pekin, Illinois, United States
Radiation Oncology Practice Corporation Southwest
🇺🇸Overland Park, Kansas, United States
North Shore-LIJ Health System CCOP
🇺🇸Manhasset, New York, United States
Western Pennsylvania Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Cancer Center of Kansas-Wichita Medical Arts Tower
🇺🇸Wichita, Kansas, United States
Saint Luke's Cancer Institute
🇺🇸Kansas City, Missouri, United States
Radiation Oncology Practice Corporation - North
🇺🇸Kansas City, Missouri, United States
Cancer Center of Kansas - Chanute
🇺🇸Chanute, Kansas, United States
Radiation Oncology Center of Olathe
🇺🇸Olathe, Kansas, United States
Cancer Center of Kansas - Winfield
🇺🇸Winfield, Kansas, United States
Perry Memorial Hospital
🇺🇸Princeton, Illinois, United States
Long Island Jewish Medical Center
🇺🇸New Hyde Park, New York, United States
Eastern Maine Medical Center
🇺🇸Bangor, Maine, United States
Billings Clinic
🇺🇸Billings, Montana, United States
Radiation Oncology Practice Corporation South
🇺🇸Kansas City, Missouri, United States
Methodist Medical Center of Illinois
🇺🇸Peoria, Illinois, United States
Proctor Hospital
🇺🇸Peoria, Illinois, United States
Cancer Center of Kansas - El Dorado
🇺🇸El Dorado, Kansas, United States
Providence Medical Center
🇺🇸Kansas City, Kansas, United States
Lawrence Memorial Hospital
🇺🇸Lawrence, Kansas, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Fort Wayne Medical Oncology and Hematology Inc-Parkview
🇺🇸Fort Wayne, Indiana, United States
Commonwealth Hematology Oncology PC-Worcester
🇺🇸Worcester, Massachusetts, United States
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
🇺🇸Columbus, Ohio, United States
Illinois Valley Hospital
🇺🇸Peru, Illinois, United States
Cancer Center of Kansas - Dodge City
🇺🇸Dodge City, Kansas, United States
Salina Regional Health Center
🇺🇸Salina, Kansas, United States
Beverly Hospital
🇺🇸Beverly, Massachusetts, United States
Frisbie Hospital
🇺🇸Rochester, New Hampshire, United States
Weill Medical College of Cornell University
🇺🇸New York, New York, United States
State University of New York Upstate Medical University
🇺🇸Syracuse, New York, United States
Via Christi Regional Medical Center
🇺🇸Wichita, Kansas, United States
Cheshire Medical Center-Dartmouth-Hitchcock Keene
🇺🇸Keene, New Hampshire, United States
North Shore-LIJ Health System/Center for Advanced Medicine
🇺🇸New Hyde Park, New York, United States
Cancer Center of Kansas - Wellington
🇺🇸Wellington, Kansas, United States
Liberty Hospital
🇺🇸Liberty, Missouri, United States
Montana Cancer Specialists
🇺🇸Missoula, Montana, United States
University of Rochester
🇺🇸Rochester, New York, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Northeastern
🇺🇸St. Johnsbury, Vermont, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Graham Hospital Association
🇺🇸Canton, Illinois, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
Memorial Hospital
🇺🇸Carthage, Illinois, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Bromenn Regional Medical Center
🇺🇸Normal, Illinois, United States
Ottawa Regional Hospital and Healthcare Center
🇺🇸Ottawa, Illinois, United States
Mcdonough District Hospital
🇺🇸Macomb, Illinois, United States
Community Cancer Center Foundation
🇺🇸Normal, Illinois, United States
Hopedale Medical Complex - Hospital
🇺🇸Hopedale, Illinois, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Illinois CancerCare-Ottawa Clinic
🇺🇸Ottawa, Illinois, United States
Centerpoint Medical Center LLC
🇺🇸Independence, Missouri, United States
Saint Vincent Healthcare
🇺🇸Billings, Montana, United States
Bozeman Deaconess Hospital
🇺🇸Bozeman, Montana, United States
Kinston Medical Specialists PA
🇺🇸Kinston, North Carolina, United States
Oswego Hospital
🇺🇸Oswego, New York, United States
Welch Cancer Center
🇺🇸Sheridan, Wyoming, United States
Associates In Womens Health
🇺🇸Wichita, Kansas, United States
Cancer Center of Kansas - Main Office
🇺🇸Wichita, Kansas, United States
Wichita CCOP
🇺🇸Wichita, Kansas, United States
Cancer Center of Kansas - Newton
🇺🇸Newton, Kansas, United States
Cancer Center of Kansas - Parsons
🇺🇸Parsons, Kansas, United States
Cancer Center of Kansas - Pratt
🇺🇸Pratt, Kansas, United States
Addison Gilbert Hospital
🇺🇸Gloucester, Massachusetts, United States