Basic Trial Information
Trial Description
Summary
Further Trial Information
Eligibility Criteria
Trial Contact Information
| Phase | Type | Status | Age | Sponsor | Protocol IDs |
|---|---|---|---|---|---|
| Phase II | Biomarker/Laboratory analysis, Treatment | Active | 50 and over | NCI | NCI-2011-02621 CALGB 10701, CDR0000690286, CALGB 10701/CTSU C10701, U10CA031946, NCT01256398 |
Summary
This phase II clinical trial is studying how well dasatinib followed by stem cell transplant works in treating older patients with newly diagnosed acute lymphoblastic leukemia. Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving chemotherapy before a stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. Monoclonal antibodies, such as alemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving more than one drug (combination chemotherapy) and giving dasatinib together with chemotherapy may kill more cancer cells.
Further Study Information
PRIMARY OBJECTIVES:
I. Estimate the disease-free survival (DFS) and overall survival (OS) profiles in newly diagnosed patients 18 years or older who have Ph+ (BCR/ABL+) ALL receiving sequential dasatinib followed by allogeneic or autologous HCT or chemotherapy followed by dasatinib maintenance.
SECONDARY OBJECTIVES:
I. Compare the OS and DFS profiles for each of the three cohorts to those from similar populations from other studies.
II. Determine the ability of dasatinib to produce or maintain a BCR/ABL-negative status, as judged by Q-PCR following sequential dasatinib, chemotherapy, and HCT.
III. Determine the feasibility of collecting adequate peripheral blood stem cells for autologous HCT following dasatinib therapy and assess for residual Ph+ (BCR/ABL+) cells by Q-PCR.Study the safety and efficacy of autologous HCT following therapy with dasatinib.
IV. Study the safety and efficacy of reduced-intensity preparatory regimen followed by an allogeneic HCT following induction therapy with dasatinib.
V. Study the safety and efficacy of dasatinib maintenance administered after allogeneic or autologous HCT or chemotherapy.
VI. Correlate plasma and CSF levels of dasatinib when given orally during induction.
OUTLINE:
REMISSION INDUCTION THERAPY (RIT): Patients receive dasatinib orally (PO) daily continuously and dexamethasone PO or intravenously (IV) on days 1-7.
EARLY INTENSIFICATION THERAPY: Patients with bone marrow =< 20% blasts are assigned to cohort A and patients with bone marrow > 20% blasts are assigned to cohort B.
COHORT A: Patients receive dasatinib and dexamethasone as in RIT.
COHORT B: Patients receive dasatinib and dexamethasone as in RIT, and vincristine sulfate IV and daunorubicin hydrochloride IV on days 1, 8, and 15. Patients who do NOT achieve a complete response (CR) or CR with incomplete hematologic recovery based on bone marrow continue on to second induction therapy; patients who achieve a hematologic and morphologic CR continue on to CNS prophylaxis therapy.
SECOND INDUCTION THERAPY: Patients receive dasatinib and dexamethasone as in RIT, cyclophosphamide IV on day 1, daunorubicin hydrochloride IV and vincristine sulfate IV on days 1 and 8, and filgrastim subcutaneously (SC) beginning on day 9 and continuing for >= 7 days or one dose of pegfilgrastim on day 9.
CNS PROPHYLAXIS THERAPY: Patients receive dasatinib PO daily continuously during CNS prophylaxis therapy; methotrexate intrathecally (IT), vincristine sulfate IV, and methotrexate IV over 3 hours on days 1, 15, and 29; methotrexate PO every 6 hours for a total of 4 doses each on days 1-2, 15-16, and 29-30; leucovorin calcium IV on days 2, 16, and 30; and leucovorin PO calcium every 6 hours for a total of 8 doses each on days 3-4, 17-18, and 31-32.
TRANSPLANTATION OR ALTERNATIVE CHEMOTHERAPY AND MAINTENANCE THERAPY: Patients aged 50-70 years with an HLA-matched related or unrelated donor are assigned to allogeneic transplantation, patients aged 50-70 years without an HLA-matched related or unrelated donor are assigned to autologous transplantation, and patients aged > 70 years or who are not transplantation candidates are assigned to alternative chemotherapy.
ALLOGENEIC TRANSPLANTATION: Patients receive fludarabine phosphate IV over 30 minutes and alemtuzumab IV over 30 minutes on days -7 through -3 and melphalan IV over 30 minutes on day -2. Patients undergo allogeneic peripheral blood stem cell transplantation (PBSCT) on day 0. Patients then receive filgrastim SC beginning on day 1 and continuing until count recovery and tacrolimus IV or PO beginning on day -2 and beginning to taper on day 100 (for matched related donors) or day 180 (for mismatched related or unrelated donors). Beginning on day 30, patients receive dasatinib PO daily as maintenance therapy. Treatment continues for >= 12 months in the absence of disease progression.
AUTOLOGOUS TRANSPLANTATION:
MOBILIZATION: Patients receive etoposide phosphate IV continuously on days 1-4, high-dose cytarabine IV over 2 hours every 12 hours for a total of 8 doses on days 1-4, and filgrastim SC once or twice daily beginning on day 14 and continuing until peripheral blood stem cell collection is complete or WBC > 50,000/μL.
LEUKAPHERESIS: Patients undergo leukapheresis beginning when WBC > 10,000/μL for a target collection of >= 5 x 10^6 CD34+ cells/kg. After completion of stem cell collection, patients receive dasatinib PO twice daily until 3 days before transplantation.
TRANSPLANTATION: Beginning >= 4 weeks after recovery from toxicity related to previous treatment, patients receive melphalan IV over 30 minutes on days -2 and -1. Patients undergo autologous PBSCT on day 0. Patients then receive filgrastim SC beginning on day 0 and continuing until count recovery.
MAINTENANCE THERAPY: Beginning on day 30, patients receive dasatinib PO once daily. Treatment continues for >= 12 months in the absence of disease progression.
ALTERNATIVE CHEMOTHERAPY: Beginning 3-10 days after completion of CNS prophylaxis therapy, patients receive etoposide phosphate IV continuously on days 1-4, high-dose cytarabine IV over 2 hours every 12 hours for a total of 8 doses on days 1-4, and filgrastim SC once or twice daily beginning on day 14 and continuing until count recovery.
MAINTENANCE THERAPY: Patients receive dasatinib PO once daily beginning on day 30. Patients also receive vincristine sulfate IV every 4 weeks, dexamethasone for 5 days every 4 weeks, mercaptopurine PO once daily, and methotrexate PO once weekly. Treatment continues for >= 12 months in the absence of disease progression.
NOTE: Patients with CNS leukemia or testicular disease may receive additional treatment.
After completion of study treatment, patients are followed up every month for 1 year, every 3 months for 2 years, every 6 months for 2 years, and every year for 5 years.
Eligibility Criteria
Inclusion Criteria:
- Unequivocal histologic diagnosis of ALL
- Detection of the t(9;22)(q34;q11) or 3-way variant by metaphase cytogenetics or BCR-ABL positive status by molecular analysis (Q-PCR or FISH) in a CLIA-approved laboratory
- No prior therapy except up to one week of corticosteroids and/or hydroxyurea to enable time for the detection of t(9;22)(q34;q11) or BCR/ABL
- Enrolled on required companion study CALGB-8461 (Cytogenetic Studies in Acute Leukemia)
- 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 dasatinib to allow complete clearance of drug and its principal metabolites from the body; in women of childbearing potential, a pregnancy test will be required at study entry
- Left ventricular ejection fraction >= lower limit of institutional normal
- No myocardial infarction within 6 months
- No ventricular tachyarrhythmia within 6 months
- No major conduction abnormality (unless a cardiac pacemaker is present)
Trial Lead Organizations/Sponsors
National Cancer Institute
| Meir Wetzler |  | Principal Investigator |
Trial Sites
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| U.S.A. | |||
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| California | |||
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| Stanford | |||
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| Stanford Cancer Center | |||
| Michaela Liedtke | Ph: 650-498-7061 | ||
| Email: clinicaltrials@med.stanford.edu | |||
| Colorado | |||
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| Aurora | |||
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| Medical Center of Aurora - South Campus | |||
| Eduardo R. Pajon | Ph: 888-785-6789 | ||
| Boulder | |||
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| Boulder Community Hospital | |||
| Eduardo R. Pajon | Ph: 888-785-6789 | ||
| Colorado Springs | |||
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| Penrose Cancer Center at Penrose Hospital | |||
| Eduardo R. Pajon | Ph: 888-785-6789 | ||
| Denver | |||
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| Presbyterian - St. Luke's Medical Center | |||
| Eduardo R. Pajon | Ph: 888-785-6789 | ||
| St. Anthony Central Hospital | |||
| Eduardo R. Pajon | Ph: 888-785-6789 | ||
| St. Joseph Hospital | |||
| Eduardo R. Pajon | Ph: 888-785-6789 | ||
| Englewood | |||
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| Swedish Medical Center | |||
| Eduardo R. Pajon | Ph: 888-785-6789 | ||
| Greeley | |||
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| North Colorado Medical Center | |||
| Eduardo R. Pajon | Ph: 888-785-6789 | ||
| Littleton | |||
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| Littleton Adventist Hospital | |||
| Eduardo R. Pajon | Ph: 888-785-6789 | ||
| Lone Tree | |||
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| Sky Ridge Medical Center | |||
| Eduardo R. Pajon | Ph: 888-785-6789 | ||
| Longmont | |||
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| Hope Cancer Care Center at Longmont United Hospital | |||
| Eduardo R. Pajon | Ph: 888-785-6789 | ||
| Loveland | |||
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| McKee Medical Center | |||
| Eduardo R. Pajon | Ph: 888-785-6789 | ||
| Pueblo | |||
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| St. Mary - Corwin Regional Medical Center | |||
| Eduardo R. Pajon | Ph: 888-785-6789 | ||
| Wheat Ridge | |||
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| Exempla Lutheran Medical Center | |||
| Eduardo R. Pajon | Ph: 888-785-6789 | ||
| Delaware | |||
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| Lewes | |||
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| Tunnell Cancer Center at Beebe Medical Center | |||
| Frank Beardell | Ph: 302-733-6227 | ||
| Newark | |||
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| Helen F. Graham Cancer Center at Christiana Hospital | |||
| Frank Beardell | Ph: 302-733-6227 | ||
| Florida | |||
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| Orlando | |||
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| Florida Hospital Cancer Institute at Florida Hospital Orlando | |||
| Lee M. Zehngebot | Ph: 407-303-5623 | ||
| Illinois | |||
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| Chicago | |||
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| Robert H. Lurie Comprehensive Cancer Center at Northwestern University | |||
| Olga Frankfurt | Ph: 312-695-1301 | ||
| Email: cancer@northwestern.edu | |||
| University of Chicago Cancer Research Center | |||
| Wendy Stock | Ph: 773-834-7424 | ||
| Kankakee | |||
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| Provena St. Mary's Regional Cancer Center - Kankakee | |||
| Olga Frankfurt | Ph: 312-695-1301 | ||
| Email: cancer@northwestern.edu | |||
| Libertyville | |||
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| North Shore Oncology and Hematology Associates, Limited - Libertyville | |||
| Olga Frankfurt | Ph: 312-695-1301 | ||
| Email: cancer@northwestern.edu | |||
| Niles | |||
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| Cancer Care and Hematology Specialists of Chicagoland - Niles | |||
| Olga Frankfurt | Ph: 312-695-1301 | ||
| Email: cancer@northwestern.edu | |||
| Skokie | |||
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| Hematology Oncology Associates - Skokie | |||
| Olga Frankfurt | Ph: 312-695-1301 | ||
| Email: cancer@northwestern.edu | |||
| Indiana | |||
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| Fort Wayne | |||
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| Fort Wayne Medical Oncology and Hematology | |||
| Sreenivasa Rao Nattam | Ph: 260-484-8830 | ||
| Email: ledgar@fwmoh.com | |||
| Kansas | |||
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| Dodge City | |||
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| Cancer Center of Kansas, PA - Dodge City | |||
| Shaker R. Dakhil | Ph: 316-262-4467 | ||
| El Dorado | |||
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| Cancer Center of Kansas, PA - El Dorado | |||
| Shaker R. Dakhil | Ph: 316-262-4467 | ||
| Lawrence | |||
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| Lawrence Memorial Hospital | |||
| Shaker R. Dakhil | Ph: 316-262-4467 | ||
| Salina | |||
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| Cancer Center of Kansas, PA - Salina | |||
| Shaker R. Dakhil | Ph: 316-262-4467 | ||
| Wellington | |||
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| Cancer Center of Kansas, PA - Wellington | |||
| Shaker R. Dakhil | Ph: 316-262-4467 | ||
| Wichita | |||
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| Associates in Women's Health, PA - North Hillside | |||
| Shaker R. Dakhil | Ph: 316-262-4467 | ||
| Cancer Center of Kansas, PA - Medical Arts Tower | |||
| Shaker R. Dakhil | Ph: 316-262-4467 | ||
| Cancer Center of Kansas, PA - Wichita | |||
| Shaker R. Dakhil | Ph: 316-262-4467 | ||
| CCOP - Wichita | |||
| Shaker R. Dakhil | Ph: 316-262-4467 | ||
| Via Christi Cancer Center at Via Christi Regional Medical Center | |||
| Shaker R. Dakhil | Ph: 316-262-4467 | ||
| Wesley Medical Center | |||
| Shaker R. Dakhil | Ph: 316-262-4467 | ||
| Winfield | |||
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| Cancer Center of Kansas, PA - Winfield | |||
| Shaker R. Dakhil | Ph: 316-262-4467 | ||
| Maine | |||
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| Augusta | |||
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| Harold Alfond Center for Cancer Care | |||
| Thomas Henry Openshaw | Ph: 207-973-4274 | ||
| Bangor | |||
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| CancerCare of Maine at Eastern Maine Medical Center | |||
| Thomas Henry Openshaw | Ph: 207-973-4274 | ||
| Maryland | |||
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| Elkton MD | |||
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| Union Hospital of Cecil County | |||
| Frank Beardell | Ph: 302-733-6227 | ||
| Missouri | |||
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| Saint Louis | |||
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| Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis | |||
| Geoffrey L Uy | Ph: 800-600-3606 | ||
| Email: info@siteman.wustl.edu | |||
| Nebraska | |||
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| Omaha | |||
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| UNMC Eppley Cancer Center at the University of Nebraska Medical Center | |||
| Lori J. Maness | Ph: 800-999-5465 | ||
| New Hampshire | |||
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| Lebanon | |||
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| Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center | |||
| John M Hill | Ph: 800-639-6918 | ||
| Email: cancer.research.nurse@dartmouth.edu | |||
| New Jersey | |||
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| Camden | |||
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| Cancer Institute of New Jersey at Cooper University Hospital - Camden | |||
| Frank Beardell | Ph: 302-733-6227 | ||
| New York | |||
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| Buffalo | |||
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| Roswell Park Cancer Institute | |||
| Meir Wetzler | Ph: 877-275-7724 | ||
| Lake Success | |||
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| Monter Cancer Center of the North Shore-LIJ Health System | |||
| Ruthee-Lu Bayer | Ph: 516-562-3467 | ||
| Manhasset | |||
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| CCOP - North Shore University Hospital | |||
| Ruthee-Lu Bayer | Ph: 516-562-3467 | ||
| Don Monti Comprehensive Cancer Center at North Shore University Hospital | |||
| Ruthee-Lu Bayer | Ph: 516-562-3467 | ||
| New Hyde Park | |||
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| Long Island Jewish Medical Center | |||
| Ruthee-Lu Bayer | Ph: 516-562-3467 | ||
| New York | |||
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| New York Weill Cornell Cancer Center at Cornell University | |||
| Ellen K Ritchie | Ph: 212-746-1848 | ||
| Rochester | |||
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| James P. Wilmot Cancer Center at University of Rochester Medical Center | |||
| Jonathan W Friedberg | Ph: 585-275-5830 | ||
| North Carolina | |||
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| Winston-Salem | |||
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| Wake Forest University Comprehensive Cancer Center | |||
| Bayard L. Powell | Ph: 336-713-6771 | ||
| Ohio | |||
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| Cincinnati | |||
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| Jewish Hospital Cancer Center | |||
| James H. Essell | Ph: 513-585-2859 | ||
| Wisconsin | |||
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| La Crosse | |||
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| Gundersen Lutheran Center for Cancer and Blood | |||
| Kurt Oettel | Ph: 608-775-2385 | ||
| Email: cancerctr@gundluth.org | |||
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01256398
Information obtained from ClinicalTrials.gov on May 06, 2013
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