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Trial record 1 of 1 for:    NCT01256398
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Dasatinib Followed by Stem Cell Transplant in Treating Older Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01256398
First received: December 7, 2010
Last updated: November 21, 2014
Last verified: July 2014

December 7, 2010
November 21, 2014
December 2010
February 2018   (final data collection date for primary outcome measure)
DFS [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Estimated using the Kaplan-Meier estimator. Proportions will be estimated using point as well as interval estimators. All interval estimators will be constructed using the finite sample size sampling distribution at the unadjusted two-sided level of 0.05.
Disease-free survival (DFS) at 3 years [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01256398 on ClinicalTrials.gov Archive Site
  • Probability of being BCR-ABL negative in the bone marrow and peripheral blood at the completion of the CNS prophylaxis course (restricted to those patients achieving a complete response [CR]) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Proportions will be estimated based on the combined and individual cohorts.
  • Feasibility of maintenance therapy in this patient population (restricted to those patients achieving a CR) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Proportions will be estimated based on the combined and individual cohorts.
  • OS [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier estimator. Proportions will be estimated using point as well as interval estimators. All interval estimators will be constructed using the finite sample size sampling distribution at the unadjusted two-sided level of 0.05.
  • DFS [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier estimator. Proportions will be estimated using point as well as interval estimators. All interval estimators will be constructed using the finite sample size sampling distribution at the unadjusted two-sided level of 0.05.
  • Response [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  • Probability of being BCR-ABL negative in the bone marrow and peripheral blood at the completion of the CNS prophylaxis course (restricted to those patients achieving a complete response [CR]) [ Designated as safety issue: No ]
  • Feasibility of maintenance therapy in this patient population (restricted to those patients achieving a CR) [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • DFS [ Designated as safety issue: No ]
  • Response [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Dasatinib Followed by Stem Cell Transplant in Treating Older Patients With Newly Diagnosed Acute Lymphoblastic Leukemia
A Phase II Study of Dasatinib (Sprycel®) (NSC #732517) as Primary Therapy Followed by Transplantation for Adults ≥ 18 Years With Newly Diagnosed PH+ Acute Lymphoblastic Leukemia by CALGB, ECOG AND SWOG

This phase II clinical trial studies 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, may interfere with the ability of cancer cells to grow and spread. Giving more than one drug (combination chemotherapy) and giving dasatinib together with chemotherapy may kill more cancer cells.

PRIMARY OBJECTIVES:

I. Estimate the disease-free survival (DFS) and overall survival (OS) profiles in newly diagnosed patients 18 years or older who have Philadelphia chromosome positive (Ph+) (BCR/(v-abl Abelson murine leukemia viral oncogene homolog [ABL]+) acute lymphoblastic leukemia (ALL) receiving sequential dasatinib followed by allogeneic or autologous hematopoietic cell transplant (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 quantitative-polymerase chain reaction (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.

IV. Study the safety and efficacy of autologous HCT following therapy with dasatinib.

V. Study the safety and efficacy of reduced-intensity preparatory regimen followed by an allogeneic HCT following induction therapy with dasatinib.

VI. Study the safety and efficacy of dasatinib maintenance administered after allogeneic or autologous HCT or chemotherapy.

VII. Correlate plasma and cerebrospinal fluid (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.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1
  • Untreated Adult Acute Lymphoblastic Leukemia
  • Biological: Alemtuzumab
    Given IV
    Other Names:
    • Campath
    • LDP-03
    • MabCampath
    • MoAb CD52
  • Drug: Dasatinib
    Given PO
    Other Names:
    • BMS-354825
    • Sprycel
  • Drug: Daunorubicin Hydrochloride
    Given IV
    Other Names:
    • DNM
    • DNR
    • DRB
  • Drug: Fludarabine Phosphate
    Given IV
    Other Names:
    • 2-F-ara-AMP
    • Beneflur
    • SH T 586
  • Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
    Undergo peripheral blood allogeneic HCT
    Other Names:
    • HSC
    • HSCT
  • Procedure: Autologous Hematopoietic Stem Cell Transplantation
    Undergo peripheral blood autologous HCT
    Other Name: Autologous Stem Cell Transplantation
  • Procedure: In Vitro-Treated Peripheral Blood Stem Cell Transplantation
    Undergo peripheral blood autologous or allogeneic HCT
    Other Names:
    • in vitro-treated PBPC transplantation
    • in vitro-treated peripheral blood progenitor cell transplantation
  • Drug: Dexamethasone
    Given PO or IV
    Other Name: DM
  • Drug: Cyclophosphamide
    Given IV
  • Biological: Filgrastim
    Given SC
    Other Names:
    • G-CSF
    • Nivestim
    • r-metHuG-CSF
  • Biological: Pegfilgrastim
    Given SC
    Other Names:
    • Filgrastim SD-01
    • GCSF-SD01
    • Neulasta
  • Drug: Methotrexate
    Given IT, IV, or PO
  • Drug: Leucovorin Calcium
    Given IV or PO
    Other Name: CF
  • Drug: Melphalan
    Given IV
    Other Name: Alkeran
  • Drug: Tacrolimus
    Given IV or PO
    Other Names:
    • Advagraf
    • FK 506
  • Drug: Etoposide Phosphate
    Given IV
    Other Names:
    • ETOP
    • Etopophos
  • Drug: Cytarabine
    Given IV
    Other Names:
    • CHX-3311
    • U-19920
  • Drug: Mercaptopurine
    Given PO
  • Drug: Vincristine Sulfate
    Given IV
    Other Names:
    • Kyocristine
    • Oncovin
    • VCR
    • Vincasar
  • Other: Pharmacological Study
    Correlative studies
    Other Name: pharmacological studies
  • Other: Laboratory Biomarker Analysis
    Correlative studies
Experimental: Treatment (chemotherapy, transplant)
See Detailed Description
Interventions:
  • Biological: Alemtuzumab
  • Drug: Dasatinib
  • Drug: Daunorubicin Hydrochloride
  • Drug: Fludarabine Phosphate
  • Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
  • Procedure: Autologous Hematopoietic Stem Cell Transplantation
  • Procedure: In Vitro-Treated Peripheral Blood Stem Cell Transplantation
  • Drug: Dexamethasone
  • Drug: Cyclophosphamide
  • Biological: Filgrastim
  • Biological: Pegfilgrastim
  • Drug: Methotrexate
  • Drug: Leucovorin Calcium
  • Drug: Melphalan
  • Drug: Tacrolimus
  • Drug: Etoposide Phosphate
  • Drug: Cytarabine
  • Drug: Mercaptopurine
  • Drug: Vincristine Sulfate
  • Other: Pharmacological Study
  • Other: Laboratory Biomarker Analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
66
Not Provided
February 2018   (final data collection date for primary outcome measure)

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 fluorescent in situ hybridization [FISH]) in a Cruise Lines International Association (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
  • 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)
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01256398
NCI-2011-02621, NCI-2011-02621, CDR0000690286, CALGB-10701, CALGB 10701/CTSU C10701, CALGB 10701/CTSU C10701, CALGB-10701, U10CA031946
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Meir Wetzler Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP