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A Phase II Study of Dasatinib (Sprycel®) (IND #73969, NSC #732517) as Primary Therapy Followed by Transplantation for Adults >/= 18 Years With Newly Diagnosed Ph+ Acute Lymphoblastic Leukemia by CALGB, ECOG and SWOG


Phase 2
50 Years
N/A
Open (Enrolling)
Both
Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia, Untreated Adult Acute Lymphoblastic Leukemia

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Trial Information

A Phase II Study of Dasatinib (Sprycel®) (IND #73969, NSC #732517) as Primary Therapy Followed by Transplantation for Adults >/= 18 Years With Newly Diagnosed Ph+ Acute Lymphoblastic Leukemia by CALGB, ECOG and SWOG


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.


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)

Type of Study:

Interventional

Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Disease-free survival (DFS)

Outcome Description:

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.

Outcome Time Frame:

3 years

Safety Issue:

No

Principal Investigator

Meir Wetzler

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cancer and Leukemia Group B

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2011-02621

NCT ID:

NCT01256398

Start Date:

December 2010

Completion Date:

Related Keywords:

  • Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia
  • Untreated Adult Acute Lymphoblastic Leukemia
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Philadelphia Chromosome

Name

Location

Roswell Park Cancer InstituteBuffalo, New York  14263
Washington University School of MedicineSaint Louis, Missouri  63110
Boulder Community HospitalBoulder, Colorado  80301-9019
Swedish Medical CenterEnglewood, Colorado  80110
Sky Ridge Medical CenterLone Tree, Colorado  80124
North Shore University HospitalManhasset, New York  11030
Eastern Maine Medical CenterBangor, Maine  04401
University of Nebraska Medical CenterOmaha, Nebraska  68198-3330
Via Christi Regional Medical CenterWichita, Kansas  67214
Wesley Medical CenterWichita, Kansas  67214
Weill Medical College of Cornell UniversityNew York, New York  10021
Long Island Jewish Medical CenterNew Hyde Park, New York  11040
North Colorado Medical CenterGreeley, Colorado  80631
McKee Medical CenterLoveland, Colorado  80539
Cancer Center of Kansas - Dodge CityDodge City, Kansas  67801
Cancer Center of Kansas - SalinaSalina, Kansas  67042
Cancer Center of Kansas - WellingtonWellington, Kansas  67152
Associates in Womens HealthWichita, Kansas  67203
Cancer Center of Kansas - WinfieldWinfield, Kansas  67156
Beebe Medical CenterLewes, Delaware  19958
Hematology and Oncology AssociatesChicago, Illinois  60611
Exempla Lutheran Medical CenterWheat Ridge, Colorado  80033
Lawrence Memorial HospitalLawrence, Kansas  66044
Longmont United HospitalLongmont, Colorado  80501
Harold Alfond Center for Cancer CareAugusta, Maine  04330
Union Hospital of Cecil CountyElkton MD, Maryland  21921
Northwestern UniversityChicago, Illinois  60611
University of RochesterRochester, New York  14642
Dartmouth Hitchcock Medical CenterLebanon, New Hampshire  03756
Presbyterian - Saint Lukes Medical Center - Health OneDenver, Colorado  80218
Wichita CCOPWichita, Kansas  67214-3882
Florida HospitalOrlando, Florida  32803
University of Chicago Comprehensive Cancer CenterChicago, Illinois  60637-1470
Littleton Adventist HospitalLittleton, Colorado  80122
Wake Forest University Health SciencesWinston-Salem, North Carolina  27157
The Medical Center of AuroraAurora, Colorado  80012
Penrose-Saint Francis HealthcareColorado Springs, Colorado  80907
Saint Anthony Central HospitalDenver, Colorado  80204
Exempla Saint Joseph HospitalDenver, Colorado  80218
Saint Mary Corwin Medical CenterPueblo, Colorado  81004
Provena Saint Mary's HospitalKankakee, Illinois  60901
North Shore Hematology OncologyLibertyville, Illinois  60048
Hematology Oncology Associates of Illinois - SkokieSkokie, Illinois  60076
Fort Wayne Medical Oncology and Hematology Inc - State BoulevardFort Wayne, Indiana  46845
Cancer Center of Kansas - El DoradoEl Dorado, Kansas  67042
Cancer Center of Kansas-Wichita Medical Arts TowerWichita, Kansas  67208
Cancer Center of Kansas - Main OfficeWichita, Kansas  67214
Cooper Hospital University Medical CenterCamden, New Jersey  08103
Monter Cancer CenterLake Success, New York  11042
Gundersen LutheranLa Crosse, Wisconsin  54601
The Jewish HospitalCincinnati, Ohio  45236
Stanford University Hospitals and ClinicsStanford, California  94305
North Shore-LIJ Health System CCOPManhasset, New York  11030
Christiana Care Health System-Christiana HospitalNewark, Delaware  19718
Illinois Cancer Specialists-NilesNiles, Illinois  60714