Clinical trial NCT01256398: Dasatinib Followed by Stem Cell Transplant in Treating Older Patients With Newly Diagnosed Acute Lymphoblastic Leukemia
Official title: A Phase II Study of Dasatinib (Sprycel&#174;) (NSC #732517) as Primary Therapy Followed by Transplantation for Adults &gt;/= 18 Years With Newly Diagnosed Ph+ Acute Lymphoblastic Leukemia by CALGB, ECOG and SWOG
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Lymphoblastic Leukemia
Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2010-12-08
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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: As of 8/21/2014, no new patients may be enrolled on E3903.

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 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)

Primary outcomes:
measure: Disease Free Survival Defined From the Date of First Induction Complete Response (CR) to Relapse or Death Due to Any Cause
timeFrame: At 3 years after CR
Secondary outcomes:
measure: 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 CR)
timeFrame: 10 years
measure: Feasibility of Maintenance Therapy in This Patient Population (Restricted to Those Patients Achieving a CR). Feasibility Will be Defined as the Number of Deaths Ocuring.
timeFrame: 10 years
measure: Overall Survival (OS)
timeFrame: 10 years
measure: Disease Free Survival (DFS)
timeFrame: 10 years
measure: Response
timeFrame: 10 years
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford Cancer Institute Palo Alto
state: California
city: Aurora
country: United States
facility: The Medical Center of Aurora
state: Colorado
city: Boulder
country: United States
facility: Boulder Community Hospital
state: Colorado
city: Boulder
country: United States
facility: Rocky Mountain Cancer Centers-Boulder
state: Colorado
city: Colorado Springs
country: United States
facility: Penrose-Saint Francis Healthcare
state: Colorado
city: Colorado Springs
country: United States
facility: Rocky Mountain Cancer Centers-Penrose
state: Colorado
city: Denver
country: United States
facility: Porter Adventist Hospital
state: Colorado
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Denver
country: United States
facility: Presbyterian - Saint Lukes Medical Center - Health One
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers-Midtown
state: Colorado
city: Denver
country: United States
facility: SCL Health Saint Joseph Hospital
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers-Rose
state: Colorado
city: Denver
country: United States
facility: Rose Medical Center
state: Colorado
city: Denver
country: United States
facility: Western States Cancer Research NCORP
state: Colorado
city: Durango
country: United States
facility: Mercy Medical Center
state: Colorado
city: Englewood
country: United States
facility: Mountain Blue Cancer Care Center - Swedish
state: Colorado
city: Englewood
country: United States
facility: Swedish Medical Center
state: Colorado
city: Golden
country: United States
facility: Mountain Blue Cancer Care Center
state: Colorado
city: Greeley
country: United States
facility: North Colorado Medical Center
state: Colorado
city: Greenwood Village
country: United States
facility: Rocky Mountain Cancer Centers-Greenwood Village
state: Colorado
city: Lakewood
country: United States
facility: Rocky Mountain Cancer Centers-Lakewood
state: Colorado
city: Lakewood
country: United States
facility: Saint Anthony Hospital
state: Colorado
city: Littleton
country: United States
facility: Littleton Adventist Hospital
state: Colorado
city: Lone Tree
country: United States
facility: Rocky Mountain Cancer Centers-Sky Ridge
state: Colorado
city: Lone Tree
country: United States
facility: Sky Ridge Medical Center
state: Colorado
city: Longmont
country: United States
facility: Longmont United Hospital
state: Colorado
city: Longmont
country: United States
facility: Rocky Mountain Cancer Centers-Longmont
state: Colorado
city: Loveland
country: United States
facility: McKee Medical Center
state: Colorado
city: Parker
country: United States
facility: Parker Adventist Hospital
state: Colorado
city: Parker
country: United States
facility: Rocky Mountain Cancer Centers-Parker
state: Colorado
city: Pueblo
country: United States
facility: Saint Mary Corwin Medical Center
state: Colorado
city: Pueblo
country: United States
facility: Rocky Mountain Cancer Centers - Pueblo
state: Colorado
city: Wheat Ridge
country: United States
facility: SCL Health Lutheran Medical Center
state: Colorado
city: Lewes
country: United States
facility: Beebe Medical Center
state: Delaware
city: Newark
country: United States
facility: Christiana Gynecologic Oncology LLC
state: Delaware
city: Newark
country: United States
facility: Delaware Clinical and Laboratory Physicians PA
state: Delaware
city: Newark
country: United States
facility: Helen F Graham Cancer Center
state: Delaware
city: Newark
country: United States
facility: Medical Oncology Hematology Consultants PA
state: Delaware
city: Newark
country: United States
facility: Christiana Care Health System-Christiana Hospital
state: Delaware
city: Rehoboth Beach
country: United States
facility: Beebe Health Campus
state: Delaware
city: Seaford
country: United States
facility: TidalHealth Nanticoke / Allen Cancer Center
state: Delaware
city: Wilmington
country: United States
facility: Christiana Care Health System-Wilmington Hospital
state: Delaware
city: Orlando
country: United States
facility: AdventHealth Orlando
state: Florida
city: Chicago
country: United States
facility: Hematology and Oncology Associates
state: Illinois
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Illinois
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Kankakee
country: United States
facility: Presence Saint Mary's Hospital
state: Illinois
city: Libertyville
country: United States
facility: AMG Libertyville - Oncology
state: Illinois
city: Niles
country: United States
facility: Illinois Cancer Specialists-Niles
state: Illinois
city: Rockford
country: United States
facility: SwedishAmerican Regional Cancer Center/ACT
state: Illinois
city: Skokie
country: United States
facility: Hematology Oncology Associates of Illinois - Skokie
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology Inc-Parkview
state: Indiana
city: Chanute
country: United States
facility: Cancer Center of Kansas - Chanute
state: Kansas
city: Dodge City
country: United States
facility: Cancer Center of Kansas - Dodge City
state: Kansas
city: El Dorado
country: United States
facility: Cancer Center of Kansas - El Dorado
state: Kansas
city: Fort Scott
country: United States
facility: Cancer Center of Kansas - Fort Scott
state: Kansas
city: Independence
country: United States
facility: Cancer Center of Kansas-Independence
state: Kansas
city: Kansas City
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Kingman
country: United States
facility: Cancer Center of Kansas-Kingman
state: Kansas
city: Lawrence
country: United States
facility: Lawrence Memorial Hospital
state: Kansas
city: Liberal
country: United States
facility: Cancer Center of Kansas-Liberal
state: Kansas
city: Manhattan
country: United States
facility: Cancer Center of Kansas-Manhattan
state: Kansas
city: McPherson
country: United States
facility: Cancer Center of Kansas - McPherson
state: Kansas
city: Newton
country: United States
facility: Cancer Center of Kansas - Newton
state: Kansas
city: Parsons
country: United States
facility: Cancer Center of Kansas - Parsons
state: Kansas
city: Pratt
country: United States
facility: Cancer Center of Kansas - Pratt
state: Kansas
city: Salina
country: United States
facility: Cancer Center of Kansas - Salina
state: Kansas
city: Wellington
country: United States
facility: Cancer Center of Kansas - Wellington
state: Kansas
city: Wichita
country: United States
facility: Associates In Womens Health
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas-Wichita Medical Arts Tower
state: Kansas
city: Wichita
country: United States
facility: Ascension Via Christi Hospitals Wichita
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas - Wichita
state: Kansas
city: Wichita
country: United States
facility: Wesley Medical Center
state: Kansas
city: Wichita
country: United States
facility: Wichita NCI Community Oncology Research Program
state: Kansas
city: Winfield
country: United States
facility: Cancer Center of Kansas - Winfield
state: Kansas
city: Augusta
country: United States
facility: Harold Alfond Center for Cancer Care
state: Maine
city: Bangor
country: United States
facility: Eastern Maine Medical Center
state: Maine
city: Elkton
country: United States
facility: Christiana Care - Union Hospital
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Camden
country: United States
facility: Cooper Hospital University Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Lake Success
country: United States
facility: Northwell Health NCORP
state: New York
city: Lake Success
country: United States
facility: Northwell Health/Center for Advanced Medicine
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New Hyde Park
country: United States
facility: Long Island Jewish Medical Center
state: New York
city: New York
country: United States
facility: NYP/Weill Cornell Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Cincinnati
country: United States
facility: The Jewish Hospital
state: Ohio
city: Hershey
country: United States
facility: Penn State Milton S Hershey Medical Center
state: Pennsylvania
city: Burlington
country: United States
facility: University of Vermont and State Agricultural College
state: Vermont
city: La Crosse
country: United States
facility: Gundersen Lutheran Medical Center
state: Wisconsin
city: Cheyenne
country: United States
facility: Cheyenne Regional Medical Center-West
state: Wyoming
Study officials:
affiliation: Alliance for Clinical Trials in Oncology
name: Matthew J Wieduwilt
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wieduwilt MJ, Yin J, Wetzler M, Uy GL, Powell BL, Kolitz JE, Liedtke M, Stock W, Beumer JH, Mattison RJ, Storrick E, Christner SM, Lewis LD, Devine S, Stone RM, Larson RA. Dasatinib and dexamethasone followed by hematopoietic cell transplantation for adults with Ph-positive ALL. Blood Adv. 2021 Nov 23;5(22):4691-4700. doi: 10.1182/bloodadvances.2021004813.