Dasatinib Followed by Stem Cell Transplant in Treating Older Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01256398
• Other study ID #: NCI-2011-02621
• Secondary ID: NCI-2011-02621CA
• Status: Completed
• Phase: Phase 2
• Start date: December 14, 2010
• Est. completion date: November 15, 2021

Study information

• Verified date: March 2023
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: November 15, 2021
• Est. primary completion date: November 14, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Biological:
• Alemtuzumab
Given IV

Procedure:
• Allogeneic Hematopoietic Stem Cell Transplantation
Undergo peripheral blood allogeneic HCT
• Autologous Hematopoietic Stem Cell Transplantation
Undergo peripheral blood autologous HCT

Drug:
• Cyclophosphamide
Given IV
• Cytarabine
Given IV
• Dasatinib
Given PO
• Daunorubicin Hydrochloride
Given IV
• Dexamethasone
Given PO or IV
• Etoposide Phosphate
Given IV

Biological:
• Filgrastim
Given SC

Drug:
• Fludarabine Phosphate
Given IV

Procedure:
• In Vitro-Treated Peripheral Blood Stem Cell Transplantation
Undergo peripheral blood autologous or allogeneic HCT

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Leucovorin Calcium
Given IV or PO
• Melphalan
Given IV
• Mercaptopurine
Given PO
• Methotrexate
Given IT, IV, or PO

Biological:
• Pegfilgrastim
Given SC

Other:
• Pharmacological Study
Correlative studies

Drug:
• Tacrolimus
Given IV or PO
• Vincristine Sulfate
Given IV

Locations

Country	Name	City	State
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Harold Alfond Center for Cancer Care	Augusta	Maine
United States	The Medical Center of Aurora	Aurora	Colorado
United States	Eastern Maine Medical Center	Bangor	Maine
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Boulder Community Hospital	Boulder	Colorado
United States	Rocky Mountain Cancer Centers-Boulder	Boulder	Colorado
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	University of Vermont and State Agricultural College	Burlington	Vermont
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Cancer Center of Kansas - Chanute	Chanute	Kansas
United States	Cheyenne Regional Medical Center-West	Cheyenne	Wyoming
United States	Hematology and Oncology Associates	Chicago	Illinois
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	The Jewish Hospital	Cincinnati	Ohio
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado
United States	Rocky Mountain Cancer Centers-Midtown	Denver	Colorado
United States	Rocky Mountain Cancer Centers-Rose	Denver	Colorado
United States	Rose Medical Center	Denver	Colorado
United States	SCL Health Saint Joseph Hospital	Denver	Colorado
United States	Western States Cancer Research NCORP	Denver	Colorado
United States	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
United States	Mercy Medical Center	Durango	Colorado
United States	Cancer Center of Kansas - El Dorado	El Dorado	Kansas
United States	Christiana Care - Union Hospital	Elkton	Maryland
United States	Mountain Blue Cancer Care Center - Swedish	Englewood	Colorado
United States	Swedish Medical Center	Englewood	Colorado
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Fort Wayne Medical Oncology and Hematology Inc-Parkview	Fort Wayne	Indiana
United States	Mountain Blue Cancer Care Center	Golden	Colorado
United States	North Colorado Medical Center	Greeley	Colorado
United States	Rocky Mountain Cancer Centers-Greenwood Village	Greenwood Village	Colorado
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Presence Saint Mary's Hospital	Kankakee	Illinois
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	Cancer Center of Kansas-Kingman	Kingman	Kansas
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	Northwell Health NCORP	Lake Success	New York
United States	Northwell Health/Center for Advanced Medicine	Lake Success	New York
United States	Rocky Mountain Cancer Centers-Lakewood	Lakewood	Colorado
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Beebe Medical Center	Lewes	Delaware
United States	Cancer Center of Kansas-Liberal	Liberal	Kansas
United States	AMG Libertyville - Oncology	Libertyville	Illinois
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Rocky Mountain Cancer Centers-Sky Ridge	Lone Tree	Colorado
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Longmont United Hospital	Longmont	Colorado
United States	Rocky Mountain Cancer Centers-Longmont	Longmont	Colorado
United States	McKee Medical Center	Loveland	Colorado
United States	North Shore University Hospital	Manhasset	New York
United States	Cancer Center of Kansas-Manhattan	Manhattan	Kansas
United States	Cancer Center of Kansas - McPherson	McPherson	Kansas
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	NYP/Weill Cornell Medical Center	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Christiana Gynecologic Oncology LLC	Newark	Delaware
United States	Delaware Clinical and Laboratory Physicians PA	Newark	Delaware
United States	Helen F Graham Cancer Center	Newark	Delaware
United States	Medical Oncology Hematology Consultants PA	Newark	Delaware
United States	Cancer Center of Kansas - Newton	Newton	Kansas
United States	Illinois Cancer Specialists-Niles	Niles	Illinois
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	AdventHealth Orlando	Orlando	Florida
United States	Stanford Cancer Institute Palo Alto	Palo Alto	California
United States	Parker Adventist Hospital	Parker	Colorado
United States	Rocky Mountain Cancer Centers-Parker	Parker	Colorado
United States	Cancer Center of Kansas - Parsons	Parsons	Kansas
United States	Cancer Center of Kansas - Pratt	Pratt	Kansas
United States	Rocky Mountain Cancer Centers - Pueblo	Pueblo	Colorado
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	Beebe Health Campus	Rehoboth Beach	Delaware
United States	University of Rochester	Rochester	New York
United States	SwedishAmerican Regional Cancer Center/ACT	Rockford	Illinois
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Cancer Center of Kansas - Salina	Salina	Kansas
United States	TidalHealth Nanticoke / Allen Cancer Center	Seaford	Delaware
United States	Hematology Oncology Associates of Illinois - Skokie	Skokie	Illinois
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado
United States	Ascension Via Christi Hospitals Wichita	Wichita	Kansas
United States	Associates In Womens Health	Wichita	Kansas
United States	Cancer Center of Kansas - Wichita	Wichita	Kansas
United States	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas
United States	Wesley Medical Center	Wichita	Kansas
United States	Wichita NCI Community Oncology Research Program	Wichita	Kansas
United States	Christiana Care Health System-Wilmington Hospital	Wilmington	Delaware
United States	Cancer Center of Kansas - Winfield	Winfield	Kansas
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease Free Survival Defined From the Date of First Induction Complete Response (CR) to Relapse or Death Due to Any Cause	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.	At 3 years after CR
Secondary	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)	Proportions will be estimated based on the combined and individual cohorts.	10 years
Secondary	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.	Proportions will be estimated based on the combined and individual cohorts.	10 years
Secondary	Overall Survival (OS)	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.	10 years
Secondary	Disease Free Survival (DFS)	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.	10 years
Secondary	Response	Proportion of patients reaching a CR. A CR requires the following: an absolute neutrophil count (segs and bands) >1000/µL, no circulating blasts, platelets >100,000/µL; adequate bone marrow cellularity with trilineage hematopoiesis, and <5% marrow leukemia blast cells. All previous extramedullary manifestations of disease must be absent (e.g., lymphadenopathy, splenomegaly, skin or gum infiltration, testicular masses, or CNS involvement).	10 years