Sorafenib Tosylate and Chemotherapy in Treating Older Patients With Acute Myeloid Leukemia
|ClinicalTrials.gov Identifier: NCT01253070|
Recruitment Status : Active, not recruiting
First Posted : December 3, 2010
Results First Posted : February 11, 2016
Last Update Posted : November 16, 2016
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia (Megakaryoblastic) With t(1;22)(p13;q13); RBM15-MKL1 Acute Myeloid Leukemia With a Variant RARA Translocation Acute Myeloid Leukemia With Inv(3)(q21q26.2) or t(3;3)(q21;q26.2); RPN1-EVI1 Acute Myeloid Leukemia With t(6;9)(p23;q34); DEK-NUP214 Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL Acute Myeloid Leukemia With Variant MLL Translocations Untreated Adult Acute Myeloid Leukemia||Drug: Daunorubicin Hydrochloride Drug: Sorafenib Tosylate Drug: Cytarabine Procedure: Bone Marrow Aspiration Procedure: Biopsy Other: Laboratory Biomarker Analysis Other: Quality-of-Life Assessment Other: Questionnaire Administration||Phase 2|
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I. To determine if the 1-year overall survival rate of patients age >= 60 with fms-related tyrosine kinase 3 (FLT3)-internal-tandem duplications (ITD) AML treated with a sorafenib (sorafenib tosylate) containing induction and post-remission therapy is significantly higher than the historical 1-year overall survival rate of similar patients who were not treated with sorafenib.
I. To determine the rates of complete remission (CR), CR with incomplete count recovery (CRi), and cytogenetic complete remission (CCyR) to induction chemotherapy.
II. To determine the overall survival, event-free survival, and remission duration in patients treated on this study.
III. To describe the frequency and severity of adverse events for patients treated on this study.
IV. To describe the interaction of pre-treatment disease and patient characteristics including morphology, cytogenetics, immunophenotype, molecular genetic features, white blood cell (WBC) count and hemogram, and performance status on clinical outcomes.
V. To assess FLT3 ligand concentrations and FLT3 plasma inhibitory activity during treatment and determine the relationship to clinical outcomes.
VI. To describe the interaction of FLT3 mutation type (tyrosine kinase domain [TKD] vs. ITD) and allelic ratio on clinical outcomes.
VII. To characterize geriatric assessment measures in the context of a treatment trial for AML defined by: the observed distribution and number of missing values for each measurement.
VIII. To identify specific geriatric assessment measures which are independently associated with overall survival (OS), 30-day treatment-related mortality and key quality of life outcomes (number of days hospitalized, number of oncology clinic visits, admission to a nursing facility) in patients receiving induction chemotherapy for AML.
IX. To explore the impact of induction chemotherapy on physical, cognitive, psychosocial factors.
INDUCTION THERAPY: Patients receive daunorubicin hydrochloride intravenously (IV) on days 1-3, cytarabine IV continuously on days 1-7, and sorafenib tosylate orally (PO) twice daily (BID) on days 1-7. Patients then undergo a bone marrow aspirate or biopsy on day 14.
Patients with persistent disease undergo a second remission induction therapy comprising daunorubicin hydrochloride IV on days 1-2, cytarabine IV continuously on days 1-5, and sorafenib tosylate PO BID on days 1-7. Patients who achieve complete response (CR)* proceed to consolidation therapy.
CONSOLIDATION THERAPY: Patients** receive cytarabine IV over 3 hours on days 1-5 and sorafenib tosylate PO BID on days 1-28. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with continued CR proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive sorafenib tosylate PO BID on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
NOTE: *Patients who achieve CR and who are eligible for hematopoietic stem cell transplant (HSCT) are encouraged to enroll in Cancer and Leukemia Group B (CALGB) 100103. Patients in CR who are unable or unwilling to undergo HSCT receive two courses of remission consolidation therapy.
NOTE: ** Patients in CR/complete remission with incomplete count recovery (CRi) who are unable or unwilling to complete remission consolidation therapy may proceed directly to maintenance therapy after consulting with the CALGB study chair.
After completion of study therapy, patients are followed up every 2 months for 2 years, every 3 months for 2 years, and then yearly for a maximum of 10 years.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||54 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study Incorporating Sorafenib (NSC 724772) Into the Therapy of Patients ≥ 60 Years of Age With FLT3 Mutated Acute Myeloid Leukemia|
|Study Start Date :||April 2011|
|Primary Completion Date :||October 2014|
Experimental: Treatment (daunorubicin, cytarabine, sorafenib tosylate)
INDUCTION THERAPY: Daunorubicin hydrochloride 60 mg/m^2/day by IV push or short IV on days 1-3, cytarabine 100 mg/m^2/day by continuous IV on days 1-7, and sorafenib tosylate 400mg orally every 12 hours on days 1-7.
CONSOLIDATION THERAPY - Every 28 days for 2 cycles: Cytarabine 2 g/m^2/day by IV on days 1-5 and sorafenib tosylate 400 mg orally every 12 hours on days 1-28.
MAINTENANCE - Every 28 days for up to 12 cycles: Sorafenib tosylate 400 mg orally every 12 hours on days 1-28.
Drug: Daunorubicin Hydrochloride
Other Names:Drug: Sorafenib Tosylate
Other Names:Drug: Cytarabine
Other Names:Procedure: Bone Marrow Aspiration
Undergo bone marrow aspirateProcedure: Biopsy
Other Name: BxOther: Laboratory Biomarker Analysis
Correlative studiesOther: Quality-of-Life Assessment
Other Name: Quality of Life AssessmentOther: Questionnaire Administration
- Overall Survival (OS) Rate [ Time Frame: 1 year ]Percentage of patients who were alive at 1 year. The analysis was split between patients with having a FLT3 (FMS-like tyrosine kinase-3) ITD (internal tandem duplication) or TKD (tyrosine kinase domain) mutation. The FLT3 mutation testing at baseline was performed centrally for all patients.
- OS [ Time Frame: Time from registration to death (up to 10 years) ]OS was defined as the time from registration to death of any cause. Surviving patients were censored at the date of last follow-up. The median OS with 95% confidence interval (CI) was estimated using the Kaplan Meier method.
- Event-free Survival [ Time Frame: Time from registration to death or relapse (up to 10 years) ]Event-free survival (EFS) was defined as the time for registration to failure to achieve CR during induction, relapse or death. Participants without events were censored at date of last follow-up. The median EFS with 95% CI was estimated using the Kaplan Meier method.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01253070
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|Principal Investigator:||Geoffrey Uy||Alliance for Clinical Trials in Oncology|