A Phase 2 Study of Decitabine in Combination With Midostaurin (PKC412) for Elderly Patients With Newly Diagnosed FLT3-ITD/TKD Positive Acute Myeloid Leukemia
Overview
- Phase
- Phase 2
- Intervention
- Decitabine
- Conditions
- Acute Myeloid Leukemia (AML) With Multilineage Dysplasia Following Myelodysplastic Syndrome, in Adults
- Sponsor
- David Iberri
- Enrollment
- 13
- Locations
- 1
- Primary Endpoint
- Complete Remission (CR) Rate
- Status
- Terminated
- Last Updated
- 7 years ago
Overview
Brief Summary
This phase 2 study evaluates the sequential combination of decitabine then midostaurin for the treatment of newly-diagnosed acute myeloid leukemia (AML) in older patients.
Detailed Description
Treatment with decitabine, a cytidine analog, then midostaurin, a multi-target protein kinase inhibitor (PKI), may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Investigators
David Iberri
Clinical Assistant Professor
Stanford University
Eligibility Criteria
Inclusion Criteria
- •Newly-diagnosed acute myeloid leukemia (AML) per the World Health Organization \[WHO\] 2008 classification \[except t (15; 17)\], including:
- •De novo AML
- •Secondary AML
- •Secondary AML arising from previously-diagnosed myelodysplastic syndromes (MDS) treated with deoxyribonucleic acid (DNA) methyltransferase inhibitor (DNMTi) (ie, decitabine or azacitidine)
- •FLT3-ITD mutation confirmed in bone marrow aspirate
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN)
- •Serum bilirubin ≤ 2.5 ULN
- •Serum creatinine ≤ 1.5 mg/dL and/or creatinine clearance ≥ 50 mL/min
- •Ejection fraction ≥ 50% by echocardiogram
Exclusion Criteria
- •Receiving concomitant treatment with other anti-neoplastic agents (EXCEPTION: hydroxyurea). Prior treatment with DNMTi therapy (ie, decitabine or azacitidine) for MDS is allowed
- •Received anti-neoplastic treatment within 4 weeks prior to enrollment (EXCEPTION: hydroxyurea)
- •Received any surgical procedure, excluding central venous catheter placement or other minor procedures (eg, skin biopsy) within 14 days of study day 1
- •Received any investigational agent within 4 weeks prior to enrollment
- •Previous or current history of a myeloproliferative disease
- •Known active central nervous system (CNS) malignancy
- •Any other known disease (except carcinoma in-situ), concurrent severe and/or uncontrolled medical condition which could compromise participation in the study (eg, uncontrolled diabetes; cardiovascular disease including congestive heart failure; myocardial infarction within 6 months with poorly controlled hypertension; chronic renal disease; active uncontrolled infection)
- •Active opportunistic infection or treatment for opportunistic infection within 4 weeks of first day of study drug dosing
- •Known confirmed diagnosis of human immunodeficiency virus (HIV) infection or active viral hepatitis
- •Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of midostaurin
Arms & Interventions
Decitabine, then midostaurin
INDUCTION THERAPY Subjects receive decitabine intravenously (IV) over 1 hour on days 1 to 10 and midostaurin orally (PO) twice daily (BID) on days 11 to 28. Treatment repeats every 28 days until documented bone marrow response is achieved or for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients achieving documented bone marrow response by course 6 continue treatment with induction therapy; patients achieving response after course 6 proceed to post-remission therapy. POST-REMISSION THERAPY Subjects receive decitabine IV over 1 hour on days 1 to 5 and midostaurin PO BID on days 6 to 28. Treatment repeats every 28 days for up to 12 courses (including induction therapy) in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for up to 1 year.
Intervention: Decitabine
Decitabine, then midostaurin
INDUCTION THERAPY Subjects receive decitabine intravenously (IV) over 1 hour on days 1 to 10 and midostaurin orally (PO) twice daily (BID) on days 11 to 28. Treatment repeats every 28 days until documented bone marrow response is achieved or for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients achieving documented bone marrow response by course 6 continue treatment with induction therapy; patients achieving response after course 6 proceed to post-remission therapy. POST-REMISSION THERAPY Subjects receive decitabine IV over 1 hour on days 1 to 5 and midostaurin PO BID on days 6 to 28. Treatment repeats every 28 days for up to 12 courses (including induction therapy) in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for up to 1 year.
Intervention: Midostaurin
Outcomes
Primary Outcomes
Complete Remission (CR) Rate
Time Frame: Up to 1 year
The complete remission (CR) rate, or complete response rate, is reported as the sum and proportion of participants that achieved CR or CR with incomplete blood count recovery (CRi), within 12 months of starting midostaurin treatment. * Complete remission (CR): Bone marrow blasts \< 5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count (ANC) \> 1000/μL; platelet count \> 100,000/μL; independence of red cell transfusions. * CR with incomplete recovery (CRi): All CR criteria except for ANC \< 1000/μL or platelet count \< 100,000/μL. * Partial remission (PR): All hematologic criteria of CR; except decrease of bone marrow blast percentage to 5% to 25%; and decrease of pretreatment bone marrow blast percentage by at least 50%.
Secondary Outcomes
- Overall Response Rate (ORR)(up to 1 year)
- Progression-free Survival (PFS)(Up to 2 years)
- Median Duration of Response (DoR)(Up to 1 year)
- Overall Survival (OS)(Up to 2 years)