Midostaurin and Decitabine in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia and FLT3 Mutation

NCT02634827 | Terminated Phase 2 Results DMC

• 3 other identifiers: MC1483NCI-2015-02107P30CA015083
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well midostaurin and decitabine work in treating older patients with newly diagnosed acute myeloid leukemia and FLT3 mutations. Midostaurin and decitabine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Conditions

Acute Myeloid Leukemia With FLT3/ITD Mutation; Acute Myeloid Leukemia With Gene Mutations; FLT3 Tyrosine Kinase Domain Point Mutation; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Proportion of Complete Responses to Therapy, Where a Success is Defined as a CR or CRi as the Objective Status

  The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Exact binomial confidence intervals for the true success proportion will be calculated.

  Up to 2 years

Secondary Outcomes (5)

• Duration of Complete Response, Defined for All Evaluable Patients Who Have Achieved a CR or CRi as the Date at Which the Patient's Objective Status is First Noted to be a CR or CRi to the Earliest Date Relapse is Documented

  Up to 2 year

• Incidence of Adverse Events, Graded According to the NCI CTCAE Version 4.0

  Up to 2 years

• OS

  Time from registration to death due to any cause, assessed up to 2 years

• Overall Response Rate, Estimated by the Total Number of Complete or Partial Responses (CR, CRi, Morphologic Leukemia-free State, or PR) Divided by the Total Number of Evaluable Patients

  Up to 2 years

• PFS

  Time from registration to the time of relapse or death due to any cause, assessed up to 2 years

Other Outcomes (2)

• FLT3 Mutation by ITD vs. TKD vs. Both, Assessed by Polymerase Chain Reaction (PCR), Western Blot, and Flow Cytometry

  Up to day 1 of course 9

• Minimal Residual Disease (MRD) Status, Assessed by PCR for FLT3 Mutation (if FLT3 is Repeated) or Flow Cytometry

  Up to day 1 of course 9

Study Arms (1)

Treatment (decitabine, midostaurin)

EXPERIMENTAL

Patients receive decitabine intravenously (IV) over 1 hour on days 1-5 and midostaurin orally (PO) twice daily (BID) on days 8-21 of courses 1 and 2, and on days 1-28 of each subsequent course. Patients failing to achieve complete response (CR)/complete response with incomplete recovery (CRi)/partial response (PR)/morphologic leukemia-free state by end of course 2 receive midostaurin PO BID on days 1-28. Patients achieving CR/CRi/PR/morphologic leukemia-free state by end of course 8 may continue on current regimen. Patients failing to achieve a CR/CRi/PR/ morphologic leukemia-free state in bone marrow blasts by end of course 8 go to event monitoring. Treatment repeats every 28 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.

Drug: Decitabine; Other: Laboratory Biomarker Analysis; Drug: Midostaurin

Interventions

Decitabine DRUG

Given IV

Also known as: 5-Aza-2'-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine, Dezocitidine

Treatment (decitabine, midostaurin)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (decitabine, midostaurin)

Midostaurin DRUG

Given PO

Also known as: CGP 41251, CGP41251, N-Benzoyl-Staurosporine, N-Benzoylstaurosporine, PKC-412, PKC412

Treatment (decitabine, midostaurin)

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Unfit for chemotherapy based on investigator assessment or patient not willing to receive intensive induction as advised by investigator
• Untreated, histological confirmed acute myeloid leukemia (AML) based on World Health Organization (WHO) 2008 criteria with either/or both:
• FLT3 ITD mutation
• FLT3 TKD mutation
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, 2 or 3
• Serum amylase and lipase =\< 1.5 x upper limit of normal (ULN)
• Total bilirubin =\< 1.5 x ULN (does not apply to patients with isolated hyperbilirubinemia \[e.g., Gilbert's disease\], in that case direct bilirubin should be =\< 2 x ULN)
• Alkaline phosphatase =\< 3 x ULN
• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 2.5 x ULN
• Creatinine =\< 2 x ULN
• Negative pregnancy test done =\< 7 days prior to registration, for women of childbearing potential only
• Provide informed written consent
• Willing to return to consenting Mayo Clinic (Mayo Clinic's campus in Rochester), for follow-up during the Active Monitoring Phase of the study
• Willing to provide bone marrow aspirate and blood samples for correlative research purposes

You may not qualify if:

• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 3 months after treatment completion
• Highly effective contraception methods include:
• Total abstinence (when this is in line with the preferred and usual lifestyle of the subject; NOTE: periodic abstinence \[e.g., calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception)
• Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
• Male sterilization (at least 6 months prior to screening); NOTE: for female subjects on the study the vasectomized male partner should be the sole partner for that subject
• Combination of any two of the following (a+b or a+c, or b+c):
• a) Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate \< 1%), for example hormone vaginal ring or transdermal hormone contraception
• b) Placement of an intrauterine device (IUD) or intrauterine system (IUS)
• c) Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository
• NOTE:
• In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment
• Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) OR
• Sexually active males unless they use a condom during intercourse while taking drug and for 5 months after stopping midostaurin medication
• NOTE:
• They should not father a child in this period

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Interventions

Decitabine; Injections; midostaurin

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Drug Administration Routes; Drug Therapy; Therapeutics

Results Point of Contact

• Title: Aref Al-Kali, MD
• Organization: Mayo Clinic

AlKali.Aref@mayo.edu

507-538-0871

Study Officials

• Aref Al-Kali

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2015
• First Posted: December 18, 2015
• Study Start: December 30, 2015
• Primary Completion: March 18, 2017
• Study Completion: June 12, 2018
• Last Updated: August 7, 2019
• Results First Posted: August 7, 2019

Record last verified: 2018-06

Locations

US (1)