iCare4: Genomic Signatures With Midostaurin in Acute Myeloid Leukemia (UF-HEM-004)

NCT03207334 | Withdrawn Phase 2 DMC FDA Drug

• 3 other identifiers: UF-HEM-004CPKC412AUS61TIRB201701934
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label, single arm study of midostaurin in patients with relapsed or refractory AML.

Conditions

Acute Myeloid Leukemia

Keywords

acute myeloid leukemia; genomic signatures; midostaurin; relapsed; refractory; PKC412

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  Compare the progression free survival of patients receiving midostaurin and cytarabine to that historically achieved in patients receiving cytarabine alone

  Up to 6 months

Secondary Outcomes (3)

• Number of participants with treatment-related adverse events as assessed by National Cancer Institute (NCI) Common Terminology for Adverse Events(CTCAE) v4.0

  Up to 2.5 years

• Overall survival

  Up to 3.5 years

• Morphologic response rate

  Up to 6 months

Study Arms (1)

Midostaurin and Cytarabine

EXPERIMENTAL

Treatment will consist of 3 phases: induction (a 28-42 day cycle), followed by consolidation (up to 4 cycles). Each cycle in the consolidation phase will last 28 days. Subjects will proceed from one phase to the next if they have achieved or maintained a complete remission or complete remission with incomplete blood count recovery by International Working Group 2003 response criteria. Patients may receive a allogeneic hematopoietic stem cell transplant between the end of the induction phase.

Drug: Midostaurin; Drug: Cytarabine

Interventions

Midostaurin DRUG

Induction Phase: 50 mg orally twice daily beginning on day 7 and ending 48 hours prior to beginning the consolidation phase Consolidation Phase: 50 mg orally twice daily beginning on Day 6 and ending 48 hours prior to either the start of the next cycle or beginning conditioning therapy for allogenic stem cell transplant.

Also known as: PKC412, Rydapt

Midostaurin and Cytarabine

Cytarabine DRUG

Induction Phase: 3 g/m2 (patients 18-65 years old) or 1 g/m2 (patients \> 65 years old or those with co-morbidities precluding a higher dose) by vein over 3 hours every 12 hours on Days 1-6. Consolidation Phase: 3 g/m2 (patients 18-65 years old) or 1 g/m2 (patients \> 65 years old or those with co-morbidities precluding a higher dose) by vein over 3 hours every 12 hours on Days 1, 3, and 5 of each cycle.

Also known as: Depocyt

Midostaurin and Cytarabine

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent obtained from the subject prior to registration on the study and the ability for the subject to adhere to the study visit schedule and all the study-related procedures.
• A diagnosis of relapsed or refractory AML. For the purpose of this study, refractory AML is defined as failure to achieve CR after one cycle of induction chemotherapy and relapsed AML is defined as any evidence of disease recurrence after achieving CR of any duration.
• Both males and females ≥ eighteen years of age
• Karnofsky Performance Status of ≥ 70% or Eastern Cooperative Oncology Group (ECOG) performance status \< 2 (unless poor performance status is related to the disease).
• Adequate organ function defined as:
• AST and ALT \< 2.5 times the upper limit of normal (ULN),
• Serum bilirubin \< 2.5 x ULN, and
• Serum creatinine \< 1.5 mg/dL or creatinine clearance \> 50 mL/min.
• Laboratory values can be outside of this range if secondary to AML disease.
• An ejection fraction of \> 45% confirmed by echocardiogram.
• Life expectancy of greater than one month.
• Subjects who previously received midostaurin are allowed if the last dose of midostaurin was given ≥ six months prior to disease relapse.
• Females who are non-pregnant and non-nursing.
• Females of reproductive age and males must agree to avoid getting pregnant or to father a child while on therapy and for five months after the last dose of chemotherapy.
• Women of child-bearing potential (WOCBP) must either agree to continued abstinence from heterosexual intercourse or begin one of the following acceptable methods of birth control: IUD, tubal ligation, or partner must use a latex condom during any sexual contact, even if the partner has undergone a successful vasectomy. Hormonal contraception is an inadequate method of birth control.

You may not qualify if:

• Age ≥ of seventy-six years.
• Subjects with the inability to swallow oral medications.
• Clinical evidence of active CNS leukemia.
• A medical history of receiving an allogeneic hematopoietic stem cell transplantation (HSCT).
• Subjects must not have any uncontrolled or intercurrent illness including, but not limited to,
• ongoing or active infection,
• symptomatic congestive heart failure,
• unstable angina pectoris,
• cardiac arrhythmia,
• myocardial infarction within three months,
• poorly controlled hypertension,
• uncontrolled diabetes, or psychiatric illness/social situation that would limit compliance with protocol requirements.
• Females or males of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least five months after the last dose of chemotherapy.
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of PKC412.
• Previous therapy with midostaurin within six months prior to relapse.

Sponsors & Collaborators

• University of Florida: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

University of Florida

Gainesville, Florida, 32610, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Recurrence

Interventions

midostaurin; Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Maxim Norkin, MD, PhD

  University of Florida

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: All patients will receive midostaurin and cytarabine.

Study Record Dates

• First Submitted: June 26, 2017
• First Posted: July 2, 2017
• Study Start: November 1, 2018
• Primary Completion: January 1, 2021
• Study Completion: January 1, 2022
• Last Updated: October 22, 2018

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)