Pacritinib and Chemotherapy in Treating Patients With Acute Myeloid Leukemia and FLT3 Mutations

NCT02323607 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: OSU-14169NCI-2014-02436
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of pacritinib when given together with chemotherapy in treating patients with acute myeloid leukemia that have an abnormal change (mutation) in the fms-related tyrosine kinase 3 (FLT3) gene. Pacritinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cytarabine, daunorubicin hydrochloride, and decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving pacritinib and chemotherapy may be a better treatment for acute myeloid leukemia with FLT3 mutations.

Conditions

Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Therapy-Related Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• MTD of pacritinib defined as the highest safely tolerated dose where, at most, one patient experiences DLT in 6 evaluable patients, with the next higher dose having at least 2 patients who experience DLT

  Assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. Toxicities will be tabulated by type and grade and displayed in summary form. Further, all adverse event data that are graded as 3, 4, or 5 and classified as either unrelated or unlikely to be related to study treatment will be reviewed for completeness.

  28 days

Secondary Outcomes (2)

• Clinical response according to International Working Group criteria

  Up to at least 30 days post-treatment

• Duration of response

  Up to at least 30 days post-treatment

Other Outcomes (2)

• Change in FLT3 and JAK2 expression

  Baseline to up to at least 30 days post-treatment

• Change in various genes/microRNA

  Baseline to up to at least 30 days post-treatment

Study Arms (2)

Cohort A (pacritinib, cytarabine, daunorubicin hydrochloride)

EXPERIMENTAL

INDUCTION: Patients receive pacritinib PO on days 1-21, cytarabine IV every 24 hours on days 5-11, and daunorubicin hydrochloride IV every 24 hours on days 5-7. Treatment repeats every 28 days for 1-2 courses in the absence of disease progression or unacceptable toxicity.

Drug: Pacritinib; Drug: Cytarabine; Drug: Daunorubicin Hydrochloride; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Cohort B (pacritinib, decitabine)

EXPERIMENTAL

INDUCTION: Patients receive pacritinib PO on days 1-21 and decitabine IV every 24 hours on days 5-14. Treatment repeats every 28 days for 2-4 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients achieving CR will proceed with transplant evaluation (if appropriate). Transplant-ineligible patients will receive maintenance courses of pacritinib PO on days 1-21 and decitabine IV over 1 hour daily on days 1-5. Maintenance courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Pacritinib; Drug: Decitabine; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Interventions

Pacritinib DRUG

Given PO

Also known as: Oral JAK2 Inhibitor SB1518, SB1518

Cohort A (pacritinib, cytarabine, daunorubicin hydrochloride); Cohort B (pacritinib, decitabine)

Cytarabine DRUG

Given IV

Also known as: CHX-3311, U-19920

Cohort A (pacritinib, cytarabine, daunorubicin hydrochloride)

Daunorubicin Hydrochloride DRUG

Given IV

Also known as: DNM, DNR, DRB

Cohort A (pacritinib, cytarabine, daunorubicin hydrochloride)

Decitabine DRUG

Given IV

Also known as: 5AZA, DAC

Cohort B (pacritinib, decitabine)

Laboratory Biomarker Analysis OTHER

Correlative studies

Cohort A (pacritinib, cytarabine, daunorubicin hydrochloride); Cohort B (pacritinib, decitabine)

Pharmacological Study OTHER

Correlative studies

Also known as: pharmacological studies

Cohort A (pacritinib, cytarabine, daunorubicin hydrochloride); Cohort B (pacritinib, decitabine)

Eligibility Criteria

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

You may qualify if:

• Patients with AML and the presence of FLT3 mutation
• Patients with secondary AML or therapy related disease (t-AML) are eligible
• If the patient has co-morbid medical illness, life expectancy attributed to this must be greater than 6 months
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• Total bilirubin \< 2.0mg/dL unless due to Gilbert's disease
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) \< 2.5 X institutional upper limit of normal
• Creatinine (Cr) clearance \> 50 mL/min by Cockcroft-Gault calculation
• New York Heart Association (NYHA) congestive heart failure (CHF) class II or better
• Cardiac ejection fraction \>= 50% for Arm A, \>= 40% for Arm B
• Female patients of child-bearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening, and male patients must use an effective barrier method of contraception if sexually active with a female of child-bearing potential; acceptable methods of contraception are condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal; for both male and female patients, effective methods of contraception must be used throughout the study and for three months following the last dose
• Ability to understand and willingness to sign the written informed consent document
• Human immunodeficiency virus (HIV) infection without history of acquired immune deficiency syndrome (AIDS) and sufficiently high cluster of differentiation (CD)4 cells (\> 400/mm\^3) and low HIV viral loads (\< 30,000 copies/ml plasma) not requiring anti-HIV therapy are eligible

You may not qualify if:

• Patients with core-binding factor AML (inv\[16\], t\[8;21\]) or t(15;17)
• Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study; treatment with hydroxyurea is permitted during cycle 1 to maintain white blood cell (WBC) \< 40,000/uL
• Patients receiving any other investigational agents or patients that have received other investigational agents within 14 days of enrollment
• Patients with active central nervous system (CNS) malignancy
• Major surgery within 2 weeks before day 1
• Uncontrolled active infection; patients with infection requiring parenteral antibiotics are eligible if the infection is controlled
• Patients with significantly diseased or obstructed gastrointestinal tract
• Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure (New York Heart Association \[NYHA\] class III or IV), unstable angina pectoris, myocardial infarction within 6 months prior to enrollment, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
• Patients with serious medical or psychiatric illness likely to interfere with participation in this clinical study
• Pregnant women or women who are breastfeeding are excluded from this study; confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening; pregnancy testing is not required for post-menopausal or surgically sterilized women
• Patients with advanced malignant solid tumors
• Patients who are not able to swallow capsules or tablets
• Patients with baseline corrected QT (QTc) \> 500 ms

Sponsors & Collaborators

• Bhavana Bhatnagar: lead
• CTI BioPharma: collaborator

Study Sites (1)

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Related Links

• The Jamesline

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,26-triazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene; Cytarabine; Daunorubicin; Dichlororibofuranosylbenzimidazole; Decitabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Ribonucleosides; Azacitidine; Aza Compounds

Study Officials

• Bhavana Bhatnagar, DO

  Arthur G. James Cancer Hospital and Solove Research Institute at Wexner Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 18, 2014
• First Posted: December 23, 2014
• Study Start: January 12, 2016
• Primary Completion: July 12, 2018
• Study Completion: July 12, 2018
• Last Updated: January 25, 2019

Record last verified: 2019-01

Locations

US (1)