Pacritinib Combined With Decitabine or Cytarabine in Older Patients With AML

NCT02532010 | Terminated Phase 2 Results DMC

• 1 other identifier: 1403014921
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to see if a medicine called pacritinib is both safe and effective as a study intervention for patients with AML in combination with either decitabine or cytarabine. Pacritinib is an experimental drug that is being studied to treat acute myeloid leukemia (AML). Decitabine and cytarabine are both FDA approved drugs that are used in treatment of AML. Pacritinib is being tested in clinical trials and has not been submitted to the U.S. Food and Drug Administration (FDA) for approval for any indications. Pacritinib is a drug that is designed to slow down the growth of leukemic cells.

Conditions

Acute Myeloid Leukemia (AML)

Outcome Measures

Primary Outcomes (1)

• Complete Remission Rate

  Complete remission rate is defined as number of subjects with complete remission according to the IWG criteria, which is defined by presence of \<5 percent of blasts in the bone marrow, absence of blasts with Auer rods, absence of extramedullary disease, absolute neutrophil count \>1.0 x 109/L (1000/µL); platelet count \>100 x 109/L (100,000/µL); independence of red cell transfusions.

  6 months

Secondary Outcomes (6)

• Overall Survival

  2 years

• Overall Remission Rate

  6 months

• Relapse-free Survival

  From date of complete remission until either AML relapse or death from any cause, whichever came first, assessed throughout the study period up to 2 years

• Event-free Survival

  Time from entry on study until time at which there is treatment failure, AML relapse, or death from any cause, assessed throughout the study period up to 2 years

• Time to Complete Response

  From entry on study until complete remission, assessed throughout the study period up to 2 years

Study Arms (2)

Arm A: Pacritinib and Decitabine

ACTIVE COMPARATOR

Arm A: Each cycle: Decitabine 20mg/m2 intravenous daily for 10 days combined with ongoing pacritinib 200 mg twice daily.

Drug: Pacritinib; Drug: Decitabine

Arm B: Pacritinib and Cytarabine

ACTIVE COMPARATOR

Arm B: Each cycle: Cytarabine 20mg subcutaneous twice daily for 10 days combined with ongoing pacritinib 200mg twice daily.

Drug: Pacritinib; Drug: Cytarabine

Interventions

Pacritinib DRUG

Pacritinib is a novel Janus kinase 2-fms-like receptor tyrosine kinase 3 (JAK2-FLT3) inhibitor that has shown promising antitumor activity. Pacritinib is a potent inhibitor of JAK2 and FLT3 kinase activities (50% inhibitory concentration (IC50) = 23 nanomolar (nM)and 22 nM, respectively). The drug also inhibits cellular proliferation in human leukemia and lymphoma cell lines selected for their dependence on either of the target kinases. Consistent with these activities, exposure to pacritinib resulted in the reduction of phos-JAK2, phos-STAT3 or phos-STAT5 in the relevant cell lines. Unlike some JAK2 inhibitors, pacritinib does not inhibit Janus kinase 1 (JAK1).

Also known as: SB1518

Arm A: Pacritinib and Decitabine; Arm B: Pacritinib and Cytarabine

Decitabine DRUG

Commercial drug: For each cycle Decitabine 20mg/m2 intravenous daily for 10 days combined with ongoing pacritinib 200 mg twice daily.

Also known as: Dacogen

Arm A: Pacritinib and Decitabine

Cytarabine DRUG

Commercial drug: For each cycle Cytarabine 20mg subcutaneous twice daily for 10 days combined with ongoing pacritinib 200mg twice daily.

Also known as: Cytosar-U, Tarabine PFS, Cytosar

Arm B: Pacritinib and Cytarabine

Eligibility Criteria

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

You may qualify if:

• Patient has unequivocal pathologic diagnosis of AML (≥ 20% blasts in the bone marrow based on World Health Organization (WHO) criteria), excluding acute promyelocytic leukemia t(15;17)(q22;q12); Promyelocytic leukemia gene (PML)- retinoic acid receptor alpha (RARA)
• Age ≥ 65 years old
• No prior treatment for AML except:
• Emergency leukapheresis
• Emergency treatment for hyperleukocytosis with hydroxyurea
• Cranial radiotherapy (RT) for Central Nervous System (CNS) leukostasis (one dose only)
• Growth factor/cytokine support
• AML patients with therapy-related myeloid neoplasms are eligible if they have not received radiation therapy or chemotherapy (not including hormonal therapy) for their primary malignancy or disorder for ≥ 6 months. Hydroxyurea may be used at the investigator's discretion up to the first 28 days on Cycle 1 to maintain WBC \<30,000/µl.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Subjects must have adequate hepatic and renal function
• Female subject of child-bearing potential and male subjects with female partners of reproductive potential must use acceptable contraceptive methods
• Able to understand and to provide written informed consent
• Able to comply with all study procedures during the study including all visits and tests
• Willing to adhere to the prohibitions and restrictions specified in this protocol
• Patient must sign an informed consent form (ICF)

You may not qualify if:

• Prior treatment with decitabine
• Prior treatment with cytarabine
• Prior treatment with pacritinib
• Presence of serious illness, medical condition, or other medical history, involving the heart, kidney, liver, or other organ system, including abnormal laboratory parameters, which, in the opinion of the Investigator, would be likely to interfere with a subject's participation in the study or with the interpretation of the results.
• Active, uncontrolled, clinically significant infection(s)
• Have other active malignancies (excluding other myeloid hematologic malignancies) or other malignancies within 12 months before enrollment, except curatively treated non-melanoma skin cancer, cervical intraepithelial neoplasia, organ-confined or treated non-metastatic prostate cancer with negative prostate-specific antigen, in situ breast carcinoma after complete surgical resection, or superficial transitional cell bladder carcinoma
• Are receiving any other investigational therapy or protocol-prohibited therapy
• Any prior or co-existing medical condition that in the Investigator's judgment will substantially increase the risk associated with the subject's participation in the study
• Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures
• Any gastrointestinal (GI) or metabolic condition that could interfere with absorption of oral medication
• Inflammatory or chronic functional bowel disorder, such as Crohn's disease, inflammatory bowel disease, chronic diarrhea
• Clinically symptomatic and uncontrolled cardiovascular disease
• History of any of the following within 6 months: myocardial infarction, severe/unstable angina, or symptomatic congestive heart failure
• New York Heart Association Class III or IV congestive heart failure

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead

Study Sites (1)

Weill Cornell Medical College

New York, New York, 10021, United States

Location

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; Decitabine; Cytarabine

Condition Hierarchy (Ancestors)

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

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; Arabinonucleosides

Results Point of Contact

• Title: Dr. Sangmin Lee
• Organization: Weill Cornell Medicine

sal9053@med.cornell.edu

646-962-2700

Study Officials

• SangMin Lee, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2015
• First Posted: August 25, 2015
• Study Start: June 15, 2015
• Primary Completion: February 9, 2016
• Study Completion: October 24, 2017
• Last Updated: June 15, 2018
• Results First Posted: June 15, 2018

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will share

Locations

US (1)