Pacritinib for Patients With Lower-Risk Myelodysplastic Syndromes (MDS)

NCT02469415 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 2013-0224NCI-2015-01306
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if pacritinib, either alone or in combination with azacitidine or decitabine, can help to control MDS. The safety of this drug and drug combination will also be studied.

Conditions

Leukemia

Keywords

Leukemia; Myelodysplastic syndromes; MDS; Lower-risk; Pacritinib; 5-azacitidine; Azacitidine; 5-azacytidine; Vidaza; 5-AZC; AZA-CR; Ladakamycin; NSC-102816; Azacytidine; Decitabine; Dacogen

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  The primary efficacy outcome of both parts is the overall response rate (ORR) based mainly on hematologic improvement defined by (International Working Group) IWG-2006 criteria, and which also includes complete remission (CR), partial remission (PR) and marrow complete remission.

  28 days

Study Arms (1)

Pacritinib + Azacitidine or Decitabine

EXPERIMENTAL

Part 1: Pacritinib 200 mg taken by mouth twice daily. Study cycles administered every 28 days. Part 2: After 4 cycles of treatment, Pacritinib combined with 5-azacitidine or Decitabine. Pacritinib decreased to 200 mg in morning and 100 mg in evening for first cycle of combined therapy with Pacritinib increased to 200 mg twice a day on subsequent cycles of combined therapy. Those with disease progression prior to 4 cycles of Pacritinib may initiate Pacritinib + HMA study portion prior to completion of 4 cycles. Starting dose of either 5-azacitidine 75 mg/m2 by vein (IV) or Decitabine 20 mg/m2 IVon Days 1 - 5 of Cycles 5 and beyond.

Drug: Pacritinib; Drug: 5-azacitidine; Drug: Decitabine

Interventions

Pacritinib DRUG

Part 1: Pacritinib 200 mg taken by mouth twice daily. Part 2: Pacritinib dose decreased to 200 mg in the morning and 100 mg in the evening for the first cycle of combined therapy. If no toxicity is observed in first cycle of combined therapy, Pacritinib dose may be increased to 200 mg twice a day on subsequent cycles of combined therapy.

Pacritinib + Azacitidine or Decitabine

5-azacitidine DRUG

Part 2 Starting Dose of 5-azacitidine: 75 mg/m2 by vein on Days 1 - 5 of Cycles 5 and beyond.

Also known as: Azacitidine, 5-azacytidine, 5-aza, Vidaza, 5-AZC, AZA-CR, Ladakamycin, NSC-102816, Azacytidine

Pacritinib + Azacitidine or Decitabine

Decitabine DRUG

Part 2 Starting Dose of Decitabine: 20 mg/m2 by vein on on Days 1 - 7 of Cycles 5 and beyond.

Also known as: Dacogen

Pacritinib + Azacitidine or Decitabine

Eligibility Criteria

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

You may qualify if:

• Signed informed consent indicating that patients are aware of the investigational nature of this study, in keeping with the policies of MD Anderson Cancer Center (MDACC), must be obtained prior to any study specific procedures.
• Patients with a histologically confirmed diagnosis of MDS by World Health Organization (WHO) classification, and lower-risk MDS as defined by the IPSS classification (Low or Int-1 disease) or R-IPSS classification (Very Low or Low) are eligible. Patients with MDS/MPD overlap syndromes including CMML are also eligible if they have Low or Int-1 disease per IPSS. Patients may have received MDS-directed therapy (i.e. lenalidomide), although patients with prior exposure to hypomethylating agents (e.g. 5-azacitidine or decitabine) are not eligible.
• The interval from prior treatment to time of study drug administration is at least 1 week (except for hydroxyurea or steroid therapy) with recovery from all prior therapy-related toxicities
• Age \>/= 18 years old.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Adequate liver function, as evidence by serum bilirubin \</= 2x the laboratory normal range (except for patients with Gilbert's Disease) or an aspartate aminotransferase (AST) or alanine aminotransferase (ALT) of \</= 2.5x the upper limit of normal (ULN) or \</= 5x ULN if hepatic disease involvement is present as determined by the investigator.
• Serum creatinine (Cr) \</= 2x ULN or 24-hour creatinine clearance \>/=50 ml/min
• Subjects of reproductive potential must agree to the use of acceptable contraceptive methods for the duration of the time on study and a further 6 months after completion of treatment. Women of childbearing potential must have a negative blood or urine pregnancy test within 72 hours of start of treatment.

You may not qualify if:

• Subjects with any prior exposure to the hypomethylating agents (5-azacitidine or decitabine) are excluded.
• Subjects with any prior exposure to JAK2 inhibitor therapy (i.e. ruxolitinib or prior pacritinib therapy) are excluded.
• Any prior or coexisting 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.
• Active uncontrolled serious infection or sepsis at study enrollment. Patients receiving antibiotics for infections that are under control may be included in the study.
• Gastrointestinal disorders that may significantly interfere with absorption of study drug.
• Subjects have received potent CYP3A inhibitors within 7 days prior to the initiation of study treatment.
• History of myocardial infarction, severe/unstable angina, or symptomatic congestive heart failure (New York Heart Failure (NYHA) Class III or IV congestive heart failure) within 6 months prior to study enrollment or Left ventricular ejection fraction (LVEF) \<50%
• Impaired cardiac function including ongoing cardiac dysrhythmias of Grade \> 2, ejection fraction \< 50%, atrial fibrillation of any grade, or QTc prolongation \> 450 ms, or other factors that increase the risk of QT prolongation (i.e. family history of long QT interval syndrome, hypokalemia defined as serum potassium \< 3.0 mEq/L)
• Diagnosis of other malignancies within the last 3 years other than curatively treated non-melanoma skin cancer, carcinoma in situ of the cervix, organ-confined or treated non-metastatic prostate cancer, in situ breast carcinoma after complete surgical resection, or superficial transitional cell bladder carcinoma.
• Known active Hepatitis A, B or C.
• Known HIV seropositivity.
• Women who are pregnant or lactating.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• CTI BioPharma: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes

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; Azacitidine; Decitabine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Courtney DiNardo, MD/Assistant Professor
• Organization: The University of Texas MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

713-794-1141

Study Officials

• Courtney DiNardo, MD

  M.D. Anderson Cancer Center

  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: June 10, 2015
• First Posted: June 11, 2015
• Study Start: September 30, 2015
• Primary Completion: June 3, 2017
• Study Completion: June 3, 2017
• Last Updated: October 16, 2018
• Results First Posted: April 23, 2018

Record last verified: 2018-05

Locations

US (1)