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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT02469415

Recruitment Status : Terminated (FDA Clinical Hold)

First Posted : June 11, 2015

Results First Posted : April 23, 2018

Last Update Posted : October 16, 2018

Sponsor:

Collaborator:

CTI BioPharma

Information provided by (Responsible Party):

M.D. Anderson Cancer Center

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Leukemia	Drug: Pacritinib Drug: 5-azacitidine Drug: Decitabine	Phase 2

Show detailed description

Detailed Description:

Study Drug Administration:

Each cycle is 28 days.

If you are found to be eligible to take part in this study, you will take pacritinib by mouth 2 times each day during Cycles 1-4. Each dose should be about 12 hours apart (1 dose in the morning, 1 dose in the evening).

After Cycle 4, if the study doctor thinks it is in your best interest, you may be able to continue taking pacritinib in combination with either azacitidine or decitabine. The study doctor will tell you which drug you will receive. The study doctor will tell you which drug you will receive. Decitabine and azacitidine may be administered by local doctor or at MD Anderson. Cycle 1 of Part 2 will be administered at MD Anderson. Commercial supplies of decitabine and azacitidine will be used.

You will receive either azacitidine by vein over about 1 hour on Days 1-5 of Cycles 5 and beyond or decitabine by vein over about 1 hour or as an injection under the skin on Days 1-7 of Cycles 5 and beyond.

You should return any unused study drug and/or any empty bottles to each study visit.

Study Visits:

One (1) time each week during Cycle 1 and then on Day 1 of each cycle after that, blood (about 1½ teaspoons) will be drawn for routine tests. You may have this blood drawn at a local lab or clinic closer to your home, if the study doctor thinks this is acceptable. The results from the blood draw will be sent to the study doctor.

On Day 28 (+/- 5 days) of Cycles 1 and 4, you will have a bone marrow aspiration/biopsy to check for genetic mutations and cytogenetic testing. If you begin receiving pacritinib in combination with either azacitidine or decitabine, you will also have this test repeated at Cycle 4 of your combination therapy.

On Day 1 of Cycle 1, Day 28 of Cycles 1 and 4, and at any time the doctor thinks it is needed, you will have an EKG.

Length of Treatment:

You may continue taking pacritinib for up to 4 cycles. If the doctor thinks it is in your best interest, you may be eligible to continue taking the study drug in combination with either azacitidine or decitabine for as long as the doctor thinks it is in your best interest.

You will no longer be able to take the study drug(s) if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Your participation on the study will be over after the end-of-treatment visit.

After the end of therapy and/or 30 days after your last dose of study drug, the study staff will follow your health status by phone call every 2 months (+/- 2 months) until you receive another cancer treatment.

End-of-Treatment Visit:

About 28 days after the last dose of study drug(s):

Blood (about 1½ teaspoons) will be drawn for routine tests.
If the doctor thinks it is needed, you will have a bone marrow aspirate/biopsy to check the status of the disease.

This is an investigational study. Pacritinib is not FDA approved or commercially available. It is currently being used for research purposes only. Azacitidine and decitabine are both FDA approved and commercially available for the treatment of MDS. The study doctor can explain how the study drugs are designed to work.

Up to 40 participants will take part in this study. All will be enrolled at MD Anderson.

Study Design

Layout table for study information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	3 participants
Allocation:	N/A
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Phase II Study of Pacritinib for Patients With Lower-Risk Myelodysplastic Syndromes
Actual Study Start Date :	September 30, 2015
Actual Primary Completion Date :	June 3, 2017
Actual Study Completion Date :	June 3, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Myelodysplastic Syndromes

Drug Information available for: Azacitidine Decitabine

Genetic and Rare Diseases Information Center resources: Myelodysplastic Syndromes

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Pacritinib + Azacitidine or Decitabine 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 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. Drug: 5-azacitidine Part 2 Starting Dose of 5-azacitidine: 75 mg/m2 by vein on Days 1 - 5 of Cycles 5 and beyond. Other Names: Azacitidine 5-azacytidine 5-aza Vidaza 5-AZC AZA-CR Ladakamycin NSC-102816 Azacytidine Drug: Decitabine Part 2 Starting Dose of Decitabine: 20 mg/m2 by vein on on Days 1 - 7 of Cycles 5 and beyond. Other Name: Dacogen

Arm

Intervention/treatment

Experimental: Pacritinib + Azacitidine or Decitabine

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

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.

Drug: 5-azacitidine

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

Other Names:

Azacitidine
5-azacytidine
5-aza
Vidaza
5-AZC
AZA-CR
Ladakamycin
NSC-102816
Azacytidine

Drug: Decitabine

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

Other Name: Dacogen

Outcome Measures

Primary Outcome Measures :

Overall Response Rate (ORR) [ Time Frame: 28 days ]
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.

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information

Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02469415

Locations

Layout table for location information

United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030

Sponsors and Collaborators

M.D. Anderson Cancer Center

CTI BioPharma

Investigators

Layout table for investigator information

Principal Investigator:	Courtney DiNardo, MD	M.D. Anderson Cancer Center

Study Documents (Full-Text)

Documents provided by M.D. Anderson Cancer Center:

Study Protocol and Statistical Analysis Plan [PDF] July 20, 2015

More Information

Additional Information:

University of Texas MD Anderson Cancer Center Website This link exits the ClinicalTrials.gov site

Layout table for additonal information

Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT02469415
Other Study ID Numbers:	2013-0224 NCI-2015-01306 ( Registry Identifier: NCI CTRP )
First Posted:	June 11, 2015 Key Record Dates
Results First Posted:	April 23, 2018
Last Update Posted:	October 16, 2018
Last Verified:	May 2018

Layout table for additional information

Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by M.D. Anderson Cancer Center:


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

Additional relevant MeSH terms:

Layout table for MeSH terms

Preleukemia Myelodysplastic Syndromes Neoplasms Bone Marrow Diseases Hematologic Diseases Precancerous Conditions Azacitidine	Decitabine Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Enzyme Inhibitors

To Top