Pacritinib Before Transplant for Myeloproliferative Neoplasms (MPN)

Phase 2

Terminated

• Conditions: Myeloproliferative Diseases
• Interventions: Drug: Pacritinib; Drug: Busulfan; Behavioral: Questionnaires; Behavioral: Phone Calls; Procedure: Allogeneic Stem Cell Transplantation; Drug: Fludarabine

• Registration Number: NCT02410551
• Lead Sponsor: M.D. Anderson Cancer Center

Brief Summary

The goal of this clinical research study is to learn if giving pacritinib before standard of care drugs followed by an allogeneic stem cell transplant can help to control myeloproliferative neoplasms. The safety of this therapy will also be studied.

Detailed Description

Study Drug Administration:

If you are found to be eligible to take part in this study, you will take pacritinib at about the same time each day by mouth, 2 times each day. Your doctor will tell you when to start and stop taking pacritinib. You may be able to take the drug for about 2-6 months depending on how you tolerate the drug and when your transplant date is. If you do not receive your transplant, you may be able to continue taking the study drug as long as the doctor thinks it is in your best interest.

You must swallow the capsules whole with a glass (about 8 ounces) of water. Do not open, break, or chew the capsules.

If you vomit or miss a dose of pacritinib, take your next dose of pacritinib at your regular time. Do not "make up" a missed or vomited dose.

You will be given a study drug diary to write down what time you take each dose of pacritinib. You need to bring the study drug diary, any leftover study drug, and any empty study drug containers with you to each study visit.

The dose of pacritinib you receive may be lowered or stopped, if the doctor thinks it is needed.

About 21 days after your last dose of pacritinib, you will given standard of care drugs and you will have an allogeneic stem cell transplant. Your doctor will explain this treatment and the stem cell transplant to you in more detail. You will be required to sign a separate consent form.

Study Visits:

One (1) time each month:

* You will have a physical exam.

* Blood (about 2 teaspoons) will be drawn for routine tests and to check your kidney and liver function.

* You will have an electrocardiogram (EKG -- a test that measures the electrical activity of the heart).

On Day 14 (+/- 2 days) of of Cycle 1, blood (about 2 teaspoons) will be drawn for routine tests and to check your kidney and liver function. You can have this blood drawn at a local lab or clinic that is closer to your home. The results will be sent to the study doctor at MD Anderson.

During Week 2 of Cycle 1, a member of the study staff will call to ask you about any symptoms you may be having. This call should last about 5-10 minutes.

Length of Study:

You will be on study for up to 1 year after the transplant. You may be taken off study early if the disease gets worse, if you have any intolerable side effects, of if you are unable to follow study directions.

Your participation on this study will be over after about 1 year of follow-up tests.

End-of-Study Visit:

Within about 7 days after your last dose of pacritinib, but before your stem cell transplant:

* You will have a physical exam and an ultrasound, MRI, or CT scan of your abdomen to measure your liver and spleen.

* You will have an EKG.

Before your transplant, you will have a bone marrow biopsy/aspiration to check the status of the disease.

Follow-Up Tests:

You will have follow-up visits at about 1, 3, 6, and 12 months after the transplant:

* You will complete 3 questionnaires about your symptoms and quality of life. It should take about 20-30 minutes to complete the questionnaires.

* At Month 3, you will have a physical exam and an ultrasound, MRI, or CT scan of your abdomen to measure your liver and spleen. This will be repeated at Month 12, if your doctor thinks it is needed.

* At Months 3 and 12, you will have a bone marrow biopsy/aspiration 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. The study doctor can explain how the study drug is designed to work.

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

Study Timeline

• Study First Submitted: 2015-04-02
• Study First Submitted QC: 2015-04-02
• Study First Posted: 2015-04-07
• Study Start: 2015-06-15
• Primary Completion: 2017-01-20
• Study Completion: 2017-01-20
• Results First Submitted: 2018-02-28
• Status Verified: 2018-10
• Results First Submitted QC: 2018-10-03
• Last Update Submitted: 2018-10-04
• Results First Posted: 2018-10-05
• Last Update Posted: 2018-10-30

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 4

Inclusion Criteria

1. Patients with Idiopathic Myelofibrosis or Myelofibrosis secondary to Polycythemia Vera or Essential Thrombocythemia.
2. Patients 18 years to less than or equal to 70 years.
3. Patients wanting to pursue transplant.
4. Patients must have a Zubrod PS equal or less than 2.
5. Calculated creatinine clearance greater than 50ml/min. using the Cockcroft-Gault equation.
6. Ejection fraction equal or above 40%.
7. Serum direct bilirubin less than 1 mg/dl (unless due to Gilbert's syndrome or hemolysis).
8. SGPT equal or less than 4 x normal values.
9. Corrected DLCO equal or above 50% of expected.
10. Negative Beta HCG test in a woman with childbearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization) and if fertile, males and females must agree to use contraceptives.

Exclusion Criteria

1. Patients with low risk myelofibrosis.
2. Uncontrolled life-threatening infections.
3. HIV positive.
4. Patients with active viral hepatitis.
5. Prior treatment with Pacritinib.
6. Prior stem cell transplant.
7. QTc greater than 450 ms.
8. CYP3A4 strong or moderate inhibitors/inducers in the past 7 days.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Pacritinib + Allogeneic Stem Cell Transplantation	Allogeneic Stem Cell Transplantation	Participants start Pacritinib 200 mg by mouth twice a day. Participants proceed to transplant after 60 days of Pacritinib but not more than 180 days. Pacritinib stopped 21 days prior to starting preparative regimen for standard of care stem cell transplantation (SOC Allo TP). SOC transplant conditioning with Fludarabine and Busulfan AUC of 4000 microMol-min per day providing that pharmacokinetic can be done, otherwise Busulfan dose given as a fixed dose of 100 mg/m2 daily for four days. Questionnaires about symptoms and quality of life completed at baseline, 1, 3, 6, and 12 months after transplant. Phone calls made by study staff to participant on second and third week of each month.
Pacritinib + Allogeneic Stem Cell Transplantation	Questionnaires	Participants start Pacritinib 200 mg by mouth twice a day. Participants proceed to transplant after 60 days of Pacritinib but not more than 180 days. Pacritinib stopped 21 days prior to starting preparative regimen for standard of care stem cell transplantation (SOC Allo TP). SOC transplant conditioning with Fludarabine and Busulfan AUC of 4000 microMol-min per day providing that pharmacokinetic can be done, otherwise Busulfan dose given as a fixed dose of 100 mg/m2 daily for four days. Questionnaires about symptoms and quality of life completed at baseline, 1, 3, 6, and 12 months after transplant. Phone calls made by study staff to participant on second and third week of each month.
Pacritinib + Allogeneic Stem Cell Transplantation	Phone Calls	Participants start Pacritinib 200 mg by mouth twice a day. Participants proceed to transplant after 60 days of Pacritinib but not more than 180 days. Pacritinib stopped 21 days prior to starting preparative regimen for standard of care stem cell transplantation (SOC Allo TP). SOC transplant conditioning with Fludarabine and Busulfan AUC of 4000 microMol-min per day providing that pharmacokinetic can be done, otherwise Busulfan dose given as a fixed dose of 100 mg/m2 daily for four days. Questionnaires about symptoms and quality of life completed at baseline, 1, 3, 6, and 12 months after transplant. Phone calls made by study staff to participant on second and third week of each month.
Pacritinib + Allogeneic Stem Cell Transplantation	Pacritinib	Participants start Pacritinib 200 mg by mouth twice a day. Participants proceed to transplant after 60 days of Pacritinib but not more than 180 days. Pacritinib stopped 21 days prior to starting preparative regimen for standard of care stem cell transplantation (SOC Allo TP). SOC transplant conditioning with Fludarabine and Busulfan AUC of 4000 microMol-min per day providing that pharmacokinetic can be done, otherwise Busulfan dose given as a fixed dose of 100 mg/m2 daily for four days. Questionnaires about symptoms and quality of life completed at baseline, 1, 3, 6, and 12 months after transplant. Phone calls made by study staff to participant on second and third week of each month.
Pacritinib + Allogeneic Stem Cell Transplantation	Busulfan	Participants start Pacritinib 200 mg by mouth twice a day. Participants proceed to transplant after 60 days of Pacritinib but not more than 180 days. Pacritinib stopped 21 days prior to starting preparative regimen for standard of care stem cell transplantation (SOC Allo TP). SOC transplant conditioning with Fludarabine and Busulfan AUC of 4000 microMol-min per day providing that pharmacokinetic can be done, otherwise Busulfan dose given as a fixed dose of 100 mg/m2 daily for four days. Questionnaires about symptoms and quality of life completed at baseline, 1, 3, 6, and 12 months after transplant. Phone calls made by study staff to participant on second and third week of each month.
Pacritinib + Allogeneic Stem Cell Transplantation	Fludarabine	Participants start Pacritinib 200 mg by mouth twice a day. Participants proceed to transplant after 60 days of Pacritinib but not more than 180 days. Pacritinib stopped 21 days prior to starting preparative regimen for standard of care stem cell transplantation (SOC Allo TP). SOC transplant conditioning with Fludarabine and Busulfan AUC of 4000 microMol-min per day providing that pharmacokinetic can be done, otherwise Busulfan dose given as a fixed dose of 100 mg/m2 daily for four days. Questionnaires about symptoms and quality of life completed at baseline, 1, 3, 6, and 12 months after transplant. Phone calls made by study staff to participant on second and third week of each month.

Primary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS)	participants who received Pacritinib for >/= 60 days but less than 180 days who undergo transplant with a matched related or at least 7/8 matched unrelated donor. The protocol was to evaluate progression free survival at one year.	The protocol was to enroll at least 21 evaluable participants, defined as patients who received Pacritinib for \>/=60 days but less than 180 days. We enrolled four participants, however all four were not evaluable since no one was able to complete 60 days of Pacritinib.

Trial Locations

Locations (1)

University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States