Myeloproliferative Diseases
Conditions
Keywords
Myeloproliferative Diseases, Myeloproliferative Neoplasms, MPN, Myelofibrosis, Polycythemia vera, PV, Essential thrombocythemia, Allogeneic stem cell transplantation, Allo TP, Pacritinib, Busulfan, Busulfex, Myleran, Questionnaires, Surveys, Phone calls
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.
Interventions
DRUGPacritinib
200 mg by mouth twice a day for 60 days.
DRUGBusulfan
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.
BEHAVIORALQuestionnaires
Questionnaires completed at baseline, 1, 3, 6, and 12 months after transplant.
BEHAVIORALPhone Calls
Phone calls made by study staff to participant on second and third week of each month.
PROCEDUREAllogeneic Stem Cell Transplantation
Allogeneic stem cell transplantation (Allo TP) 60 days after starting Pacritinib but not more than 180 days.
DRUGFludarabine
Fludarabine taken along with Busulfan as per standard of care as preparative regimen for allogeneic stem cell transplantation (Allo TP).
Sponsors
CTI BioPharma
M.D. Anderson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Evaluate Safety and Efficacy of Pacritinib. | Start of Pacritinib to one year post transplant | Evaluate safety and efficacy of this therapy determined by Neutrophil and platelet engraftment, Non-relapse mortality at one year post transplant, Overall survival at one year post transplant, Liver and spleen response to Pacritinib, Immune recovery, quality of life and symptom score, Primary and secondary graft failure,Complete remission, Relapse. |
Countries
United States
Participant flow
Recruitment details
Patients with Idiopathic Myelofibrosis or Myelofibrosis secondary to Ploycythemia Vera or Essential Thrombocythemia that are 18 to 70 years old that want to pursue a transplant. They start the Pacritinib per-transplant and can proceed to transplant 60 days after starting Pacritinib but no more than 180 days.
Participants by arm
| Arm | Count |
|---|---|
| Pacritinib Pre- Transplant Patients will start pacritinib 200 mg po bid and can proceed to transplant after 60 days of starting pacritinib but not more than | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | FDA Clinical hold-patients taken off | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Pacritinib Pre- Transplant |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Region of Enrollment United States | 4 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 4 |
| other Total, other adverse events | 1 / 4 |
| serious Total, serious adverse events | 0 / 4 |
Outcome results
Primary
Progression-free Survival (PFS)
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.
Time frame: 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.
Population: Four participants were not evaluable and no analysis was done.
Other Pre-specified
Evaluate Safety and Efficacy of Pacritinib.
Evaluate safety and efficacy of this therapy determined by Neutrophil and platelet engraftment, Non-relapse mortality at one year post transplant, Overall survival at one year post transplant, Liver and spleen response to Pacritinib, Immune recovery, quality of life and symptom score, Primary and secondary graft failure,Complete remission, Relapse.
Time frame: Start of Pacritinib to one year post transplant
Population: Four participants was invaluable and no analysis was done.