Pacritinib in Combination With Low Dose Decitabine in Intermediate-High Risk Myelofibrosis or Myeloproliferative Neoplasm (MPN)/Myelodysplastic Syndrome (MDS)
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|ClinicalTrials.gov Identifier: NCT02564536|
Recruitment Status : Withdrawn (Lack of funding following full FDA clinical hold)
First Posted : September 30, 2015
Last Update Posted : May 8, 2017
For the first 28 day cycle, all patients will be treated with single agent pacritinib at 200 mg twice daily. The investigators chose this starting dose based on the previous three phase I studies of pacritinib as a single agent which showed that the maximum tolerated dose (MTD) to be 500 mg, and subsequently, the dose of 400 mg daily was recommended for the phase II studies.
Recently, the results of the phase III PERSIST-1 trial comparing pacritinib to best available therapy (BAT) in patients with MF was reported at the 2015 American Society of Clinical Oncology (ASCO) annual meeting. Pacritinib was found to be significantly more effective than BAT at reducing spleen volume at 24 weeks of therapy and improving constitutional symptoms.
Low dose decitabine has demonstrated depletion of DNMT1 in normal hematopoietic stem cells (HSC) without cytotoxicity and subcutaneous (SC) instead of intravenous (IV) administration may avoid high peak levels that can cause apoptosis. Furthermore, the low toxicity associated with low dose decitabine would allow for more frequent (1 to 3 times weekly) administration of the drug which would catch more cells in S-phase via greater exposure time. Based on these findings, a starting dose of decitabine 5 mg/m2 SC twice weekly should be well tolerated and effective in patients with MF and MPN/MDS syndromes when combined with pacritinib 400 mg daily.
|Condition or disease||Intervention/treatment||Phase|
|Chronic Myelomonocytic Leukemia Juvenile Myelomonocytic Leukemia Atypical Chronic Myeloid Leukemia Myeloproliferative Neoplasm Myelodysplastic Syndromes Myelofibrosis||Drug: Pacritinib Drug: Decitabine||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Study of Pacritinib in Combination With Low Dose Decitabine in Patients With Intermediate-High Risk Myelofibrosis or MPN/MDS Syndromes|
|Estimated Study Start Date :||June 2017|
|Estimated Primary Completion Date :||June 30, 2020|
|Estimated Study Completion Date :||June 30, 2020|
Experimental: Arm 1: Pacritinib and Decitabine
-Patients should take pacritinib at approximately the same times every day with a glass of water, with or without food.
-From commercial stock
- Safety of regimen as measured by adverse events [ Time Frame: 30 days after completion of treatment (up to 1 year) ]The descriptions and grading for adverse events are found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
- Rate of objective response as defined by the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) consensus [ Time Frame: End of treatment (up to 48 weeks) ]Objective response is defined as CR (complete remission/response) + PR (partial remission/response) + CI (clinical improvement).
- Rate of hematologic response [ Time Frame: End of treatment (up to 48 weeks) ]
Anemia response is only applicable for patients with baseline hemoglobin level less than 10g/dL for 8 weeks or more and requires:
*≥2 g/dL increase in hemoglobin level
*becoming transfusion-independent (no RBC transfusions in past 1 month)
Platelet response is only applicable for patients with a baseline platelet count of less than 50 x 10^9/L for 8 weeks or more, and requires:
- 100% increase in platelet count AND
- An absolute platelet count of at least 50 x 10^9/L
- Rate of symptom response as measured by the total symptom score (TSS) [ Time Frame: End of treatment (up to 48 weeks) ]A ≥50% reduction in the myeloproliferative neoplasm symptom assessment total symptom score
- Rate of spleen response [ Time Frame: End of treatment (up to 48 weeks) ]
- A baseline splenomegaly that is palpable at 5-10 cm below the left costal margin becomes not palpable OR
- A baseline splenomegaly that is palpable > 10 cm below the left costal margin decreases by ≥50% OR
- A baseline splenomegaly that is palpable < 5 cm below the left costal margin is not eligible for spleen response OR
- MRI or CT shows ≥35% spleen volume reduction
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): NCT02564536
|Principal Investigator:||Camille Abboud, M.D.||Washington University School of Medicine|