- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06414681
Combination of Tagraxofusp With Pacritinib in Patients With Intermediate-1 or Higher Myelofibrosis, Who Have Had Prior Therapy With the Approved JAK Inhibitors or in Which Therapy With the Approved JAK Inhibitors is Not Appropriate, Contraindicated or Declined
An Open Label Pilot Trial of the Combination of Tagraxofusp With Pacritinib in Patients With Intermediate-1 or Higher Myelofibrosis, Who Have Had Prior Therapy With the Approved JAK Inhibitors or in Which Therapy With the Approved JAK Inhibitors is Not Appropriate, Contraindicated or Declined
The goal of this open-label, single-center, pilot trial is to test the combination of Tagraxofusp (TAG) with Pacritinib (PAC) in patients with intermediate-II or higher myelofibrosis (MF), who have had prior therapy with the approved JAK1/2 inhibitor or in which therapy with the approved JAK1/2 inhibitors is not appropriate, contraindicated or declined by the subjects.
The Primary Objective is to:
1. Characterized efficacy of the combination of Tagraxofusp and Pacritinib.
The Secondary Objective is to:
1. characterize the safety profile of the combination Tagraxofusp and Pacritinib.
2, Characterize the feasibility of the combination Tagraxofusp and Pacritinib. 3. Characterize hematologic improvement with the combination Tagraxofusp and Pacritinib.
4. Evaluate and compare the effect of Tagraxofusp and Pacritinib on participant reports of MF symptoms.
Exploratory:
Pharmacokinetic (PK) testing of Tagraxofusp and Pacritinib to assess clinical predictors of response.
Next Generation Sequencing (NGS) Testing to define the number and the allele burden of pathological mutations, as well as the changes over the course of therapy, both in regard to progression and response.
Blood will be collected and stored at KU BRCF for future study related PK analysis
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Early Phase 1
Contacts and Locations
Study Contact
- Name: KUCC Navigation
- Phone Number: 913-588-3671
- Email: kucc_navigation@kumc.edu
Study Contact Backup
- Name: Jan Ward
- Phone Number: 913-588-1809
- Email: jward3@kumc.edu
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Ability of participant OR Legally Authorized Representative (LAR) to understand this study, and participant or LAR willingness to sign a written informed consent.
- The participant or LAR has signed informed consent prior to initiation of any study-specific procedures or treatment.
- The patient is able to adhere to the study visit schedule and other protocol requirements.
- Males and females age ≥ 18 years.
- ECOG Performance Status 0 - 2 (Appendix A).
- Life expectancy of > 6 months.
- Patient meets the 2016 WHO diagnostic criteria for MF and has an IPSS/DIPSS/DIPSS-plus intermediate-II or higher-risk disease.
- Patients who have indications for therapy per investigator or patient's choice, such as Splenomegaly, >5 CM BCM or mTSS ≥ 8 or mTSS Itching, night sweats, or bone pain ≥ 5 or Significant cytopenias including Hgb <10 g/dl, Platelet count less than 75 k/UL
Patients treated with a JAK inhibitor for >3 months and:
had inadequate response to treatment, i.e., < 10% reduction of spleen by imaging, or less than 25% reduction by spleen length on physical exam or lack of control of MF symptoms that is not satisfactory to the patient. NOTE: Participants who had contraindication to therapy with the approved JAK inhibitor including subject's refusal of therapy are eligible.
- A least 4 weeks have elapsed between the last dose of any MF-directed drug treatments, including hydroxyurea (HU), Interferon or glucocorticosteroids. NOTE: If patient is on a stable dose of glucocorticosteroids for another indication, they will be allowed into this study, AND patients on a stable dose of erythropoiesis-stimulating agents (ESA) are allowed on the study.
- Patient is not eligible for an immediate allo-SCT.
Adequate baseline organ, cardiac, and renal function as defined by:
LVEF ≥ 50% by ECHO within 6 months of study treatment initiation No clinically significant abnormalities on a 12-lead ECG, and no QTcF ≥ 480 msec Serum creatinine ≤ 1.5 mg/dL Serum albumin ≥ 3.2 g/dL (Note: albumin infusions are not permitted to enable eligibility) INR and PTT ≤ 1.5x ULN Albumin Supplementation Prior to the first dose, participant must have serum albumin ≥ to 3.2 g/dL.
Note- for any participants with serum albumin ≤ to 4.0 g/dL, it will be advisable but up to physician's discretion to administer 25g increments of albumin infusion before the first dose.
Total bilirubin ≤ 4x ULN AST and ALT ≤ 5 x ULN ANC ≥ 0.5 x 109/L PT or INR and PTT < = 1.5 x ULN
If the patient is a woman of child-bearing potential (WOCBP), they should have a negative serum pregnancy test no more than 7 days prior to start of treatment.
(Note: WOCBP include any female who has experienced menarche and who has not undergone successful sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea ≥ 12 consecutive months; or women on hormone replacement therapy with documented serum follicle stimulating hormone level ≥ 35 mIU/mL).
- Women of child-bearing potential and men with partners of child-bearing potential must agree to practice sexual abstinence or to use the forms of contraception listed in Child-Bearing Potential/Pregnancy section for the duration of study participation and for 3 months following completion of therapy.
Exclusion Criteria:
- Simultaneously enrolled in any therapeutic clinical trial
- Current or anticipating use of other anti-neoplastic or investigational agents while participating in this study.
- The patient has received treatment with chemotherapy, wide-field radiation, or biologic therapy within 14 days of study entry.
- The patient has received treatment with another investigational agent within 14 days of study entry.
- Diagnosed with a psychiatric illness or is in a social situation that would limit compliance with study requirements.
- Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, disseminated intravascular coagulation.
- Any condition or other contraindication to therapy as deemed by the principal investigator to place the subject at an unacceptably high risk for toxicities.
- Is pregnant or breastfeeding.
- Has a known allergic reaction to any excipient contained in the study drug formulation.
- Active Grade 3 (per the NCI CTCAE, Version 5.0) or higher viral, bacterial, or fungal infection within 2 weeks prior to the first dose of study treatment.
- Prior therapy with Tagraxofusp or Pacritinib.
- Presence of peripheral blood or bone marrow blast count > 10%
- Active Graft versus Host Disease (GVHD)
For patients who have previously had Stem Cell Therapy (SCT) - The patient is receiving immunosuppressive therapy.
EXCEPTION: low-dose prednisone (≤10 mg/day) - for treatment or prophylaxis of graft-versus-host disease (GVHD). If the patient has been on immunosuppressive treatment or prophylaxis for GVHD, the treatment(s) must have been discontinued at least 14 days prior to study treatment and there must be no evidence of Grade ≥ 2 GVHD.
- Other uncontrolled active malignancy as determined by the principal investigator
- The patient has an active malignancy and/or cancer history that may confound the assessment of the study endpoints. Patients with a past cancer history (within 2 years of entry) with substantial potential for recurrence and/or ongoing active malignancy must be discussed with the Sponsor before study entry. Patients with the following neoplastic diagnoses are eligible: non-melanoma skin cancer, carcinoma in situ, cervical intraepithelial neoplasia, organ-confined prostate cancer with no evidence of progressive disease.
- The patient has clinically significant cardiovascular disease (e.g. uncontrolled or any New York Heart Association Class 2 or greater congestive heart failure, uncontrolled angina, history of myocardial infarction, unstable angina or stroke within 6 months prior to study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication).
- Any gastrointestinal or metabolic condition that could interfere with absorption of oral medication.
- Prior therapy with Pacritinib (PAC) or Tagraxofusp (TAG).
- The patient has persistent clinically significant toxicities Grade ≥ 2 from previous therapies, including cytotoxic chemotherapy, targeted therapies, biological therapies, or immunotherapies, not readily controlled by supportive measures (excluding alopecia, nausea, and fatigue).
- The patient has uncontrolled, clinically significant pulmonary disease (e.g. chronic obstructive pulmonary disease, pulmonary hypertension) that in the opinion of the Investigator would put the patient at significant risk for pulmonary complications during the study.
- The patient has known active or suspected central nervous system (CNS) disease. If suspected, CNS disease should be ruled out with relevant imaging and/or examination of cerebrospinal fluid.
Current systemic treatment with strong or moderate CYP3A4 inhibitor or P450 inducer.
EXCEPTION: Patients who discontinue this treatment by Day 14 before start of treatment (Day -14) or 5 half-lives, whichever is shorter.
- Use of full-dose anticoagulation and use of anti-platelet therapy other than aspirin 81mg daily within 14 days prior to D1.
- Recent unprovoked bleeding of grade ≥ 2 within the last 3 months prior to Day 1.
- Active uncontrolled diarrhea or inflammatory bowel disease (IBD)
- Known sero-positivity for Hepatitis A (HAV), Hepatitis B (HBV), Hepatitis C (HCV), Human Immunodeficiency Virus (HIV)
- Patients with history of clinically significant bleeding or on anticoagulants
- Patients with moderate (Child-Pugh B ) and severe (Child -Pugh C) hepatic impairment will not be enrolled in the study.
- Patients with eGFR < 30 mL/min will not be enrolled
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Tagrxofusp (IV) in combination with Pacritinib (Oral)
Tagraxofusp Patients will receive 12 micrograms/kg of Tagraxofusp (TAG) by IV infusion once daily for 3 consecutive days. Pacritinib Pacritinib (PAC) will be given orally, 200 mg twice per day starting at C2D4 and administered continuously (Subsequent cycles start on Day 1 of the Cycle). |
Tagraxofusp Patients will receive 12 micrograms/kg of Tagraxofusp (TAG) by IV infusion once daily for 3 consecutive days.
Pacritinib Pacritinib (PAC) will be given orally, 200 mg twice per day starting at C2D4 and administered continuously (Subsequent cycles start on Day 1 of the Cycle).
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Spleen volume reduction by MRI or CT imaging, achieving ≥ 35% reduction in spleen volume imaging from baseline to week 24.
Time Frame: Baseline to up to 24 weeks
|
MRI of abdomen will be performed WITHOUT contrast.
If MRI is contraindicated - CT scan will be allowed (IV contrast will be used unless contraindicated).
The same type of Imaging used at screening must continue to be used throughout the study.
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Baseline to up to 24 weeks
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Change from baseline in the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score Version 2.0 (MPN-SAF TSS 2.0) to week 24.
Time Frame: Baseline to up to 24 weeks
|
Improvement in symptoms: >/= 50% reduction in Modified Total Symptom Score (mTSS) from baseline to week 24 as measured by the Myeloproliferative Neoplasms Symptom Assessment Form Total Symptom Score Version 2.0 (MPN-SAF TSS 2.0).
The MPN Symptom Assessment Form) includes the assessment of symptoms that are relevant to myelofibrosis.
MPN-SAF was simplified to a concise and abbreviated tool called the MPN-SAF Total Symptom Score (MPN-SAF TSS), that is used for the assessment of the 10 most relevant symptoms in subjects with MPN (fatigue, concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, and fever) in both clinical practice and clinical trial settings.
The symptom severity is rated by subjects on a scale of 1 to10 MPN-SAF-TSS: a total score will be calculated by the addition of every individual symptom score.
The change from baseline will be statically measured and reported.
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Baseline to up to 24 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of participants with Treatment-Related Adverse Events as Assessed by CTCAE v5.0 from baseline to End of Safety Follow-up (30 days after end of treatment).
Time Frame: Baseline to End of Safety follow up to End of Treatment (up to 1 year)
|
Number of participants with treatment related adverse events a assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
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Baseline to End of Safety follow up to End of Treatment (up to 1 year)
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Change from baseline in Anemia (hemoglobin GM/DL, iron ug/DL, and hematocrit %) improvement within or at 1 year
Time Frame: Baseline, Week 24 and End of Treatment (up to 1 year)
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From Baseline to best response within 1 year
|
Baseline, Week 24 and End of Treatment (up to 1 year)
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Patient's Global Impression (perception) of Change
Time Frame: Every cycle (each cycle is 28 days) day 1 starting at Cycle 2 to End of Treatment (up to 1 year)
|
Every cycle (each cycle is 28 days) day 1 starting at Cycle 2 to End of Treatment (up to 1 year)
|
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Improvement in Quality of Life based on Patient Impression of Global Change (PGIC). A PGIC score of 2 for "much improved" or a score of 1 for "very much improved."
Time Frame: Baseline to up to 24 weeks
|
Based on the proportion of patients who report "much improved" or "very much improved" symptoms at Week 24 based on the Patient Impression of Global Change (PGIC). A PGIC score of 2 for "much improved" or a score of 1 for "very much improved." The PGIC uses a score between 1 and 7 (1 being "very much improved" to 7 being "very much worse)." |
Baseline to up to 24 weeks
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Change from baseline in platelet count in K/UL within 1 year
Time Frame: Baseline, up to 24 weeks and End of Treatment (up to 1 year)
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From Baseline to best response within 1 year
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Baseline, up to 24 weeks and End of Treatment (up to 1 year)
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Change from baseline in Anemia (iron ug/DL)
Time Frame: Baseline, Week 24 and End of Treatment (up to 1 year)
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From Baseline to best response within 1 year
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Baseline, Week 24 and End of Treatment (up to 1 year)
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Change from baseline in Anemia (hematocrit %)
Time Frame: Baseline, Week 24 and End of Treatment (up to 1 year)
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From Baseline to best response within 1 year
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Baseline, Week 24 and End of Treatment (up to 1 year)
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Collaborators and Investigators
Investigators
- Principal Investigator: Abdulraheem Yacoub, Doctor of Medicine, The University of Kansas Medical Center
Publications and helpful links
General Publications
- Harrison C, Kiladjian JJ, Al-Ali HK, Gisslinger H, Waltzman R, Stalbovskaya V, McQuitty M, Hunter DS, Levy R, Knoops L, Cervantes F, Vannucchi AM, Barbui T, Barosi G. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med. 2012 Mar 1;366(9):787-98. doi: 10.1056/NEJMoa1110556.
- Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, Catalano JV, Deininger M, Miller C, Silver RT, Talpaz M, Winton EF, Harvey JH Jr, Arcasoy MO, Hexner E, Lyons RM, Paquette R, Raza A, Vaddi K, Erickson-Viitanen S, Koumenis IL, Sun W, Sandor V, Kantarjian HM. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012 Mar 1;366(9):799-807. doi: 10.1056/NEJMoa1110557.
- Hurst H, Bolton J. Assessing the clinical significance of change scores recorded on subjective outcome measures. J Manipulative Physiol Ther. 2004 Jan;27(1):26-35. doi: 10.1016/j.jmpt.2003.11.003.
- Mesa RA, Vannucchi AM, Mead A, Egyed M, Szoke A, Suvorov A, Jakucs J, Perkins A, Prasad R, Mayer J, Demeter J, Ganly P, Singer JW, Zhou H, Dean JP, Te Boekhorst PA, Nangalia J, Kiladjian JJ, Harrison CN. Pacritinib versus best available therapy for the treatment of myelofibrosis irrespective of baseline cytopenias (PERSIST-1): an international, randomised, phase 3 trial. Lancet Haematol. 2017 May;4(5):e225-e236. doi: 10.1016/S2352-3026(17)30027-3. Epub 2017 Mar 20.
- Mascarenhas J, Hoffman R, Talpaz M, Gerds AT, Stein B, Gupta V, Szoke A, Drummond M, Pristupa A, Granston T, Daly R, Al-Fayoumi S, Callahan JA, Singer JW, Gotlib J, Jamieson C, Harrison C, Mesa R, Verstovsek S. Pacritinib vs Best Available Therapy, Including Ruxolitinib, in Patients With Myelofibrosis: A Randomized Clinical Trial. JAMA Oncol. 2018 May 1;4(5):652-659. doi: 10.1001/jamaoncol.2017.5818.
- Barbui T, Tefferi A, Vannucchi AM, Passamonti F, Silver RT, Hoffman R, Verstovsek S, Mesa R, Kiladjian JJ, Hehlmann R, Reiter A, Cervantes F, Harrison C, Mc Mullin MF, Hasselbalch HC, Koschmieder S, Marchetti M, Bacigalupo A, Finazzi G, Kroeger N, Griesshammer M, Birgegard G, Barosi G. Philadelphia chromosome-negative classical myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet. Leukemia. 2018 May;32(5):1057-1069. doi: 10.1038/s41375-018-0077-1. Epub 2018 Feb 27.
- Tefferi A. Primary myelofibrosis: 2013 update on diagnosis, risk-stratification, and management. Am J Hematol. 2013 Feb;88(2):141-50. doi: 10.1002/ajh.23384. Erratum In: Am J Hematol. 2013 May;88(5):437-45.
- Aldinucci D, Olivo K, Lorenzon D, Poletto D, Gloghini A, Carbone A, Pinto A. The role of interleukin-3 in classical Hodgkin's disease. Leuk Lymphoma. 2005 Mar;46(3):303-11. doi: 10.1080/10428190400013712.
- Aldinucci D, Poletto D, Gloghini A, Nanni P, Degan M, Perin T, Ceolin P, Rossi FM, Gattei V, Carbone A, Pinto A. Expression of functional interleukin-3 receptors on Hodgkin and Reed-Sternberg cells. Am J Pathol. 2002 Feb;160(2):585-96. doi: 10.1016/S0002-9440(10)64878-X.
- Black JH, McCubrey JA, Willingham MC, Ramage J, Hogge DE, Frankel AE. Diphtheria toxin-interleukin-3 fusion protein (DT(388)IL3) prolongs disease-free survival of leukemic immunocompromised mice. Leukemia. 2003 Jan;17(1):155-9. doi: 10.1038/sj.leu.2402744.
- Florian S, Sonneck K, Hauswirth AW, Krauth MT, Schernthaner GH, Sperr WR, Valent P. Detection of molecular targets on the surface of CD34+/CD38-- stem cells in various myeloid malignancies. Leuk Lymphoma. 2006 Feb;47(2):207-22. doi: 10.1080/10428190500272507.
- Jordan CT, Guzman ML, Noble M. Cancer stem cells. N Engl J Med. 2006 Sep 21;355(12):1253-61. doi: 10.1056/NEJMra061808. No abstract available.
- Jordan CT, Upchurch D, Szilvassy SJ, Guzman ML, Howard DS, Pettigrew AL, Meyerrose T, Rossi R, Grimes B, Rizzieri DA, Luger SM, Phillips GL. The interleukin-3 receptor alpha chain is a unique marker for human acute myelogenous leukemia stem cells. Leukemia. 2000 Oct;14(10):1777-84. doi: 10.1038/sj.leu.2401903.
- Lhermitte L, de Labarthe A, Dupret C, Lapillonne H, Millien C, Landman-Parker J, Hermine O, Baruchel A, Sigaux F, Macintyre E, Asnafi V. Most immature T-ALLs express Ra-IL3 (CD123): possible target for DT-IL3 therapy. Leukemia. 2006 Oct;20(10):1908-10. doi: 10.1038/sj.leu.2404349. Epub 2006 Aug 10. No abstract available.
- Munoz L, Nomdedeu JF, Lopez O, Carnicer MJ, Bellido M, Aventin A, Brunet S, Sierra J. Interleukin-3 receptor alpha chain (CD123) is widely expressed in hematologic malignancies. Haematologica. 2001 Dec;86(12):1261-9.
- Ratts R, Trujillo C, Bharti A, vanderSpek J, Harrison R, Murphy JR. A conserved motif in transmembrane helix 1 of diphtheria toxin mediates catalytic domain delivery to the cytosol. Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15635-40. doi: 10.1073/pnas.0504937102. Epub 2005 Oct 17.
- Tehranchi R, Woll PS, Anderson K, Buza-Vidas N, Mizukami T, Mead AJ, Astrand-Grundstrom I, Strombeck B, Horvat A, Ferry H, Dhanda RS, Hast R, Ryden T, Vyas P, Gohring G, Schlegelberger B, Johansson B, Hellstrom-Lindberg E, List A, Nilsson L, Jacobsen SE. Persistent malignant stem cells in del(5q) myelodysplasia in remission. N Engl J Med. 2010 Sep 9;363(11):1025-37. doi: 10.1056/NEJMoa0912228.
- van Rhenen A, Feller N, Kelder A, Westra AH, Rombouts E, Zweegman S, van der Pol MA, Waisfisz Q, Ossenkoppele GJ, Schuurhuis GJ. High stem cell frequency in acute myeloid leukemia at diagnosis predicts high minimal residual disease and poor survival. Clin Cancer Res. 2005 Sep 15;11(18):6520-7. doi: 10.1158/1078-0432.CCR-05-0468.
- Vergez F, Green AS, Tamburini J, Sarry JE, Gaillard B, Cornillet-Lefebvre P, Pannetier M, Neyret A, Chapuis N, Ifrah N, Dreyfus F, Manenti S, Demur C, Delabesse E, Lacombe C, Mayeux P, Bouscary D, Recher C, Bardet V. High levels of CD34+CD38low/-CD123+ blasts are predictive of an adverse outcome in acute myeloid leukemia: a Groupe Ouest-Est des Leucemies Aigues et Maladies du Sang (GOELAMS) study. Haematologica. 2011 Dec;96(12):1792-8. doi: 10.3324/haematol.2011.047894. Epub 2011 Sep 20.
- Mesa RA, Gotlib J, Gupta V, Catalano JV, Deininger MW, Shields AL, Miller CB, Silver RT, Talpaz M, Winton EF, Harvey JH, Hare T, Erickson-Viitanen S, Sun W, Sandor V, Levy RS, Kantarjian HM, Verstovsek S. Effect of ruxolitinib therapy on myelofibrosis-related symptoms and other patient-reported outcomes in COMFORT-I: a randomized, double-blind, placebo-controlled trial. J Clin Oncol. 2013 Apr 1;31(10):1285-92. doi: 10.1200/JCO.2012.44.4489. Epub 2013 Feb 19.
- Tefferi A. Challenges facing JAK inhibitor therapy for myeloproliferative neoplasms. N Engl J Med. 2012 Mar 1;366(9):844-6. doi: 10.1056/NEJMe1115119. No abstract available.
- Barosi G, Tefferi A, Besses C, Birgegard G, Cervantes F, Finazzi G, Gisslinger H, Griesshammer M, Harrison C, Hehlmann R, Hermouet S, Kiladjian JJ, Kroger N, Mesa R, Mc Mullin MF, Pardanani A, Passamonti F, Samuelsson J, Vannucchi AM, Reiter A, Silver RT, Verstovsek S, Tognoni G, Barbui T. Clinical end points for drug treatment trials in BCR-ABL1-negative classic myeloproliferative neoplasms: consensus statements from European LeukemiaNET (ELN) and Internation Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT). Leukemia. 2015 Jan;29(1):20-6. doi: 10.1038/leu.2014.250. Epub 2014 Aug 25.
- Harrison CN, Mesa RA, Kiladjian JJ, Al-Ali HK, Gisslinger H, Knoops L, Squier M, Sirulnik A, Mendelson E, Zhou X, Copley-Merriman C, Hunter DS, Levy RS, Cervantes F, Passamonti F, Barbui T, Barosi G, Vannucchi AM. Health-related quality of life and symptoms in patients with myelofibrosis treated with ruxolitinib versus best available therapy. Br J Haematol. 2013 Jul;162(2):229-39. doi: 10.1111/bjh.12375. Epub 2013 May 14.
- Mughal TI, Cross NC, Padron E, Tiu RV, Savona M, Malcovati L, Tibes R, Komrokji RS, Kiladjian JJ, Garcia-Manero G, Orazi A, Mesa R, Maciejewski JP, Fenaux P, Itzykson R, Mufti G, Solary E, List AF. An International MDS/MPN Working Group's perspective and recommendations on molecular pathogenesis, diagnosis and clinical characterization of myelodysplastic/myeloproliferative neoplasms. Haematologica. 2015 Sep;100(9):1117-30. doi: 10.3324/haematol.2014.114660.
- Prager BC, Xie Q, Bao S, Rich JN. Cancer Stem Cells: The Architects of the Tumor Ecosystem. Cell Stem Cell. 2019 Jan 3;24(1):41-53. doi: 10.1016/j.stem.2018.12.009.
- Desai A, Yan Y, Gerson SL. Concise Reviews: Cancer Stem Cell Targeted Therapies: Toward Clinical Success. Stem Cells Transl Med. 2019 Jan;8(1):75-81. doi: 10.1002/sctm.18-0123. Epub 2018 Oct 17.
- Yan B, Chen Q, Shimada K, Tang M, Li H, Gurumurthy A, Khoury JD, Xu B, Huang S, Qiu Y. Histone deacetylase inhibitor targets CD123/CD47-positive cells and reverse chemoresistance phenotype in acute myeloid leukemia. Leukemia. 2019 Apr;33(4):931-944. doi: 10.1038/s41375-018-0279-6. Epub 2018 Oct 5.
- Arai N, Homma M, Abe M, Baba Y, Murai S, Watanuki M, Kawaguchi Y, Fujiwara S, Kabasawa N, Tsukamoto H, Uto Y, Ariizumi H, Yanagisawa K, Hattori N, Saito B, Shiozawa E, Harada H, Yamochi-Onizuka T, Nakamaki T, Takimoto M. Impact of CD123 expression, analyzed by immunohistochemistry, on clinical outcomes in patients with acute myeloid leukemia. Int J Hematol. 2019 May;109(5):539-544. doi: 10.1007/s12185-019-02616-y. Epub 2019 Mar 7.
- Stevens BM, Zhang W, Pollyea DA, Winters A, Gutman J, Smith C, Budde E, Forman SJ, Jordan CT, Purev E. CD123 CAR T cells for the treatment of myelodysplastic syndrome. Exp Hematol. 2019 Jun;74:52-63.e3. doi: 10.1016/j.exphem.2019.05.002. Epub 2019 May 25.
- Frolova O, Frankel AE, Korchin B, et al. IL3R-Directed Agents, SL-401 and SL-501, Inhibit the Growth of Leukemia Stem cells in CML. Blood (ASH Meeting Abstracts) 2010 116: Abstract 3403
- Lucas N, Duchmann M, Rameau P, Noel F, Michea P, Saada V, Kosmider O, Pierron G, Fernandez-Zapico ME, Howard MT, King RL, Niyongere S, Diop MK, Fenaux P, Itzykson R, Willekens C, Ribrag V, Fontenay M, Padron E, Soumelis V, Droin N, Patnaik MM, Solary E. Biology and prognostic impact of clonal plasmacytoid dendritic cells in chronic myelomonocytic leukemia. Leukemia. 2019 Oct;33(10):2466-2480. doi: 10.1038/s41375-019-0447-3. Epub 2019 Mar 20.
- Rapoport AP, Luhowskyj S, Doshi P, DiPersio JF. Mutational analysis of the alpha subunit of the human interleukin-3 receptor. Blood. 1996 Jan 1;87(1):112-22.
- Kochi SK, Collier RJ. DNA fragmentation and cytolysis in U937 cells treated with diphtheria toxin or other inhibitors of protein synthesis. Exp Cell Res. 1993 Sep;208(1):296-302. doi: 10.1006/excr.1993.1249.
- Pemmaraju N, Lane AA, Sweet KL, Stein AS, Vasu S, Blum W, Rizzieri DA, Wang ES, Duvic M, Sloan JM, Spence S, Shemesh S, Brooks CL, Balser J, Bergstein I, Lancet JE, Kantarjian HM, Konopleva M. Tagraxofusp in Blastic Plasmacytoid Dendritic-Cell Neoplasm. N Engl J Med. 2019 Apr 25;380(17):1628-1637. doi: 10.1056/NEJMoa1815105.
- Stemline Therapeutics, Inc. ELZONRIS (Tagraxofusp-erzs) Investigator's Brochure Version 6.0 dated 04-20-2021
- CTI Biopharma Corp. Pacritinib (SB1518) Investigator Brochure (IND 78,4806) Version 13 dated 02-27-2020
- Stemline Therapeutics. Tagraxofusp Protocol Guidance for the Investigator. Version 2.0 dated 09-29-2021. Provided by Stemline Therapeutics
- CTI Biopharma Corp. VONJO (Pacritinib) Package Insert dated 02-2022
- Stemline Therapeutics, Inc. Protocol Number STML-401-0314 Amendment 8 dated 05-05-2020. Tagraxofusp (SL-401) in Patients with Chronic Myelomonocytic Leukemia (CMML) or Myelofibrosis (MF)
Helpful Links
- The Impact of Pacritinib on Myelofibrosis Symptoms in Patients with Moderate and Severe Thrombocytopenia: A Retrospective Analysis of Patients in the Persist-2 Study. Blood (2021) 138 (Supplement 1): 3628.
- U.S Food and Drug Administration - News and Events for Human Drugs. FDA approves drug for adults with rare form of bone marrow disorder
- Pacritinib Granted Accelerated Approval for Use in Myelofibrosis With Severe Thrombocytopenia
- Indiana University School of Medicine, Department of Medicine, Clinical Pharmacology. Drug Interaction Flockhart Table
- U.S. Food & Drug Administration. For Healthcare Professionals | FDA's Examples of Drugs that Interact with CYP Enzymes and Transporter Systems
- Results of the Persist-2 Phase 3 Study of Pacritinib (PAC) Versus Best Available Therapy (BAT), Including Ruxolitinib (RUX), in Patients (pts) with Myelofibrosis (MF) and Platelet Counts <100,000/µl. Blood. Volum
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- STUDY00160238
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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Clinical Trials on Myelofibrosis,MF
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AbbVieActive, not recruitingMyelofibrosis (MF)United States, Australia, Belgium, Bulgaria, Canada, Croatia, France, Greece, Hungary, Israel, Italy, Japan, Korea, Republic of, Poland, Puerto Rico, Russian Federation, Serbia, Spain, Taiwan, Turkey, United Kingdom
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AbbVieActive, not recruitingMyelofibrosis (MF)United States, Australia, Austria, Belgium, Bulgaria, Canada, Croatia, Czechia, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Japan, Korea, Republic of, New Zealand, Poland, Puerto Rico, Russian Federation, Serbia, South... and more
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AbbVieActive, not recruitingMyelofibrosis (MF)United States, Australia, Austria, Belgium, Bulgaria, Canada, Croatia, France, Germany, Greece, Israel, Italy, Japan, Korea, Republic of, Netherlands, New Zealand, Russian Federation, Serbia, South Africa, Spain, Sweden, Taiwan, Turkey and more
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AbbVieActive, not recruitingMyelofibrosis (MF)United States, Argentina, Australia, Brazil, Bulgaria, Chile, Hungary, Israel, Italy, Japan, Korea, Republic of, Spain, Sweden, Turkey
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AbbVieTerminatedMyelofibrosis (MF)United States, Korea, Republic of, South Africa
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Telios Pharma, Inc.RecruitingPrimary Myelofibrosis | Myelofibrosis | Post-PV MF | Post-ET MyelofibrosisSpain, United States, France, Poland, Italy, Germany
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Kartos Therapeutics, Inc.Telios Pharma, Inc.RecruitingPrimary Myelofibrosis | Myelofibrosis | Post-PV MF | Post-ET MyelofibrosisUnited States, Italy, Serbia, Poland, France, Austria, Bulgaria, Germany, Hungary, Spain
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University of UlmActive, not recruitingPrimary Myelofibrosis | Secondary Myelofibrosis | Post-PV MF | PMF | SMF | Post-ET MFGermany
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Marina KremyanskayaIncyte CorporationWithdrawnMyelofibrosis | MF
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Suzhou Zelgen Biopharmaceuticals Co.,LtdCompletedPrimary Myelofibrosis (PMF) | Post-polycythemia Vera Myelofibrosis(Post-PV MF) | Post-essential Thrombocythemia Myelofibrosis(Post-ET MF)China
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Gruppo Italiano Malattie EMatologiche dell'AdultoRecruitingAcute Myeloid LeukemiaItaly
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Stemline Therapeutics, Inc.CompletedMyelofibrosis | Chronic Myelomonocytic LeukemiaUnited States, Canada
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Stemline Therapeutics, Inc.TerminatedAcute Myeloid LeukemiaUnited States
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Karen Ballen, MDRecruitingAcute Myeloid Leukemia | Myelofibrosis | Chronic Myelomonocytic LeukemiaUnited States
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M.D. Anderson Cancer CenterNational Cancer Institute (NCI)CompletedBlastic Plasmacytoid Dendritic Cell NeoplasmUnited States
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Joshua ZeidnerUniversity of North Carolina, Chapel Hill; Stemline Therapeutics, Inc.RecruitingAcute Myeloid LeukemiaUnited States
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Sidney Kimmel Comprehensive Cancer Center at Johns...StemlineTherapeutics, Inc.RecruitingAcute Myeloid LeukemiaUnited States
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M.D. Anderson Cancer CenterRecruitingChronic Myelomonocytic Leukemia | Myelodysplastic/Myeloproliferative Neoplasm | Chronic Myelomonocytic Leukemia-1 | Chronic Myelomonocytic Leukemia-2United States
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Jonsson Comprehensive Cancer CenterStemline Therapeutics, Inc.WithdrawnAcute Myeloid LeukemiaUnited States
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Stemline Therapeutics, Inc.TerminatedMultiple MyelomaUnited States