Blood and Lymph Conditions

All Conditions

Neoplasms

Symptoms and General Pathology

Heart and Blood Diseases

Rare Diseases

Thrombocytopenia

Anemia

Myeloproliferative Disorders

Polycythemia Vera

Polycythemia

Primary Myelofibrosis

Bone Marrow Diseases

Thrombocytosis

Thrombocythemia, Essential

Hematologic Diseases

Splenomegaly

Hemorrhagic Disorders

Blood Platelet Disorders

Cytopenia

Bone Marrow Neoplasms

Hematologic Neoplasms

Hemostatic Disorders

Blood Coagulation Disorders

Chronic Myeloproliferative Disorders

Essential Thrombocythemia

BAT includes any physician-selected treatment for myelofibrosis, such as approved JAK2 inhibitors administered according to package insert for patients with thrombocytopenia, and may include any treatment received before study entry.

Pacritinib

Best Available Therapy

Simran Singh

Phase 3, randomized, controlled study to evaluate the safety and efficacy of oral pacritinib compared to Best Available Therapy (BAT) in patients with thrombocytopenia and primary or secondary myelofibrosis.

Multicenter, randomized, controlled, phase 3 trial comparing the safety and efficacy of pacritinib with that of BAT in patients with thrombocytopenia and primary or secondary myelofibrosis. Approximately 300 eligible patients will be randomized in a 1:1:1 allocation to pacritinib 400 mg dosed QD, pacritinib 200 mg dosed BID, or BAT (includes any physician-selected treatment for myelofibrosis, such as approved JAK2 inhibitors administered according to package insert for patients with thrombocytopenia, and may include any treatment received before study entry). Spleen volume will be measured by MRI or CT at baseline and every 12 weeks thereafter. An independent radiology facility (IRF), blind to treatment assignments, will measure spleen volumes. Patients will also be followed for safety, Leukemia Free Survival (LFS), Overall Survival (OS), frequency of red blood cell (RBC) and platelet transfusions, and other exploratory endpoints. An Independent Data Monitoring Committee (IDMC) will evaluate the safety of pacritinib.

Pacritinib Versus Best Available Therapy to Treat Patients With Myelofibrosis and Thrombocytopenia

A Randomized Controlled Phase 3 Study of Oral Pacritinib Versus Best Available Therapy in Patients With Thrombocytopenia and Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis

Proportion of patients achieving a ≥ 35% reduction in spleen volume from baseline to week 24 as measured by magnetic resonance imaging (MRI) or computed tomography (CT).

Proportion of patients achieving a ≥ 50% reduction in the total symptom score from baseline to Week 24 on the Myeloproliferative Neoplasm Symptom Assessment Form 2.0 (MPN-SAF TSS 2.0). Responses (on a scale from 0 \[absent\] to 10 \[worst imaginable\]) to questions about symptoms (tiredness, early satiety, abdominal discomfort, night sweats, pruritus, bone pain, and pain under the ribs on the left side) were used to calculate the TSS.

CTI BioPharma

All-Cause Mortality was assessed in the Total Randomized Population (n=311). Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed in the Safety Population (n=308).

Pacritinib, Once Daily

Pacritinib, Twice Daily

BAT includes any physician-selected treatment for myelofibrosis, such as approved JAK2 inhibitors administered according to package insert for patients with thrombocytopenia, and may include any treatment received before study entry

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

New Zealand

Canada

Netherlands

Belgium

Hungary

United States

Czechia

United Kingdom

Australia

France

Germany

Russia

Region of Enrollment

Represents Intent To Treat population (number of randomized patients)

Beth Ziemba

BAT arm compared to pooled pacritinib arms (QD + BID - ITT Efficacy)

Spleen Volume Reduction

Total Symptom Score (TSS) Reduction

Pacritinib, QD

Pacritinib, BID

Overall Study

Leukemia

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Neoplasms by Histologic Type

Chronic Disease

Disease Attributes

Myeloid Leukemia

Chronic Graft Versus Host Disease

Chronic Myeloid Leukemia

All Drugs and Chemicals

Amino Acids

Asciminib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Patients will receive asciminib (40 mg BID continuous)

Patients will receive best available therapy chosen by investigator

Asciminib comes in 20 mg and 40 mg tablets and is taken orally twice daily

asciminib

Best available treatment will be based on investigator's choice identified prior to randomization. Dose and frequency will depend on label and institutional guidelines for various BAT

best available treatment

Novartis Pharmaceuticals

The purpose of this Chinese bridging study is to evaluate the efficacy, safety, tolerability and pharmacokinetics of asciminib versus best available therapy in Chinese patients with Chronic Myelogenous Leukemia in chronic phase, previously treated with 2 or more tyrosine kinase inhibitors to support related indication registration in China.

The primary objective of the study is to evaluate the Major Molecular Response (MMR) rate of asciminib treatment at 24 weeks.

The purpose of this Chinese bridging study is to evaluate the efficacy, safety, tolerability and pharmacokinetics (PK) of asciminib versus best available therapy (BAT) in Chinese patients with Chronic Myelogenous Leukemia in chronic phase (CML-CP), previously treated with 2 or more tyrosine kinase inhibitors (TKIs) to support related indication registration in China.

This study will enroll the participants 1) who failed their most recent TKI therapy by meeting the definition of treatment failure as per the 2013 European Leukemia Net (ELN) guidelines, or 2) who were intolerant to the most recent TKI therapy and must have BCR-ABL1 ratio \> 0.1% IS at screening.

Eligible participants will be randomized into asciminib arm or the BAT arm on a 2:1 ratio, to receive asciminib treatment (continuous 40 mg BID) or BAT from Day 1 until the end of study treatment period defined as 96 weeks after the last participant receives the first dose.

Study of Efficacy and Safety of CML-CP Patients Treated With Asciminib Versus Best Available Therapy, Previously Treated With 2 or More Tyrosine Kinase Inhibitors

A Randomized, Open-label, Multi-center, Phase II Study of Asciminib Versus Best Available Therapy in Chinese Patients With Chronic Myelogenous Leukemia in Chronic Phase (CML-CP), Previously Treated With 2 or More Tyrosine Kinase Inhibitors

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Evaluate the major molecular response rate at 24 weeks in asciminib arm

Evaluate the cytogenetic response rate (Complete, Partial, Major, Minor, Minimal, no response) at and by all scheduled data collection time points including 24, 48 and 96 weeks for both asciminib arm and best available treatment arm.

Evaluate the major molecular response rate at week 24 of best available treatment arm, and compare with asciminib arm

Evaluate the major molecular response rate, collected at all scheduled data collection time point (except week 24)

Evaluate the major molecular rate by all scheduled data collection time points including 24, 48 and 96 weeks by treatment group

Evaluate the time from the date of the first dose of study drug to the date of the first documented MMR by treatment group

First document major molecular response to loss of MMR up to 96 weeks after last participant receive the first dose

To evaluate the time from the date of randomization to the date of death (including the survival follow-up period)

Evaluate the time from the date of randomization to the earliest occurrence of documented disease progression to AP/BC or the date of death from any cause (including progressions and deaths observed during the survival follow-up period)

Characterize PK of asciminib in the Chinese CML-CP population. Cmax is the maximum (peak) observed plasma drug concentration after dose administration (ng/mL).

Characterize PK of asciminib in the Chinese CML-CP population. Tmax is the time to reach maximum (peak) plasma drug concentration after dose administration (hr).

Characterize PK of asciminib in the Chinese CML-CP population. Trough plasma concentrations (Ctrough)

Characterize PK of asciminib in the Chinese CML-CP population. The partial area under the plasma concentration-time curve from dose time to tau (ng\*hr/mL). For a bid regimen, Tau=12h.

Characterize PK of asciminib in the Chinese CML-CP population. AUClast is the The AUC from the time of dosing to the time of the last measurable plasma concentration (Tlast) (ng\*hr/mL)

Anti-Infective Agents

Antineoplastic Agents

Antisickling Agents

Fibrinolytic Agents

Platelet Aggregation Inhibitors

Interferons

Hydroxyurea

Anagrelide

Pipobroman

Ruxolitinib was administered at a starting dose of 10 mg twice a day (bid). Dose was adjusted based on efficacy and safety parameters up to a maximum dose of 25 mg bid.

Best Available Therapy as selected by the investigator from: Hydroxyurea, Pegylated-Interferon (IFN/PEG-IFN), pipobroman, anagrelide, IMIDs, or observation. Participants randomized to BAT who did not respond by Week 28 were eligible to crossover and start treatment with ruxolitinib.

Ruxolitinib

This study compared the efficacy and safety of ruxolitinib to Best Available Therapy (BAT) in patients with polycythemia vera (PV) who were hydroxyurea (HU) resistant or intolerant and did not have a palpable spleen.

This was a prospective, multi-center, open-label, randomized, Phase IIIb study evaluating efficacy and safety of ruxolitinib versus BAT as selected by the Investigator in patients with PV who are resistant to, or intolerant of HU.

The study comprised of the following periods:

Screening Period (up to 5 weeks: Day -35 to Day -1): Screening evaluations were performed at one or more clinic visits, and reviewed to determine eligibility before the patient was randomized in the study.

Core Treatment Period (Day 1 to Week 80):

Patients were randomized in 1:1 ratio to either treatment group (ruxolitinib or BAT) and were to be treated with their randomized treatment.

Crossover Treatment Period (Week 28 or after) for BAT patients only:

Patients randomized to BAT who did not respond by Week 28 were eligible to crossover and start treatment with ruxolitinib. Patients crossing over on or after Week 28 had to complete all assessments for the End of Treatment (EoT) visit of the Core Treatment Period followed by the assessments in Cross-over visit evaluation schedule.

Extended Treatment Period (Week 80 to Week 260):

Patients receiving ruxolitinib at Week 80 (including patients who have crossed over from BAT) were eligible to continue up to Week 260 in the Extended Treatment Period. Patients continued the ruxolitinib dose that they received at Week 80. Patients who received BAT at Week 80 were not eligible to enter the Extended Treatment Period and had to have the EoT visit at Week 80 and an End of study (EoS) visit 30 days after the EoT visit.

Follow-up Period:

Patients were followed for safety during 30 days after the last dose of study drug and EoS visit assessments were performed post 30 days after the last dose of study drug. Patients who completed EoT (Week 80 for patients who received BAT, Week 260 for patients who received ruxolitinib or from the time of premature discontinuation) were to be followed-up for every 3 months for survival till the end of the study.

Ruxolitinib Efficacy and Safety in Patients With HU Resistant or Intolerant Polycythemia Vera vs Best Available Therapy.

Randomized, Open Label, Multicenter Phase IIIb Study Evaluating the Efficacy and Safety of Ruxolitinib Versus Best Available Therapy in Patients With Polycythemia Vera Who Are Hydroxyurea Resistant or Intolerant (Response 2)

Proportion of patients achieving Hct control at Week 28 was defined by the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 28, with no more than one phlebotomy eligibility occurring post randomization and prior to Week 8.

Phlebotomy eligibility was defined by:

* Confirmed Hct \> 45% that is at least 3 percentage points higher than the Hct obtained at Baseline Or
* Confirmed Hct \> 48% The confirmation occurred 2 to 14 days subsequent to the initial observation.

Proportion of patients achieving a complete hematological remission at Week 28 was defined by:

* Hct control at Week 28 defined by the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 28, with no more than one phlebotomy eligibility occurring post randomization and prior to Week 8, and
* WBC \< 10 x109/L at Week 28, and
* Platelets ≤ 400 x 109/L at Week 28

Proportion of patients achieving a Hct control at Week 52 was defined by the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 52, and no more than one phlebotomy eligibility occurring post randomization and prior to Week 8

- Endpoint for Week 80 was defined, similarly.

Proportion of patients achieving a complete hematological remission at Week 52, was defined by:

* Hct control at Week 52, as defined by the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 52 with no more than one phlebotomy eligibility occurring post randomization and prior to Week 8, and
* White Blood Count (WBC) \< 10 x10\^9/L at Week 52, and
* Platelets ≤ 400 x 10\^9/L at Week 52
* Endpoint for Week 80 was defined, similarly.

Phlebotomy eligibility was defined by Confirmed Hct \> 45% that is at least 3 percentage points higher than the Hct obtained at Baseline Or Confirmed Hct \> 48%. The confirmation occurred 2 to 14 days subsequent to the initial observation.

Hematocrit is the volume percentage of red blood cells (RBC) in the blood.

Hematocrit is the percentage of red blood cells (RBC) in the blood.

Spleen length was assessed by manual palpation at every study visit.

The ECOG scale of performance status described the level of functioning of participants in terms of their ability to care for themselves, daily activity, and physical ability. The ECOG performance was recorded as per ECOG performance status grades ranging from 0 (fully active, able to carry on all pre-disease performance without restriction) to 5 (dead).

Proportion of patients achieving a partial remission at Week 28, based on the ELN and IWG-MRT criteria, as defined by:

* Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) score reduction of greater than or equal to 10 points from baseline to Week 28, and
* Hct control defined by the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 28, with no more than one phlebotomy eligibility occurring post randomization and prior to Week 8, and
* WBC \< 10 x10\^9/L at Week 28, and
* Platelets ≤ 400 x 10\^9/L at Week 28, and
* No palpable spleen at Week 28, and
* No hemorrhagic or thrombotic events, and
* No transformation into post-PV myelofibrosis, myelodysplastic syndrome (IWG-MRT criteria) or acute leukemia (WHO criteria).

Proportion of patients who achieved partial remission at Week 52 based on the ELN and IWG-MRT criteria, as defined by:

* MPN-SAF TSS score reduction of greater than or equal to 10 points from baseline to Week 52 and
* Hct control defined by the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 52 with no more than one phlebotomy eligibility occurring post randomization and prior to Week 8, and
* WBC \< 10 x109/L at Week 52 and
* Platelets ≤ 400 x 109/L at Week 52 and
* No palpable spleen at Week 52 and
* No hemorrhagic or thrombotic events, and
* No transformation into post-PV myelofibrosis, myelodysplastic syndrome (IWG-MRT criteria) or acute leukemia (WHO criteria).
* Endpoint for Week 80 was defined, similarly.

Proportion of patients achieving a Hct control at Week 104 as defined by the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 104 and with no more than one phlebotomy eligibility occurring post randomization and prior to Week 8 Endpoint for Week 156, Week 208 and Week 260 were defined, similarly.

Proportion of patients achieving a complete hematological remission at Week 104 as defined by Hct control defined by the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 104, with no more than one phlebotomy eligibility occurring post randomization and prior to Week 8, and

* WBC \< 10 x10\^9/L at Week 104, and
* Platelets ≤ 400 x 10\^9/L at Week 104 Endpoint for Week 156, Week 208 and Week 260 were defined, similarly.

Proportion of patients who achieved partial remission at Week 104, based on the ELN and IWG-MRT criteria, as defined by:

* MPN-SAF TSS score reduction of greater than or equal to 10 points from baseline to Week 104, and
* Hct control defined by the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 104, with no more than one phlebotomy eligibility occurring post-randomization and prior to Week 8, and
* WBC \< 10 x10\^9/L at Week 104, and
* Platelets ≤ 400 x 10\^9/L at Week 104, and
* No palpable spleen at Week 104, and
* No hemorrhagic or thrombotic events, and
* No transformation into post-PV myelofibrosis, myelodysplastic syndrome (IWG-MRT criteria) or acute leukemia (WHO criteria) Endpoint for Week 156, Week 208 and Week 260 are defined, similarly.

Transformation-free survival is defined as one of the following:

1. Myelofibrosis (MF) as evidenced by bone marrow biopsy, or
2. Acute leukemia as evidenced by bone marrow blast counts of at least 20%, or peripheral blast counts of at least 20% lasting at least 2 weeks.
3. Death due to any cause during treatment period

Overall survival (OS) event is defined as death due to any cause. OS events were counted in the BAT arm, irrespective of whether participants crossed over to receive ruxolitinib when the event occurred.

The MPN-SAF TSS is a disease specific questionnaire comprised of 10 items that measures fatigue related to MPN disease and the severity of nine of the most prevalent associated symptoms. Each item is scored on a scale ranging from 0 (no fatigue/absent) to 10 (As bad as you can imagine/worst imaginable).The MPN-SAF TSS is computed as the average of the observed items multiplied by 10 to achieve a 0-to-100 scale. The MPN-SAF TSS thus has a possible score range of 0 to 100 where a decrease indicates improvement.

EQ-5D-5L is a standardized instrument for measuring health outcomes in a wide range of health conditions and treatments. It consists of visual analogue scale (EQ VAS) which records the respondent's self-rated health on a vertical, visual analogue scale where the endpoints are labeled 'Best imaginable health state' and 'worst imaginable health state'. The EQ VAS scores were anchored on 100 = the best health you can imagine and 0 = worst health you can imagine.

The Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) is a six item questionnaire which intended to measure work and activity impairment associated with polycythemia vera. WPAI consisted of 6 questions (Q1=Employment status; Q2=Hours absent from work due to the polycythemia vera; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the polycythemia vera on productivity while working; Q6=Impact of the polycythemia vera on productivity while doing regular daily activities other than work). Higher WPAI scores indicated greater activity impairment. Scores were multiplied by 100 to express in percentages.

Percent work time missed due to problem (past 7 days) =Q2/(Q2+Q4) Percent impairment while working due to problem (past 7 days): Q5/10 Percent overall work impairment due to problem (past 7 says): Q2/(Q2+Q4)+\[(1 Q2/(Q2+Q4))x(Q5/10)\] Percent activity impairment due to problem (past 7 says): Q6/10

The Patient Global Impression of Change (PGIC) is comprised of a single question intended to measure a patient's perspective of improvement or deterioration over time relative to treatment. The PGIC uses a seven-point scale where one (1) equals very much improved and seven (7) equals very much worse.

Proportion of participants developing any arterial or venous thromboembolic event

Any signs or symptoms that occured from the day of first dose of study medication to the End of study (End of Treatment +30 days) visit which was Week 260 or prior (+30 days for Rux + crossover) and Week 80 or prior (+30 days for BAT only).

Ruxolitinib at a starting dose of 10 mg twice a day (bid). Dose was adjusted based on efficacy and safety parameters up to a maximum dose of 25 mg bid

Best Available Therapy as selected by the investigator from: Hydroxyurea, Pegylated-Interferon (IFN/PEG-IFN), pipobroman, anagrelide, IMIDs, or observation. Participants randomized to BAT who did not respond by Week 28 were eligible to crossover and start treatment with ruxolitinib

Participants randomized to the BAT arm, who crossed over and received at least one dose of ruxolitinib

All Crossover Patients

Best Available Therapy (BAT)

Race/Ethnicity, Customized

Study Director

Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure.

Number of Participants Achieving Hematocrit (Hct) Control at Week 28

Number of Participants Achieving a Complete Hematological Remission at Week 28

Week 52

Week 80

Number of Participants Achieving a Hematocrit (Hct) Control at Week 52 and Week 80

Number of Participants Achieving a Complete Hematological Remission at Week 52 and Week 80

Phlebotomy frequency: >0 - <=2

Phlebotomy frequency: >2 - <=4

Phlebotomy frequency: >4 - <=6

Phlebotomy frequency: >6 - <=8

Number of Participants With Phlebotomies Over Time

Week 4

Week 8

Week 12

Week 16

Week 20

Week 24

Week 28

Week 40

Week 66

Week 92

Week 104

Week 117

Week 130

Week 143

Week 156

Week 169

Week 182

Week 195

Week 208

Week 221

Week 234

Week 247

Week 260

Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure. Data after crossover for participants randomized to BAT are reported as separate outcome measure.

Change From Baseline in Hematocrit (Hct) at Each Visit

Week +4

Week +8

Week +12

Week +16

Week +20

Week +24

Week +28

Week +40

Week +52

Week +64

Week +76

Cross-over set consisted of all participants randomized to the BAT arm, who crossed over and received at least one dose of ruxolitinib.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pacritinib Versus Best Available Therapy to Treat Patients With Myelofibrosis and Thrombocytopenia	NCT02055781	Primary Myelofi... Post-polycythem... Post-essential ...	Pacritinib Best Available ...	18 Years -	CTI BioPharma
Study of Efficacy and Safety of CML-CP Patients Treated With Asciminib Versus Best Available Therapy, Previously Treated With 2 or More Tyrosine Kinase Inhibitors	NCT04795427	Leukemia, Chron...	asciminib best available ...	18 Years -	Novartis
Ruxolitinib Efficacy and Safety in Patients With HU Resistant or Intolerant Polycythemia Vera vs Best Available Therapy.	NCT02038036	Polycythemia Ve...	Best Available ... Ruxolitinib	18 Years -	Novartis
Ruxolitinib Efficacy and Safety in Patients With HU Resistant or Intolerant Polycythemia Vera vs Best Available Therapy.	NCT02038036	Polycythemia Ve...	Best Available ... Ruxolitinib	18 Years -	Novartis
Pacritinib Versus Best Available Therapy to Treat Patients With Myelofibrosis and Thrombocytopenia	NCT02055781	Primary Myelofi... Post-polycythem... Post-essential ...	Pacritinib Best Available ...	18 Years -	CTI BioPharma
Study to Assess Efficacy and Safety of NS-018 Compared to BAT in Patients With Myelofibrosis	NCT04854096	Primary Myelofi... Post-essential ... Post-polycythem...	NS-018 Best Available ...	18 Years -	NS Pharma, Inc.

Spots Global Cancer Trial Database for best available therapy