Safety and Tolerability Study of Mivebresib Tablet Alone or in Combination With Ruxolitinib Tablet or Navitoclax Tablet in Adult Participants With Myelofibrosis
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|ClinicalTrials.gov Identifier: NCT04480086|
Recruitment Status : Active, not recruiting
First Posted : July 21, 2020
Last Update Posted : May 19, 2021
Myelofibrosis (MF) is a bone marrow illness that affects blood-forming tissues in the body. MF disturbs the body's normal production of blood cells, causing extensive scarring in the bone marrow. This leads to severe anemia, weakness, fatigue, and an enlarged spleen. The purpose of this study is to see how safe and tolerable mivebresib is, when given alone, and in combination with navitoclax or ruxolitinib, for adult participants with MF.
Mivebresib is an investigational drug being developed for the treatment of MF. The study has 4 segments - A, B, C, and D. In Segment A, the safe dosing regimen of mivebresib is identified, and then given alone as monotherapy. In Segment B, C, and D, combination therapies of mivebresib with either ruxolitinib or navitoclax are given. Adult participants with a diagnosis of MF will be enrolled. Around 130 participants will be enrolled in 60 sites worldwide.
In Segment A, participants will receive different doses and schedules of oral mivebresib tablet to identify a safe dosing regimen. Additional participants will be enrolled at the identified monotherapy dosing regimen. In Segment B, participants will receive oral ruxolitinib and mivebresib will be given as "add-on" therapy. In Segment C, participants will receive mivebresib and oral navitoclax. In Segment D, participants will receive mivebresib and ruxolitinib. Participants will receive treatment until disease progression or the participants are not able to tolerate the study drugs.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of treatment will be checked by medical assessments, blood and bone marrow tests, checking for side effects, and completing questionnaires.
|Condition or disease||Intervention/treatment||Phase|
|Myelofibrosis (MF)||Drug: Mivebresib Drug: Navitoclax Drug: Ruxolitinib||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||1 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1b Study of Mivebresib Alone or in Combination With Ruxolitinib or Navitoclax in Subjects With Myelofibrosis|
|Actual Study Start Date :||March 17, 2021|
|Estimated Primary Completion Date :||June 15, 2022|
|Estimated Study Completion Date :||June 15, 2022|
Experimental: Segment A: Mivebresib Dose Identification and Optimization
Participants who have been previously treated with Janus Kinase inhibitor(s) (JAKi) and stopped such therapy, will receive different dosing regimens and schedules of mivebresib to identify the safe dosing regimen and schedule.
Experimental: Segment A: Mivebresib Monotherapy
Participants will receive the identified safe dosing regimen of mivebresib as monotherapy.
Experimental: Segment B: Ruxolitinib + Mivebresib "Add-on" Therapy
Participants whose disease (myelofibrosis) is inadequately controlled by ongoing ruxolitinib therapy will receive ruxolitinib and mivebresib as "add-on" therapy.
Experimental: Segment C: Mivebresib + Navitoclax
Participants who have previously been exposed to JAKi, and stopped such therapy, will receive mivebresib and navitoclax.
Other Name: ABT-263
Experimental: Segment D: Mivebresib + Ruxolitinib
Participants who have never received JAKi will receive mivebresib and ruxolitinib.
- Percentage of Participants With Adverse Events [ Time Frame: Up To Approximately 1 year from start of study ]An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with the treatment. The investigator assesses the relationship of each event to the use of study drug.
- Percentage of Participants who Achieve Spleen Volume Reduction of 35% or Greater (SVR35) [ Time Frame: Up To Week 24 ]Reduction in spleen volume is measured by magnetic resonance imaging (MRI).
- Maximum Observed Plasma Concentration (Cmax) of Mivebresib [ Time Frame: Up To Week 12 ]Maximum observed plasma concentration (Cmax) of Mivebresib.
- Time to Cmax (Tmax) of Mivebresib [ Time Frame: Up To Week 12 ]The amount of time taken to reach Cmax.
- Area Under Concentration vs Time Curve (AUC) of Mivebresib [ Time Frame: Up To Week 12 ]AUC of Mivebresib will be calculated.
- Half-Life (t1/2) of Mivebresib [ Time Frame: Up To Week 12 ]Half-life of Mivebresib will be calculated.
- Accumulation Ratio of Mivebresib [ Time Frame: Up To Week 12 ]Pharmacokinetic parameters will include accumulation ratio of Mivebresib.
- Apparent Clearance (CL/F) of Mivebresib [ Time Frame: Up To Week 12 ]CL/F of Mivebresib will be calculated.
- Apparent Volume of Distribution (Vd/F) of Mivebresib [ Time Frame: Up To Week 12 ]Vd/F of mivebresib will be calculated.
- Percentage of Participants With >= 50% Reduction in Total Symptom Score (TSS) [ Time Frame: Week 24 ]TSS is assessed using the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0. MFSAF v4.0 measures the burden of myelofibrosis-related symptoms. The symptoms are assessed on a 11-point numeric rating scale (NRS) anchored from 0 (absent) to 10 (worst imaginable).
- Objective Response Rate (ORR) [ Time Frame: Week 24 ]ORR is defined as the sum of rates of complete remission (CR) and partial remission (PR).
- Maximum Observed Plasma Concentration (Cmax) of Navitoclax [ Time Frame: Up To Week 12 ]Maximum Observed Plasma Concentration (Cmax) Of Navitoclax.
- Time to Cmax (Tmax) of Navitoclax [ Time Frame: Up To Week 12 ]The amount of time taken to reach Cmax.
- Area Under Concentration vs Time Curve (AUC) of Navitoclax [ Time Frame: Up To Week 12 ]AUC of Navitoclax will be calculated.
- Maximum Observed Plasma Concentration (Cmax) of Ruxolitinib [ Time Frame: Up To Week 12 ]Maximum Observed Plasma Concentration (Cmax) Of Ruxolitinib.
- Time to Cmax (Tmax) of Ruxolitinib [ Time Frame: Up To Week 12 ]The amount of time taken to reach Cmax.
- Area Under Concentration vs Time Curve (AUC) of Ruxolitinib [ Time Frame: Up To Week 12 ]AUC of Ruxolitinib will be calculated.
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): NCT04480086
|United States, New York|
|Stony Brook University Hospital /ID# 222653|
|Stony Brook, New York, United States, 11794-8183|
|United States, Ohio|
|UC Health - Cincinnati /ID# 224079|
|Cincinnati, Ohio, United States, 45267-2800|
|United States, Tennessee|
|Thompson Cancer Survival Ctr /ID# 225802|
|Knoxville, Tennessee, United States, 37916|
|United States, Texas|
|University of Texas MD Anderson Cancer Center /ID# 221652|
|Houston, Texas, United States, 77030|
|United States, Washington|
|VA Puget Sound Health Care System /ID# 224234|
|Seattle, Washington, United States, 98108-1532|
|Hospital Italiano de Buenos Aires /ID# 226946|
|Ciudad Autonoma Buenos Aires, Buenos Aires, Argentina, 1199|
|Hospital Universitario Austral /ID# 228910|
|Pilar, Argentina, 1629|
|Korea, Republic of|
|Inje University Busan Paik Hospital /ID# 224043|
|Busan, Gyeongsangbugdo, Korea, Republic of, 47392|
|Wits Health Consortium (Pty) Ltd /ID# 222669|
|Johannesburg, Gauteng, South Africa, 1864|
|Albert Alberts Stem Cell Transplant Centre /ID# 222667|
|Pretoria, Gauteng, South Africa, 0044|
|University of Cape Town /ID# 222666|
|Cape Town, Western Cape, South Africa, 7925|
|Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi /ID# 227711|
|Ankara, Turkey, 06200|
|Koç Üniversitesi Hastanesi Translasyonel Tıp Araştırma Merkezi /ID# 227712|
|Istanbul, Turkey, 34010|
|Dokuz Eylul University Medical Faculty /ID# 227710|
|Izmir, Turkey, 35340|
|Study Director:||ABBVIE INC.||AbbVie|