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Myelofibrosis (MF)Phase 1NCT04480086

Safety and Tolerability Study of Mivebresib Tablet Alone or in Combination With Ruxolitinib Tablet or Navitoclax Tablet in Adult Participants With Myelofibrosis

A Phase 1 study testing Mivebresib, Navitoclax and Ruxolitinib in people with Myelofibrosis (MF), run by AbbVie at 7 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Myelofibrosis (MF)
What is being tested?
Mivebresib, Navitoclax and Ruxolitinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
7 sitesin 3 countries
Study dates
17 Mar 2021to 28 Jul 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Laboratory values indicative of adequate bone marrow, renal, and hepatic function meeting protocol criteria
  • Completion of the Myelofibrosis System Assessment Form (MFSAF) on at least 4 out of the 7 days prior to Day 1 with at least 2 symptoms with a score >=3 or a total score of >=10.
  • Documented diagnosis of intermediate or high-risk primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF) or post-essential thrombocytopenia myelofibrosis (PET-MF) as defined by World Health Organization (WHO).
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
  • Intermediate - 2, or High-Risk disease as defined by the Dynamic International Prognostic Scoring System (For Segment A only, Intermediate - 1 with palpable splenomegaly >=5 centimeters [cm] below costal margin are also eligible).
  • Splenomegaly defined as spleen palpation measurement >= 5 centimeters (cm) below costal margin or spleen volume >= 450 cubic cms as assessed by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT) scan (for Segments A and c, baseline spleen assessment must be obtained > 7 days after discontinuation of most recent Myelofibrosis (MF) therapy. If possible, this assessment should occur within 10 days of Cycle 1 Day 1).
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  • Segment-Specific Prior Therapy Criteria:
  • Segment A:
  • --Prior exposure to one or more Janus Kinase Inhibitors (JAKi), the most recent of which was discontinued > 28 days prior to Cycle 1 Day 1.
  • Segment B:
  • Currently receiving ruxolitinib; AND
  • Willingness to reduce dose (if on a higher dose); and on a stable dose for 14 days or longer prior to Cycle 1 Day 1; AND
  • At least one of the following criteria (a, b, or c):
  • >= 24 weeks duration of current ruxolitinib course, with evidence of disease that is resistant, refractory, or has lost response to ruxolitinib monotherapy;
  • < 24 weeks duration of current ruxolitinib course with documented disease progression as defined by any of the following:
  • Appearance of new splenomegaly that is palpable to at least 5 centimeters (cm) below the left costal margin (LCM), in participants with no evidence of splenomegaly prior to the initiation of ruxolitinib.
  • 100% increase in the palpable distance below the LCM, in participants with measurable spleen distance 5 - 10 cm prior to the initiation of ruxolitinib.
  • 50% increase in the palpable distance below the LCM, in participants with measurable spleen > 10 cm prior to the initiation of ruxolitinib.
  • A spleen volume increase >= 25% (as assessed by MRI or CT) in participants with a spleen volume assessment available prior to the initiation of ruxolitinib.
  • Prior treatment with ruxolitinib for >= 28 days complicated by any of the following:
  • Development of red blood cell transfusion requirement (at least 2 units/month for 2 months).
  • Grade >= 3 adverse events of neutropenia and/or anemia while on ruxolitinib treatment, with improvement or resolution upon dose reduction.
  • Segment C:
  • Prior exposure to one or more JAKi (the most recent of which was discontinued > 28 days prior to Cycle 1 Day 1), and are intolerant, resistant, refractory or lost response to teh JAKi.

Who cannot join

  • Segment-Specific Prior Therapy Criteria:
  • Segment A:
  • --Prior exposure to one or more Bromodomain and Extra Terminal (BET) inhibitors.
  • Segment B:
  • --Prior exposure to one or more BET inhibitors.
  • Segment C:
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  • --Prior exposure to one or more BET inhibitors and/or any B-Cell Lymphoma 2 (BCL2) and/or B-Cell Lymphoma XL (BCLXL) inhibitor, including navitoclax.
  • Segment D:
  • Prior exposure to JAKi and/or any BET inhibitor.

Trial locations and contacts

7 sites in 3 countries.

7 sites in 3 countries

United States4 sites

  • UC Health - Cincinnati /ID# 224079

    Cincinnati, Ohio, 45267-2800

  • University of Texas MD Anderson Cancer Center /ID# 221652

    Houston, Texas, 77030

  • Thompson Cancer Survival Ctr /ID# 225802

    Knoxville, Tennessee, 37916

  • Stony Brook University Hospital /ID# 222653

    Stony Brook, New York, 11794-8183

Other trials in United States

South Africa2 sites

  • Wits Clinical Research , Wits Health Consortium (PTY) Ltd /ID# 222669

    Johannesburg, Gauteng, 2193

  • Alberts Cellular Therapy /ID# 222667

    Pretoria, Gauteng, 0044

Other trials in South Africa

South Korea1 site

  • Inje University Busan Paik Hospital /ID# 224043

    Busan, 47392

Other trials in South Korea

About this study

Official title: A Phase 1b Study of Mivebresib Alone or in Combination With Ruxolitinib or Navitoclax in Subjects With Myelofibrosis

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.

Read more

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.

Being tested
Mivebresib, Navitoclax, Ruxolitinib
Keywords
mivebresib, Navitoclax, Ruxolitinib, ABT-263, Cancer, Myelofibrosis, MF, ABBV-075
Medical subject headings
Primary Myelofibrosis, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MivebresibDrug

    Tablet: Oral

  • NavitoclaxDrug

    Also called ABT-263

    Tablet; Oral

  • RuxolitinibDrug

    Tablet; Oral

Study groups in NCT04480086
Study groupRoleWhat they receive
Segment A: Mivebresib Dose Identification and OptimizationExperimentalParticipants 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.
Receives: Drug: Mivebresib
Segment A: Mivebresib MonotherapyExperimentalParticipants will receive the identified safe dosing regimen of mivebresib as monotherapy.
Receives: Drug: Mivebresib
Segment B: Ruxolitinib + Mivebresib "Add-on" TherapyExperimentalParticipants whose disease (myelofibrosis) is inadequately controlled by ongoing ruxolitinib therapy will receive ruxolitinib and mivebresib as "add-on" therapy.
Receives: Drug: Mivebresib; Drug: Ruxolitinib
Segment C: Mivebresib + NavitoclaxExperimentalParticipants who have previously been exposed to JAKi, and stopped such therapy, will receive mivebresib and navitoclax.
Receives: Drug: Mivebresib; Drug: Navitoclax
Segment D: Mivebresib + RuxolitinibExperimentalParticipants who have never received JAKi will receive mivebresib and ruxolitinib.
Receives: Drug: Mivebresib; Drug: Ruxolitinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With Adverse Events

    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.

    Measured: Up To Approximately 1 year from start of study

Secondary outcomes (16)

  1. Percentage of Participants who Achieve Spleen Volume Reduction of 35% or Greater (SVR35)

    Reduction in spleen volume is measured by magnetic resonance imaging (MRI).

    Measured: Up To Week 24

  2. Maximum Observed Plasma Concentration (Cmax) of Mivebresib

    Maximum observed plasma concentration (Cmax) of Mivebresib.

    Measured: Up To Week 12

  3. Time to Cmax (Tmax) of Mivebresib

    The amount of time taken to reach Cmax.

    Measured: Up To Week 12

  4. Area Under Concentration vs Time Curve (AUC) of Mivebresib

    AUC of Mivebresib will be calculated.

    Measured: Up To Week 12

  5. Half-Life (t1/2) of Mivebresib

    Half-life of Mivebresib will be calculated.

    Measured: Up To Week 12

  6. Accumulation Ratio of Mivebresib

    Pharmacokinetic parameters will include accumulation ratio of Mivebresib.

    Measured: Up To Week 12

  7. Apparent Clearance (CL/F) of Mivebresib

    CL/F of Mivebresib will be calculated.

    Measured: Up To Week 12

  8. Apparent Volume of Distribution (Vd/F) of Mivebresib

    Vd/F of mivebresib will be calculated.

    Measured: Up To Week 12

  9. Percentage of Participants With >= 50% Reduction in Total Symptom Score (TSS)

    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).

    Measured: Week 24

  10. Objective Response Rate (ORR)

    ORR is defined as the sum of rates of complete remission (CR) and partial remission (PR).

    Measured: Week 24

  11. Maximum Observed Plasma Concentration (Cmax) of Navitoclax

    Maximum Observed Plasma Concentration (Cmax) Of Navitoclax.

    Measured: Up To Week 12

  12. Time to Cmax (Tmax) of Navitoclax

    The amount of time taken to reach Cmax.

    Measured: Up To Week 12

  13. Area Under Concentration vs Time Curve (AUC) of Navitoclax

    AUC of Navitoclax will be calculated.

    Measured: Up To Week 12

  14. Maximum Observed Plasma Concentration (Cmax) of Ruxolitinib

    Maximum Observed Plasma Concentration (Cmax) Of Ruxolitinib.

    Measured: Up To Week 12

  15. Time to Cmax (Tmax) of Ruxolitinib

    The amount of time taken to reach Cmax.

    Measured: Up To Week 12

  16. Area Under Concentration vs Time Curve (AUC) of Ruxolitinib

    AUC of Ruxolitinib will be calculated.

    Measured: Up To Week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jul 2020
  2. Study start17 Mar 2021
  3. Primary completion28 Jul 2023
  4. Study completion28 Jul 2023

Why it stopped: Strategic considerations

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04480086
Sponsor's protocol ID
M20-248
Other IDs
2020-001226-65
Status last verified
Aug 2023
First submitted
20 Jul 2020
Last updated
29 Aug 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Mivebresib, Navitoclax and Ruxolitinib in people with Myelofibrosis (MF), run by AbbVie at 7 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 29 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States, South Africa, South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Strategic considerations). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Adverse Events (time frame: Up To Approximately 1 year from start of study). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04480086.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Aug 2023.

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