ABBV-744 + Ruxolitinib/Navitoclax for Myelofibrosis

Recruiting in Palo Alto (17 mi)

+66 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: AbbVie

No Placebo Group

Trial Summary

What is the purpose of this trial?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 ABBV-744 is, when given alone, and in combination with ruxolitinib or navitoclax, for adult participants with MF. ABBV-744 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 ABBV-744 is identified and then, given alone as monotherapy. In Segment B, C, and D, combination therapies of ABBV-744 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 ABBV-744 tablet to identify safe dosing regimen. Additional participants will be enrolled at the identified monotherapy dosign regimen. In Segment B, participants will receive oral ruxolitinib and ABBV-744 will be given as "add-on" therapy. In Segment C, participants will receive ABBV-744 and oral navitoclax. In Segment D, participants will receive ABBV-744 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.

Eligibility Criteria

Adults with Myelofibrosis (MF), a bone marrow disorder, can join this trial. They must have tried a JAK inhibitor treatment before and either didn't respond well or it stopped working. Their spleen should be enlarged, they need to be in decent physical shape (ECOG <=2), and their organs must function adequately as per specific lab values.

Inclusion Criteria

My spleen is enlarged, confirmed by a scan.

My condition is considered intermediate-2 or high-risk, or I have a significantly enlarged spleen.

I have been diagnosed with a serious form of myelofibrosis.

+7 more

Participant Groups

The study tests ABBV-744's safety alone or combined with ruxolitinib/navitoclax in treating MF. It has four parts: finding the safe dose of ABBV-744; then testing it with ruxolitinib ('add-on' therapy); combining it with navitoclax; and another combination regimen with ruxolitinib.

5Treatment groups

Experimental Treatment

Group I: Segment D: ABBV-744 + RuxolitinibExperimental Treatment2 Interventions

Participants who have never received JAKi will receive ABBV-744 and ruxolitinib.

Group II: Segment C: ABBV-744 + NavitoclaxExperimental Treatment2 Interventions

Participants who have previously been exposed to JAKi, and stopped such therapy, will receive ABBV-744 and navitoclax.

Group III: Segment B: Ruxolitinib + ABBV-744 "Add on" TherapyExperimental Treatment2 Interventions

Participants whose disease (myelofibrosis) is inadequately controlled by ongoing ruxolitinib therapy will receive ruxolitinib and ABBV-744 as "add-on" therapy.

Group IV: Segment A: ABBV-744 MonotherapyExperimental Treatment1 Intervention

Participants will receive the identified safe dosing regimen of ABBV-744 as monotherapy.

Group V: Segment A: ABBV-744 Dose Identification and OptimizationExperimental Treatment1 Intervention

Participants who have been previously treated with Janus Kinase inhibitor(s) (JAKi) and stopped such therapy, will receive different dosing regimens and schedules of ABBV-744 to identify the safe dosing regimen and schedule.