Navitoclax + Ruxolitinib for Myeloproliferative Disorders

Palo Alto (17 mi)

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?There are 5 parts to this study for which the primary objectives are to evaluate safety, tolerability, and pharmacokinetics (PK) of navitoclax when administered alone (Part 1) or when administered in combination with ruxolitinib (Part 2). In Part 2, participants must have been receiving a stable dose of ruxolitinib therapy for at least 12 weeks prior to study enrollment. In Part 3, all eligible participants will receive navitoclax, with the primary objective being to evaluate potential navitoclax effect on QTc prolongation. In Part 4, effect of navitoclax is evaluated on the PK, safety, and tolerability of a single dose of celecoxib. In Part 5, all eligible participants will receive ruxolitinib twice daily and navitoclax once daily for drug-drug interaction (DDI) assessment, followed by continued administration of navitoclax in combination with ruxolitinib.

Eligibility Criteria

This trial is for adults with myeloproliferative disorders who've failed or can't tolerate standard treatments and aren't eligible for stem cell transplantation. They must have stable vital organ functions, an ECOG performance status of <=2 (<=1 in some parts), and specific blood values within range. People with active hepatitis B/C, HIV, recent use of certain drugs affecting coagulation or metabolism, leukemic transformation, or other malignancies within the last 2 years are excluded.

Inclusion Criteria

I have been on ruxolitinib for at least 12 weeks and my dose hasn't changed recently.

My myelofibrosis is classified as intermediate-2 or high-risk.

I need treatment and have either not responded to or cannot tolerate at least one prior therapy, or I refuse standard therapy.

I am able to get out of my bed or chair and move around.

My spleen is enlarged, either felt below my ribs or confirmed by a scan.

I have been diagnosed with a specific type of blood cancer.

I can take care of myself but might not be able to do heavy physical work.

I have been diagnosed with a type of myelofibrosis according to WHO standards.

I have been diagnosed with myelofibrosis according to WHO standards.

I have been diagnosed with myelofibrosis, polycythemia vera, or essential thrombocythemia.

I am fully active and can carry on all pre-disease activities without restriction.

I cannot or do not want to have a stem cell transplant.

I need treatment for myelofibrosis and have either not been treated with a JAK2 inhibitor or have only been treated with ruxolitinib.

I have tried ruxolitinib for myelofibrosis and it didn't work or caused side effects.

Exclusion Criteria

I have been treated with a BH3 mimetic or BET inhibitor before.

My blood or bone marrow has more than 10% blast cells.

My blood tests show a high number of immature blood cells.

I haven't taken strong medications like ketoconazole within the last 2 weeks.

I have taken a BH3 mimetic drug before.

My blood or bone marrow shows signs of turning into leukemia.

I have not taken CYP2C9 inhibitors in the last 28 days or within their half-life period.

I have other serious health conditions that are not under control.

I am receiving treatment for chronic active hepatitis B or C.

I am eligible for a stem cell transplant.

I have been treated with a BH3 mimetic before.

I am taking blood thinners other than low-dose aspirin or LMWH.

Treatment Details

The study tests Navitoclax alone and combined with Ruxolitinib to assess safety and how the body processes these drugs in people with myeloproliferative neoplasms. It's divided into five parts: solo Navitoclax effects; its combination with ongoing Ruxolitinib treatment; impact on heart rhythm; interaction with Celecoxib; and a drug-drug interaction assessment followed by extended combination therapy.

5Treatment groups

Experimental Treatment

Group I: Part 5: Navitoclax + Ruxolitinib Combination TherapyExperimental Treatment2 Interventions

Participants will receive ruxolitinib BID and navitoclax QD for drug-drug interaction (DDI) assessment, followed by continued administration of navitoclax in combination with ruxolitinib.

Group II: Part 4: Navitoclax + CelecoxibExperimental Treatment2 Interventions

Participants will receive navitoclax once daily (QD) starting on Day 3. Participants will also receive celecoxib single dose on Day 1 and Day 7.

Group III: Part 3: Navitoclax MonotherapyExperimental Treatment1 Intervention

Participants will receive navitoclax once daily (QD).

Group IV: Part 2: Navitoclax + Ruxolitinib Combination TherapyExperimental Treatment2 Interventions

Participants will receive various doses of navitoclax once daily (QD) in combination with ruxolitinib twice daily (BID).

Group V: Part 1: Navitoclax MonotherapyExperimental Treatment1 Intervention

Participants will receive various doses of navitoclax once daily (QD).