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Bcl-2 Inhibitor

Navitoclax + Ruxolitinib for Myeloproliferative Disorders

Phase 1

Waitlist Available

Research Sponsored by AbbVie

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Must have received ruxolitinib therapy for at least 12 weeks and be currently on a stable dose of ruxolitinib (as described in the protocol).

Classified as intermediate-2 or high-risk MF, as defined by the Dynamic International Prognostic Scoring System (DIPSS).

Must not have

Had prior therapy with a BH3 mimetic compound or BET inhibitor.

Have accelerated MF, defined as > 10% blasts in peripheral blood or bone marrow aspirate and biopsy.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from first dose of study drug until 30 days following last dose of study drug (up to approximately 5 years).

Awards & highlights

No Placebo-Only Group

Summary

This trial has 4 parts to evaluate the safety and how well the drug navitoclax works when given alone or with another drug, ruxolitinib. The trial will also look at how navitoclax affects QTc prolongation and how it affects the PK, safety, and tolerability of celecoxib in people with MPN or CMML.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects include changes in blood counts leading to increased risk of bleeding or infection, liver function alterations, gastrointestinal symptoms like nausea or diarrhea, fatigue, potential heart rhythm changes (QTc prolongation), as well as possible interactions that could affect how other medications work.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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

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

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

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

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

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

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

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I have been diagnosed with myelofibrosis according to WHO standards.

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

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

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

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

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

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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

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

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

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I have taken a BH3 mimetic drug before.

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

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

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

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

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I am eligible for a stem cell transplant.

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I have been treated with a BH3 mimetic before.

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

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from first dose of study drug until 30 days following last dose of study drug (up to approximately 5 years).

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from first dose of study drug until 30 days following last dose of study drug (up to approximately 5 years).

This trial's timeline: 3 weeks for screening, Varies for treatment, and from first dose of study drug until 30 days following last dose of study drug (up to approximately 5 years). for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Area Under the Plasma Concentration-time Curve from time 0 to the time of the last measurable concentration (AUCt) of Celecoxib (Part 4)

Area Under the Plasma Concentration-time Curve from time 0 to the time of the last measurable concentration (AUCt) of Navitoclax

Change in QT interval corrected for heart rate interval by Fridericia's correction formula (QTcF) (Part 3)

+6 more

Secondary study objectives

Overall Response Rate

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

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).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug