Pacritinib + Venetoclax + Azacitidine for Myeloproliferative Neoplasms

AR
Overseen ByASK ROSWELL
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: Roswell Park Cancer Institute
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of drugs—pacritinib, venetoclax, and azacitidine—to determine the optimal dose and assess side effects in treating advanced-stage myeloproliferative neoplasms, a type of blood cancer. The goal is to evaluate whether these drugs can safely and effectively inhibit cancer cell growth. Individuals with a previous diagnosis of certain blood disorders, now in an advanced stage, may be suitable candidates for this trial. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research is examining the effectiveness and optimal dosing of a combination of three drugs: pacritinib, venetoclax, and azacitidine. Earlier studies showed that pacritinib with azacitidine might be safe and manageable for patients. Venetoclax with azacitidine carries some risks, such as reducing blood cell production, but also shows promise in treating certain blood cancers.

In this trial's early stages, researchers focus on safety and determining the right dose. This phase assesses how well patients tolerate the treatment and identifies any side effects. While there is potential, the safety of this combination remains under study.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Pacritinib, Venetoclax, and Azacitidine because it targets myeloproliferative neoplasms in a unique way. Unlike traditional treatments that may focus on one pathway, this combination targets multiple pathways involved in cancer cell growth and survival. Pacritinib is a selective kinase inhibitor, Venetoclax disrupts proteins that prevent cancer cell death, and Azacitidine affects DNA methylation. This multi-pronged approach has the potential to be more effective and may overcome resistance seen with single-agent therapies.

What evidence suggests that this trial's treatments could be effective for myeloproliferative neoplasms?

Research has shown that the combination of pacritinib, venetoclax, and azacitidine, which participants in this trial will receive, may effectively treat advanced stages of myeloproliferative neoplasms, a type of blood cancer. Studies have found that using azacitidine and venetoclax together can lead to a 77% overall response rate, with 42% of patients experiencing complete remission. Additionally, pacritinib and azacitidine may stop cancer cells from growing by blocking the enzymes they need. This combination has also proven effective and well-tolerated in patients with different genetic types of acute myeloid leukemia (AML). These findings suggest that the treatment might work for similar conditions, such as accelerated and blast phase myeloproliferative neoplasms.12678

Who Is on the Research Team?

SG

Steven Green, MD

Principal Investigator

Roswell Park Comprehensive Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with accelerated or blast phase myeloproliferative neoplasms (a type of blood cancer). Participants should be able to undergo treatment and tests, but specific inclusion and exclusion criteria are not detailed here.

Inclusion Criteria

Participants of child-bearing potential must agree to use highly effective contraception and report pregnancy immediately
I have MPN with 10% or more blasts and was previously diagnosed with ET, PV, or PMF.
My recent lab tests show my organs are working well enough for treatment.
See 4 more

Exclusion Criteria

I have not recently taken strong CYP3A4 inhibitor or inducer medications.
Baseline prolonged QTc > 480 msec by Fridericia's formula; repeat EKG allowed after correction
I do not have digestive issues that affect medicine absorption.
See 13 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pacritinib, venetoclax, and azacitidine in cycles of 28 days for up to 12 cycles

12 cycles (28 days each)
Regular visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Up to 1 year
Follow-up at 30 days post-treatment, then every 3 months

What Are the Treatments Tested in This Trial?

Interventions

  • Azacitidine
  • Pacritinib
  • Venetoclax

Trial Overview

Researchers are testing the safety and best dose of pacritinib when combined with venetoclax and azacitidine in people with advanced myeloproliferative neoplasms. The study uses imaging scans and bone marrow tests to monitor effects.

How Is the Trial Designed?

1

Treatment groups

Experimental Treatment

Group I: Treatment Arm 1Experimental Treatment6 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

Roswell Park Cancer Institute

Lead Sponsor

Trials
427
Recruited
40,500+

Citations

Phase I Trial of Pacritinib in Combination With Venetoclax ...

Pacritinib and azacitidine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Venetoclax with azacitidine or decitabine in blast‐phase ...

Although overall median survival was only 3.6 months, the 3‐year survival rate was significantly higher (32%) among 24 patients who received allogeneic ...

Azacitidine, Venetoclax, Ruxolitinib Shows Encouraging ...

The overall response rate was 80%, and the complete remission (CR) rate was 40%. The median overall survival was 13.4 months (95% CI, 4.2-13.4), ...

Phase I Trial of Pacritinib in Combination With Venetoclax ...

Pacritinib and azacitidine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Dr Marvin-Peek on the Significance of Efficacy Data ...

Among evaluable patients in the trial (n = 40), overall response rates (ORR) with azacitidine, plus venetoclax and ivosidenib was 95%. Moreover, ...

Chemotherapy-Ineligible Patients With AML May Benefit ...

The median overall survival period was 14.7 months in the venetoclax plus azacitidine cohort vs 9.6 months with placebo plus azacitidine.

Single-center experience with venetoclax combinations in ...

Venetoclax-based therapy was associated with significant myelosuppression and mortality, with a median survival of 4 months.

Pacritinib, Venetoclax, and Azacitidine Combination for ...

This study aims to determine the maximum tolerated dose of a treatment regimen combining Pacritinib, Venetoclax, and Azacitidine for individuals