What side effects are associated with this type of intervention?

Ruxolitinib, a JAK1/2 inhibitor used in the treatment of Polycythemia Vera, commonly causes side effects such as anemia, thrombocytopenia, and increased risk of infections. Other potential adverse effects include headaches, dizziness, and elevated liver enzymes. PI3K delta inhibitors, like TGR-1202, can lead to gastrointestinal symptoms (e.g., diarrhea, nausea), liver toxicity, and increased risk of infections. Both treatments require careful monitoring and dose adjustments to manage these side effects effectively.

What prior FDA approvals exist?

Ruxolitinib, a JAK1/2 inhibitor, has been FDA-approved for the treatment of Polycythemia Vera, especially for patients who are resistant or intolerant to hydroxyurea. This approval highlights its efficacy in managing PV by reducing splenomegaly and controlling hematocrit levels. While TGR-1202, a PI3K delta inhibitor, is being studied in combination with Ruxolitinib for myeloproliferative neoplasms, there are no specific FDA approvals for PI3K inhibitors in the treatment of PV as of now.

What other types of research exist?

Promising novel alternatives for Polycythemia Vera patients in 2024 include Fedratinib (a JAK2 inhibitor) and Imetelstat (a telomerase inhibitor). Both have shown efficacy in treating myeloproliferative neoplasms and are under investigation for their potential benefits in PV.

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JAK1/2 inhibitor

TGR-1202 + Ruxolitinib for Polycythemia Vera

Q: What is the mechanism of action of this treatment?

Ruxolitinib, a JAK1/2 inhibitor, works by blocking the Janus kinase (JAK) pathway, which is often overactive in PV due to mutations like JAK2 V617F. This inhibition reduces the excessive production of blood cells, alleviating symptoms and reducing spleen size. TGR-1202, a PI3K delta inhibitor, targets the PI3K/AKT/mTOR pathway, which is involved in cell growth and survival. By inhibiting this pathway, TGR-1202 can help control abnormal cell proliferation. These mechanisms are crucial for PV patients as they address the underlying causes of the disease, helping to manage symptoms and prevent complications such as thrombosis and progression to myelofibrosis.

Phase 1

Waitlist Available

Led By Michael Savona, MD

Research Sponsored by Vanderbilt-Ingram Cancer Center

Eligibility Criteria Checklist

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

Must have

Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2

Must have adequate organ function as demonstrated by specific laboratory values

Must not have

Other invasive malignancies within the last 2 years, except non-melanoma skin cancer and localized cured prostate, cervical cancer, and DCIS

History of cerebral vascular accident, unstable angina, myocardial infarction, or ventricular arrhythmia within the last 6 months

Timeline

Screening 3 weeks

Treatment Varies

Follow Up </=12 months

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new drug, TGR-1202, combined with an existing drug, ruxolitinib, in patients with certain blood cancers who are not responding to current treatments. The goal is to see if blocking two different pathways can better stop cancer cell growth. Ruxolitinib is the first approved treatment for myelofibrosis and has shown efficacy in reducing spleen size and improving quality of life.

Who is the study for?

This trial is for adults with certain blood disorders (polycythemia vera, primary myelofibrosis, or MDS/MPN) who have not responded well to standard treatments like hydroxyurea or are newly diagnosed. Participants must be in stable health as indicated by specific blood and organ function tests and willing to use effective birth control.

What is being tested?

The study is testing the combination of TGR-1202, a PI3K delta inhibitor, with ruxolitinib in patients with myeloproliferative neoplasms. It's an early-phase trial designed to evaluate safety and how well these drugs work together.

What are the potential side effects?

Potential side effects may include changes in liver enzymes, bilirubin levels indicating liver function issues, kidney function alterations measured by creatinine levels, as well as general symptoms such as fatigue. Specific side effects related to TGR-1202 or ruxolitinib will be monitored closely.

Eligibility Criteria

Inclusion Criteria

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

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I am able to care for myself and perform daily activities.

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My organ functions are within normal ranges according to recent tests.

Exclusion Criteria

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

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I haven't had any cancer except for skin, prostate, cervical, or DCIS in the last 2 years.

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I haven't had a stroke, heart attack, or severe heart rhythm problems in the last 6 months.

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I have had a recent stem cell transplant or have active graft-versus-host disease.

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I have not had recent major surgery, chemotherapy, or immunotherapy.

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I have a history of HIV or active hepatitis A, B, or C.

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I am currently on immunosuppressive therapy or have recently had radiotherapy.

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I have not taken any experimental drugs or specific inhibitors recently.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ </=12 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~</=12 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and </=12 months for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Safety of TGR1202 in combination with ruxolitinib

Secondary study objectives

Blood levels of TGR1202 in combination with ruxolitinib (Pharmacokinetics)

Overall response

Total symptom score (MPN-TSS)

Other study objectives

JAK2V617F allele burden

Awards & Highlights

No Placebo-Only Group

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: Escalation and expansionExperimental Treatment2 Interventions

TGR1202 and Ruxolitinib combination

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

TGR-1202

2015

Completed Phase 1

~270

ruxolitinib

2017

Completed Phase 3

~660

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Ruxolitinib, a JAK1/2 inhibitor, works by blocking the Janus kinase (JAK) pathway, which is often overactive in PV due to mutations like JAK2 V617F. This inhibition reduces the excessive production of blood cells, alleviating symptoms and reducing spleen size. TGR-1202, a PI3K delta inhibitor, targets the PI3K/AKT/mTOR pathway, which is involved in cell growth and survival. By inhibiting this pathway, TGR-1202 can help control abnormal cell proliferation. These mechanisms are crucial for PV patients as they address the underlying causes of the disease, helping to manage symptoms and prevent complications such as thrombosis and progression to myelofibrosis.