Recruiting PHASE1, PHASE2 Myelofibrosis

New treatment option for Myelofibrosis

Official title A Study of Oral Nuvisertib (TP-3654) in Patients With Myelofibrosis

ClinicalTrials.gov ID: NCT04176198

What this study is testing

What is Nusivertib?

Nusivertib is an investigational medicine, given as a pill taken by mouth, being studied as a potential treatment for myelofibrosis.

Also referred to as TP-3654.

Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.

What it's testing: This study is a Phase 1/2, multicenter, dose-escalation, open-label trial to assess safety, tolerability, pharmacokinetics and pharmacodynamics of nuvisertib (TP-3654) in patients with intermediate or high-risk primary or secondary MF.

Phase 2: a mid-size study of how well it works

A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.

Who can take part

Ages 18 and older

You may be able to join if

Patients must meet all of the following to be eligible: Nuvisertib (TP-3654) Monotherapy Arm:
Confirmed pathological diagnosis of primary myelofibrosis (PMF) or post-PV-MF/post-ET- MF and intermediate or high-risk primary or secondary MF
Previously treated with JAK inhibitor(s) and is intolerant, resistant, refractory or has lost response to the JAK inhibitor(s) or is ineligible to be...
Fulfill the following clinical laboratory parameters:
Platelet count ≥ 25 x 10\^9 /L, without assistance of growth factors or platelet transfusions

You likely can't join if

will be prohibited from participating in this study: Nuvisertib (TP-3654) Monotherapy Arm:
Received previous systemic antineoplastic therapy or any experimental therapy within 2 weeks or 5 half-lives, whichever is longer, prior to Cycle 1...
Major surgery within 4 weeks prior to Cycle 1 Day 1 and/or not recovered adequately from from surgery prior to first dose.
Splenic irradiation within 6 months prior to Screening or prior splenectomy.
Prior allogeneic stem cell transplant within the last 6 months.
Eligible for allogeneic bone marrow or stem cell transplantation.

See the full eligibility criteria

Who can join

Patients must meet all of the following to be eligible: Nuvisertib (TP-3654) Monotherapy Arm:
Confirmed pathological diagnosis of primary myelofibrosis (PMF) or post-PV-MF/post-ET- MF and intermediate or high-risk primary or secondary MF
Previously treated with JAK inhibitor(s) and is intolerant, resistant, refractory or has lost response to the JAK inhibitor(s) or is ineligible to be treated with JAK inhibitor
Fulfill the following clinical laboratory parameters:
Platelet count ≥ 25 x 10\^9 /L, without assistance of growth factors or platelet transfusions
ANC ≥ 1 x 10\^9/L without assistance of granulocyte growth factors
Peripheral blood blast count \< 5%
ECOG performance status ≤ 1
Life expectancy ≥ 6 months
Adequate renal function
Adequate hepatic function
Adequate coagulation function
Splenomegaly (spleen volume of ≥ 450 cm3 by MRI or CT scan) within 2 weeks prior to Cycle 1 Day 1.
Dose escalation: At least 2 symptoms measurable (score ≥ 1) using the MF-SAF
Dose expansion: At least 2 symptoms measurable with each score of ≥ 3 or a total average score of ≥ 10 per MFSAF Nuvisertib (TP-3654) + Ruxolitinib Arm:
Confirmed pathological diagnosis of PMF or post-PV-MF/post ET- MF and intermediate or high-risk primary or secondary MF
On ruxolitinib treatment for ≥ 6 months, and on a stable dose of ruxolitinib (5 to 25 mg BID) for ≥ 8 weeks prior to the first dose of nuvisertib, but has either lost response or had a suboptimal or plateau in response
Fulfills the following clinical laboratory parameters:
Platelet count ≥ 50 × 10\^9/L (without assistance of growth factors or platelet transfusions)
ANC ≥ 1 × 109/L without assistance of granulocyte growth factors
Peripheral blood blast count \< 5% at screening
Adequate renal function
Adequate hepatic function
Adequate coagulation function
Splenomegaly (spleen volume of ≥ 450 cm3 by MRI/CT scan) within 2 weeks prior to Cycle 1 Day 1
At least 2 symptoms measurable with each score ≥ 3 or a total average score of ≥ 10 per MFSAF v4.0
ECOG performance status ≤ 1
Life expectancy ≥ 6 months Nuvisertib (TP-3654) + Momelotinib Arm
Confirmed pathological diagnosis of PMF or post-PV-MF/post ET-MF and intermediate or high-risk primary or secondary MF
Previously treated with an approved JAK inhibitor (except momelotinib) for PMF or Post-PV/ET MF for ≥ 12 weeks, or ≥ 4 weeks if JAK inhibitor therapy was complicated by a transfusion requirement of ≥ 4 units of red...
Fulfills the following clinical laboratory parameters:
Anemic, defined as Hb \<10 g/dL or requiring RBC transfusion at baseline
Platelet count ≥ 50 × 109/L (without assistance of growth factors or platelet transfusions)
ANC ≥ 1 × 109/L without assistance of granulocyte growth factors
Peripheral blood blast count \< 5% at screening
Adequate renal function
Adequate hepatic function
Adequate coagulation function
Splenomegaly (spleen volume of ≥ 450 cm3 by MRI/CT scan) within 2 weeks prior to Cycle 1 Day 1
At least 2 symptoms measurable with each score of ≥ 3 or a total average score of ≥ 10 per MFSAF v4.0
ECOG performance status ≤ 1
Life expectancy ≥ 6 months Patients meeting any one of these

What rules you out

will be prohibited from participating in this study: Nuvisertib (TP-3654) Monotherapy Arm:
Received previous systemic antineoplastic therapy or any experimental therapy within 2 weeks or 5 half-lives, whichever is longer, prior to Cycle 1 Day 1. Hydroxyurea or anagrelide are allowed up to 24 hours prior to...
Major surgery within 4 weeks prior to Cycle 1 Day 1 and/or not recovered adequately from from surgery prior to first dose.
Splenic irradiation within 6 months prior to Screening or prior splenectomy.
Prior allogeneic stem cell transplant within the last 6 months.
Eligible for allogeneic bone marrow or stem cell transplantation.
Unresolved Grade ≥ 2 non-hematological toxicity related to prior treatment
History of symptomatic congestive heart failure, or myocardial infarction, or uncontrolled arrhythmia within 6 months prior to Cycle 1 Day 1; left ventricular ejection fraction (LVEF) \< 45% by echocardiogram within 4...
Corrected QT interval \> 480msec.
Prior or concurrent malignancy that could interfere with the investigational regime.
Known history of chronic liver disease, e.g. portal hypertension or any of its complications, cirrhosis, Child-Pugh C, auto-immune hepatitis, alpha-1 anti-trypsin deficiency, Wilson's disease, etc.
Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic antimicrobial within 1 week prior to Cycle 1 Day 1.
Chronic active or acute viral hepatitis A, B, or C infection (testing for hepatitis B and C are required)
Exhibited allergic reactions or sensitivity to nuvisertib, or similar compound.
Medical condition or GI tract surgery that could impair absorption or result in short bowel syndrome with diarrhea.
Systemic steroid therapy (\>10 mg daily prednisone or equivalent) within 1 week prior to the first dose of study treatment (note: topical, inhaled, nasal, and ophthalmic steroids are not prohibited).
Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or thalassemia, or severe GI bleeding.
Pregnant or breastfeeding
Currently receiving any other investigational agent. Nuvisertib (TP-3654) + Ruxolitinib Arm:
Received previous systemic antineoplastic therapy (other than ruxolitinib) or any other experimental therapy within 2 weeks or 5 half-lives, whichever is longer, prior to Cycle 1 Day 1 (Note: Prior treatment with...
Received systemic steroid therapy (\>10 mg daily prednisone or equivalent) within 1 week prior to Cycle 1 Day 1 (Note: Topical, inhaled, nasal, and ophthalmic steroids are not prohibited)
Known allergic reactions or sensitivity to nuvisertib, or similar compound.
Splenic irradiation within 6 months prior to Screening or prior splenectomy
Prior allogeneic stem cell transplant within the last 6 months (Note: Patients who have relapsed after 6 months post-transplant and do not have active GVHD are eligible).
Eligible for allogeneic bone marrow or stem cell transplantation (Note: Patients who are not willing to undergo transplantation or for whom a suitable donor is not available are considered as transplant ineligible.)
Major surgery within 4 weeks prior to Cycle 1 Day 1 and/or have not recovered adequately prior to first dose.
Active, uncontrolled bacterial, viral, or fungal infections, requiring parenteral antimicrobial within 1 week prior to Cycle 1 Day 1
Chronic active or acute viral hepatitis A, B, or C infection (testing for hepatitis B and C are required)
Known history of chronic liver disease (eg, portal hypertension or any of its complications, cirrhosis, Child-Pugh C, auto-immune hepatitis, alpha-1 anti-trypsin deficiency, Wilson's disease, etc) (Note: Abnormal liver...
Unresolved Grade ≥ 2 non-hematological adverse events related to prior treatment (stable Grade 2 conditions may be permitted in consultation with the Sponsor)
History of myocardial infarction or symptomatic congestive heart failure or uncontrolled arrhythmia within 6 months prior to Cycle 1 Day 1; LVEF \<45% by echocardiogram within 4 weeks prior to Cycle 1 Day 1
Corrected QTcF of \> 480 msec
Prior or concurrent malignancy that could interfere with the safety or how well it works assessment of the study intervention
History of a medical condition or GI tract surgery that could impair absorption or could result in short bowel syndrome with diarrhea
Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or thalassemia, or severe GI bleeding
Pregnant or breastfeeding Nuvisertib (TP-3654) + Momelotinib Arm:
Received previous systemic antineoplastic therapy or any experimental therapy within 2 weeks or 5 half-lives, whichever is longer, prior to Cycle 1 Day 1 (Notes: Prior treatment with momelotinib or nuvisertib is not...
Received systemic steroid therapy (\>10 mg daily prednisone or equivalent) within 1 week prior to Cycle 1 Day 1 (Note: Topical, inhaled, nasal, and ophthalmic steroids are not prohibited).
Known allergic reactions or sensitivity to nuvisertib, momelotinib, or any structurally similar drug, or to any component of the formulations of either study intervention
Splenic irradiation within 6 months prior to screening or prior splenectomy
Prior allogenic stem cell transplant within the last 6 months (Note: Patients who have relapsed after 6 months post-transplant and do not have active GVHD are eligible).
Eligible for allogeneic bone marrow or stem cell transplantation (Note: Patients who are not willing to undergo transplantation or for whom a suitable donor is not available are considered as transplant ineligible).
Major surgery within 4 weeks prior to Cycle 1 Day 1 and/or have not recovered adequately from surgery prior to first dose.
Active, uncontrolled bacterial, viral, or fungal infections, requiring parenteral antimicrobial within 1 week prior to Cycle 1 Day 1
Chronic active or acute viral hepatitis A, B, or C infection (testing for hepatitis B and C are required)
Known history of chronic liver disease (eg, portal hypertension or any of its complications, cirrhosis, Child-Pugh C, auto-immune hepatitis, alpha-1 anti-trypsin deficiency, Wilson's disease, etc) (Note: Abnormal liver...
Unresolved Grade ≥ 2 non-hematological adverse events related to prior treatment (stable Grade 2 conditions may be permitted in consultation with the Sponsor)
Presence of Grade ≥ 2 peripheral neuropathy
History of myocardial infarction or symptomatic congestive heart failure or uncontrolled arrhythmia within 6 months prior to Cycle 1 Day 1; LVEF \< 45% by echocardiogram within 4 weeks prior to Cycle 1 Day 1
Corrected QTcF of \> 480 msec
Prior or concurrent malignancy that could interfere with the safety or how well it works assessment of the study intervention
History of a medical condition or GI tract surgery that could impair absorption or could result in short bowel syndrome with diarrhea
Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or thalassemia, or severe GI bleeding
Pregnant or breastfeeding

The study team makes the final eligibility decision.

Where it's taking place

Birmingham, Alabama, United States
Tucson, Arizona, United States
Duarte, California, United States
Los Angeles, California, United States
Newport Beach, California, United States
Denver, Colorado, United States
New Haven, Connecticut, United States
Gainesville, Florida, United States
Miami, Florida, United States
Atlanta, Georgia, United States
Chicago, Illinois, United States
Baltimore, Maryland, United States
Boston, Massachusetts, United States
Ann Arbor, Michigan, United States
Minneapolis, Minnesota, United States
St Louis, Missouri, United States
Hackensack, New Jersey, United States
Buffalo, New York, United States
New York, New York, United States
The Bronx, New York, United States

+ 55 more site(s).

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include Birmingham, Alabama, United States; Tucson, Arizona, United States; Duarte, California, United States; Los Angeles, California, United States; Newport Beach, California, United States; Denver, Colorado, United States and 69 more location(s). Enter your location above to see the nearest site and check your eligibility.

Explore other conditions

Obesity Type 2 diabetes Type 1 diabetes Prediabetes Weight loss Metabolic syndrome High cholesterol High triglycerides High blood pressure PCOS Hypothyroidism Thyroid disease Gout Fatty liver disease (NAFLD/NASH)Heart failure Coronary artery disease

BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.