Health TrialsbyHealthPanel

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

ConditionMyelofibrosis
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorSumitomo Pharma America, Inc.

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

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

Disqualifiers

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 Cycle 1 Day 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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Nusivertib

    Drug

    Oral PIM Inhibitor

  • Ruxolitinib

    Drug

    Oral JAK inhibitor

  • Momelotinib

    Drug

    Oral JAK inhibitor

Treatment groups

240 Participants
are divided into 3 treatment groups
Group A: Arm 1: nuvisertib (TP-3654)Experimental treatment 1 intervention
Group B: Arm 2: nuvisertib (TP-3654) added on to ruxolitinibExperimental treatment 2 interventions
Group C: Arm 3: nuvisertib (TP-3654) in combination with momelotinibExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Determine the incidence of dose-limiting toxicities (DLTs)

Number of participants with DLTs

Time frame
28 days
2

Determine the incidence of treatment emergent adverse events

Number of participants with Treatment Emergent Adverse Events and Serious Adverse Events

Time frame
From start of treatment to end of study
3

Assess patients for any evidence of preliminary activity by determining the number of patients with ≥ 35% spleen volume reduction (SVR35)

Number of participants with ≥ 35% spleen volume reduction (SVR35)

Time frame
From start of treatment to end of study

Secondary outcomes

1

Number of participants achieving objective response by IWG-MRT response criteria

Number of participants achieving complete remission, partial remission, clinical improvement, progressive disease and stable disease.

Time frame
From start of treatment to end of study
2

Number of participants who have ≥ 25% spleen volume reduction

Number of participants who have ≥ 25% spleen volume reduction compared to baseline

Time frame
Every 12 weeks from cycle 1 day 1 through cycle 19 day 1, and then every 24 weeks therafter during treatment.
3

Number of participants with ≥ 50% improvement in total symptom score (TSS50) at week 24

Number of participants who have ≥ 50% total symptom score reduction by MFSAF compared to baseline after 24 weeks of treatment.

Time frame
24 weeks
4

Determine the change in Patient Global Impression of Change (PGIC) at week 24 through end of study.

Change in PGIC score

Time frame
After 24 weeks of treatment to end of study

Other outcomes

1

Number of patients with reduction in bone marrow fibrosis

Time frame
Every 24 weeks to end of study
2

Study potential pharmacodynamic (PD) markers of nuvisertib

Evaluate exploratory biomarkers, including change in protein phosphorylation and inflammatory cytokines, in peripheral blood samples and bone marrow biopsy samples.

Time frame
12 months
3

Nuvisertib monotherapy: Changes in platelet count over time in patients with baseline platelet count < 100 x 10^9/L

Time frame
From start of treatment to end of study
4

Nuvisertib combination arms: Assess the increase in hemoglobin ≥1.5 or ≥ 2 g/dL from baseline

Time frame
From start of treatment to end of study

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Sumitomo Pharma America, Inc.

Lead sponsor

Source ClinicalTrials.gov
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