Myelofibrosis Clinical Trial
Official title:
A Phase 1b/2 Study of BMS-986158 Monotherapy and in Combination With Either Ruxolitinib or Fedratinib in Participants With DIPSS-Intermediate or High Risk Myelofibrosis
| Verified date | May 2024 |
| Source | Bristol-Myers Squibb |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
The purpose of this study is to assess the safety, tolerability, and efficacy of BMS-986158 alone and in combination with either Ruxolitinib or Fedratinib in participants with Dynamic International Prognostic Scoring System (DIPSS)-intermediate or high risk blood cancer. Part 1 consists of BMS-986158 in combination with either Ruxolitinib or Fedratinib and Part 2 consists of BMS-986158 in combination with either Ruxolitinib or Fedratinib and BMS-986158 alone.
| Status | Active, not recruiting |
| Enrollment | 216 |
| Est. completion date | May 31, 2026 |
| Est. primary completion date | May 31, 2026 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | Inclusion Criteria: - Diagnosis of primary myelofibrosis (PMF), post-essential thrombocythemia (ET) or post-polycythemia vera (PV) myelofibrosis - Treatment-related toxicities from prior therapy resolved to Grade 1 or pre-treatment baseline or determined to be irreversible prior to study treatment - Must agree to follow specific methods of contraception, if applicable Exclusion Criteria: - Women who are pregnant or breastfeeding at screening - Any significant acute or uncontrolled chronic medical illness Other protocol-defined inclusion/exclusion criteria apply |
| Country | Name | City | State |
|---|---|---|---|
| Australia | Local Institution - 0036 | Blacktown | New South Wales |
| Australia | Local Institution - 0007 | East Melbourne | Victoria |
| Australia | Local Institution - 0006 | Heidelberg | Victoria |
| Australia | Local Institution - 0041 | Nedlands | Western Australia |
| Australia | Local Institution - 0015 | West Perth | Western Australia |
| Australia | Local Institution - 0032 | Wollongong | New South Wales |
| France | Local Institution - 0030 | Brest | |
| France | Local Institution - 0008 | Marseille | |
| France | Local Institution - 0027 | Nice | |
| France | Local Institution - 0011 | Paris | |
| France | Local Institution - 0010 | Villejuif | |
| Germany | Local Institution - 0040 | Chemnitz | Sachsen |
| Germany | Local Institution - 0068 | Erding | |
| Germany | Local Institution - 0039 | Essen | Nordrhein-Westfalen |
| Germany | Local Institution - 0035 | Halle | Sachsen-Anhalt |
| Germany | Local Institution - 0050 | Lübeck | Schleswig-Holstein |
| Greece | Local Institution - 0061 | Chaidari | Attikí |
| Greece | Local Institution - 0047 | Thessaloniki | Thessaloníki |
| Hungary | Local Institution - 0075 | Budapest | |
| Hungary | Local Institution - 0074 | Debrecen | |
| Hungary | Local Institution - 0072 | Nyiregyhaza | Szabolcs-Szatmár-Bereg |
| Hungary | Local Institution - 0073 | Szeged | Csongrád |
| Israel | Local Institution - 0086 | Be'er Sheva | HaDarom |
| Israel | Local Institution - 0016 | Jerusalem | |
| Israel | Local Institution - 0018 | Petah-Tikva | |
| Israel | Local Institution - 0017 | Ramat Gan | |
| Israel | Local Institution - 0019 | Tel Aviv | |
| Italy | Local Institution - 0003 | Bologna | |
| Italy | Local Institution - 0002 | Brescia | |
| Italy | Local Institution - 0001 | Firenze | |
| Italy | Local Institution - 0012 | Verona | |
| Korea, Republic of | Local Institution - 0049 | Seongnam | Kyonggi-do |
| Korea, Republic of | Local Institution - 0048 | Seoul | Seoul-teukbyeolsi [Seoul] |
| Korea, Republic of | Local Institution - 0053 | Seoul | Seoul-teukbyeolsi [Seoul] |
| Poland | Local Institution - 0062 | Gdansk | |
| Poland | Local Institution - 0077 | Slupsk | Pomorskie |
| Romania | Local Institution - 0052 | Bucuresti | Cluj |
| Romania | Local Institution - 0083 | Bucuresti | |
| Romania | Local Institution - 0051 | Cluj | |
| Spain | Local Institution - 0020 | Badalona | Barcelona [Barcelona] |
| Spain | Local Institution - 0026 | Madrid | |
| Spain | Local Institution - 0054 | Madrid | Madrid, Comunidad De |
| Spain | Local Institution - 0021 | Salamanca | |
| Spain | Local Institution - 0029 | Santander | |
| Spain | Local Institution - 0094 | València | |
| United States | Local Institution - 0033 | Ann Arbor | Michigan |
| United States | Local Institution - 0076 | Chapel Hill | North Carolina |
| United States | Local Institution - 0045 | Hackensack | New Jersey |
| United States | Local Institution - 0090 | Lake Mary | Florida |
| United States | Local Institution - 0043 | New Orleans | Louisiana |
| United States | Local Institution - 0069 | Newport Beach | California |
| United States | Local Institution - 0042 | Pittsburgh | Pennsylvania |
| United States | Local Institution - 0038 | Worcester | Massachusetts |
| Lead Sponsor | Collaborator |
|---|---|
| Bristol-Myers Squibb |
United States, Australia, France, Germany, Greece, Hungary, Israel, Italy, Korea, Republic of, Poland, Romania, Spain,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Incidence of adverse events (AEs) | Up to 52 months | ||
| Primary | Incidence of serious adverse events (SAEs) | Up to 52 months | ||
| Primary | Incidence of AEs meeting protocol-defined dose-limiting toxicity (DLT) criteria | Up to 26 months | ||
| Primary | Incidence of AEs leading to discontinuation | Up to 52 months | ||
| Primary | Incidence of death | Up to 52 months | ||
| Secondary | Spleen volume reduction (SVR) at end of Cycle 6 assessed by Blinded Independent Central Review (BICR) | Up to 175 days | ||
| Secondary | Response rate defined as proportion of participants with SVR = 35% by MRI (preferred) or CT (if MRI is contraindicated and if CT is allowed by local guidelines) assessed by BICR | Up to 175 days | ||
| Secondary | SVR at end of Cycle 3 and 6 assessed by BICR | Up to 175 days | ||
| Secondary | Response rate defined as proportion of participants with SVR = 25% by MRI (preferred) or CT (if MRI is contraindicated and if CT is allowed by local guidelines) assessed by BICR | Up to 175 days | ||
| Secondary | Symptom response rate (SRR) based on total symptom score (TSS) measured by Myelofibrosis Symptom Assessment Form (MFSAF) | Up to 175 days | ||
| Secondary | Additional measures based on TSS measured by MFSAF | Up to 175 days | ||
| Secondary | For transfusion independent (TI), proportion of participants having = 2.0 g/dL hemoglobin (Hgb) increase over baseline | Up to 24 months | ||
| Secondary | For transfusion dependent (TD), proportion of participants becoming TI as measured by the absence of red blood cell (RBC) transfusions over any consecutive 12-week period | Up to 24 months | ||
| Secondary | For transfusion dependent (TD), proportion of participants becoming Tl as measured by the absence of erythropoiesis stimulating agents (ESA) over any consecutive 12-week period | Up to 24 months | ||
| Secondary | For transfusion dependent (TD), proportion of participants becoming Tl as measured by the absence of hydroxyurea over any consecutive 12-week period | Up to 24 months | ||
| Secondary | Summary of plasma concentrations pharmacokinetics (PK) parameters: maximum observed concentration (Cmax) | Up to 56 days | ||
| Secondary | Summary of plasma concentrations PK parameters: time of maximum observed concentration (Tmax) | Up to 56 days | ||
| Secondary | Summary of plasma concentrations PK parameters: area under the concentration-time curve from time zero to the time of the last quantifiable concentration ((AUC (0-T)) | Up to 56 days | ||
| Secondary | Time from Dose 1, Day 1 to death due to any reason or disease progression (per modified IWG-MRT 2013) assessed by BICR: SDPFS rates at 6 months and 12 months | International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) Spleen and disease progression free survival (SDPFS) |
6 month and 12 month | |
| Secondary | Time from Dose 1, Day 1 to death due to any reason or disease progression (per modified IWG-MRT 2013) assessed by BICR: median SDPFS at 6 months and 12 months | 6 month and 12 month |
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