Leukemia Clinical Trial
Official title:
A Phase 1/2 Study of CPI-0610, a Small Molecule Inhibitor of BET Proteins: Phase 1 (Dose Escalation of CPI-0610 in Patients With Hematological Malignancies) and Phase 2 (Dose Expansion of CPI-0610 With and Without Ruxolitinib in Patients With Myelofibrosis and Essential Thrombocytopenia)
Verified date | March 2024 |
Source | Constellation Pharmaceuticals |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Phase 1 Part (Complete): Open-label, sequential dose escalation study of pelabresib in patients with previously treated Acute Leukemia, Myelodysplastic Syndrome, Myelodysplastic/Myeloproliferative Neoplasms, and Myelofibrosis. Phase 2 Part: Open-label study of CPI-0610 with and without Ruxolitinib in patients with Myelofibrosis. CPI-0610 is a small molecule inhibitor of bromodomain and extra-terminal (BET) proteins.
Status | Active, not recruiting |
Enrollment | 336 |
Est. completion date | October 31, 2024 |
Est. primary completion date | October 31, 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: Phase 2 part: Patients with confirmed diagnosis of MF who meet all of the following criteria: - ANC = 1 x 10^9/L without the assistance of granulocyte growth factors - Peripheral blood blast count <10% - ECOG performance status = 2. - Adequate hematological, renal, hepatic, and coagulation laboratory assessments - No prior treatment with a BET inhibitor - Patients must give written informed consent to participate in this study before the performance of any study-related procedure. For Arm 1 and 2 the following criteria should be considered: - Patients with confirmed diagnosis of MF who meet all of the following criteria - Dynamic International Prognostic Scoring System (DIPSS) risk category of intermediate-2 or higher - Spleen volume = 450 cm^3 by MRI or CT for Cohorts 1B and 2B OR RBC transfusion dependent (defined as an average of =2 units of RBC transfusions per month (total of greater than 6 RBC transfusions) over the 12 weeks prior to enrollment for Cohorts 1A and 2A) - At least 2 symptoms measurable (Score = 1) using the Myelofibrosis Symptom Assessment Form Version 4.0 (MFSAF v4.0) - Platelet count = 75 x 10^9/L without the assistance of thrombopoietic factors or transfusions for at least 14 days - Arm (Arm 1): Previously treated with a JAK inhibitor and be intolerant, resistant, refractory, or lost response to the JAK inhibitor; have not received the JAK inhibitor within 2 weeks prior to the start of study drug, or are ineligible to be treated with a JAK inhibitor - Combination Arm (Arm 2): Must have received single agent ruxolitinib and be on a stable dose for a minimum 8 weeks but have disease that is not being adequately controlled by ruxolitinib For Arm 3 (JAK inhibitors naïve) the following criteria should be considered: - Patients with confirmed diagnosis of MF who meet all of the following criteria - Dynamic International Prognostic Scoring System (DIPSS) risk category of intermediate-2 or higher - Platelet count = 100 x 10^9/L without the assistance of thrombopoietic factors or transfusions - Spleen volume = 450 cm^3 by MRI/CT - At least 2 symptoms measurable (Score = 3) or a total score of = 10 using the Myelofibrosis Symptom Assessment Form Version 4.0 ( MFSAF v4.0) - No prior treatment with JAKi allowed For Arm 4 (ET Expansion) the following criteria should be considered: - Patients with a confirmed diagnosis of ET - High-risk disease, defined as meeting at least one of the following criteria: - Age > 60 years - Platelet count > 1500 × 10^9/L (at any point during the patient's disease) - Previously documented thrombosis, erythromelalgia, or migraine - Previous hemorrhage related to ET - Diabetes or hypertension requiring pharmacological therapy for > 6 months - Have =2 symptoms with an average score = 3 over the 7-day period prior to Cycle 1 Day 1 or an average total score of =15 over the 7-day period prior to Cycle 1 Day 1 using the using the MPN SAF - Platelets > 600 × 10^9/L - Resistant or intolerant to HU Exclusion Criteria: - Current known active or chronic infection with human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C. - Impaired cardiac function or clinically significant cardiac diseases - Patients with Child-Pugh Class B or C - Impairment of gastrointestinal (GI) function or GI disease that could significantly alter the absorption of pelabresib and/or ruxolitinib, including any unresolved nausea, vomiting, or diarrhea that is CTCAE Grade >1 - Prior treatment with a BET inhibitor. - Pregnant or lactating women - Any other concurrent severe and/or uncontrolled concomitant medical condition that could compromise participation in the study - Patients unwilling or unable to comply with this study protocol. |
Country | Name | City | State |
---|---|---|---|
Belgium | ZNA Stuyvenberg Antwerpen | Antwerpen | |
Belgium | AZ Sint-Jan Burgge-Oostende AV- Campus Sint-Jan | Brugge | West-Vlaanderen |
Belgium | UZ Leuven - Campus Gasthuisberg | Leuven | Viaams Braban |
Canada | University of Alberta Hospital | Edmonton | Alberta |
Canada | Juravinski Cancer Centre | Hamilton | Ontario |
Canada | Jewish General Hospital | Montreal | Quebec |
Canada | Princess Margaret Cancer Centre | Toronto | Ontario |
Canada | St. Paul's Hospital | Vancouver | British Columbia |
France | CHRU de Lille - Hopital Claude Huriez - Maladies du Sang | Lille | Nord-Pas-de-Calais |
France | Institut de cancérologie du Gard - Hematologie clinique | Nîmes | Gard |
France | CHU - Hopital Saint Louis - Centre D'Investigations Clinique | Paris | |
France | CHRU de Lille - Hopital Claude Huriez | Toulouse | Haute-Garonne |
France | Institut Gustave Roussy | Villejuif | Ile-de-France |
Germany | Universitätsklinikum Bonn | Bonn | Nordrhein-Westfalen |
Germany | Universitätsklinikum Leipzig AöR | Leipzig | Sachsen |
Italy | Institue of Hematology "L. and A. Seràgnoli" | Bologna | Emilia-Romagna |
Italy | Azienda Ospedaliero-Universitaria Careggi | Firenze | |
Italy | AOU S.Martino, IRCCS, IST-Istituto Nazionale Ricerca Sul Can | Genova | Liguria |
Italy | Ospedale Maggiore Policlinico, Fondazione IRCCS Ca' Granda | Milano | Lombardia |
Italy | AOU Maggiore della Carità | Novara | |
Italy | IRCCS Policlinico San Matteo, Università degli studi di Pavi | Pavia | Lombardia |
Italy | Servizio Sanitario Regionale Emilia-Romagna - Azienda Unita Sanitaria Locale (AUSL) di Rimini - Ospedale Infermi di Rimini | Rimini | Emilia-Romagna |
Italy | Ospedale di Circolo, PO Varese, AO Ospedale di Circolo e Fon | Varese | Lombardia |
Netherlands | VUmcResearch B.V. | Amsterdam | Noord-Holland |
Netherlands | Maastricht University Medical Center | Maastricht | Limburg |
Netherlands | Erasmus Universitair Medisch Centrum Rotterdam | Rotterdam | Zuid-Holland |
Poland | Uniwersyteckie Centrum Kliniczne | Gdansk | Pomorskie |
Poland | Instytut Hematologii i Transfuzjologii w Warszawie | Warszawa | Mazowieckie |
United Kingdom | Belfast City Hospital | Belfast | |
United Kingdom | University of Cambridge | Cambridge | |
United Kingdom | University Hospital of Wales | Cardiff | |
United Kingdom | Beatson West of Scotland Cancer Centre | Glasgow | |
United Kingdom | Oxford University Hospitals | Headington | Oxford |
United Kingdom | Guys and St Thomas' Hospital - Haematology | London | |
United Kingdom | University College London Hospital's NHS foundation Trust | London | |
United Kingdom | The Christie Hospital | Manchester | |
United States | University of Michigan Medical Center | Ann Arbor | Michigan |
United States | Massachusetts General Hospital Cancer Center | Boston | Massachusetts |
United States | Northwestern University - Lurie Comprehensive Cancer Center | Chicago | Illinois |
United States | The University of Texas MD Anderson Cancer Center | Houston | Texas |
United States | Mayo Clinic Jacksonville | Jacksonville | Florida |
United States | UCLA Medical Center | Los Angeles | California |
United States | Froedtert & Medical College of Wisconsin | Milwaukee | Wisconsin |
United States | ICAHN School of Medicine at Mount Sinai | New York | New York |
United States | Memorial Sloan Kettering Cancer Center | New York | New York |
United States | Weill Medical College and New York Presbyterian Hospital | New York | New York |
United States | Mayo Clinic Arizona | Phoenix | Arizona |
United States | Washington University School of Medicne Neuromuscular Division Department of Neurology Research | Saint Louis | Missouri |
Lead Sponsor | Collaborator |
---|---|
Constellation Pharmaceuticals | The Leukemia and Lymphoma Society |
United States, Belgium, Canada, France, Germany, Italy, Netherlands, Poland, United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Phase 2 (Arms 1, 2, and 3): Evaluate response category rate | Rate of response by the International Working Group - Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria after 24 weeks | ||
Other | Phase 2 (Arms 1, 2, and 3): Evaluate the rate of RBC transfusion and the RBC transfusion dependence rate | Average number of RBC units per subject-month, up to 24 weeks and beyond | ||
Primary | Phase 2 (Cohorts 1B and 2B and Arm 3): Evaluate the spleenic response | By imaging after 24 weeks | ||
Primary | Phase 2 (Cohorts 1A and 2A): Evaluate the RBC (Red Blood Cell) transfusion independence rate | Absence of RBC transfusion and no hemoglobin level below 8 g/dL in the prior 12 weeks | ||
Primary | Phase 2 (Arm 4): Evaluate the complete hematological response rate | 1 cycle (21 days) | ||
Secondary | Phase 2 (Arms 1, 2, and 3): Evaluate the duration of the spleenic response by imaging | Through study completion or end of treatment, up to 24 weeks and beyond | ||
Secondary | Phase 2 (all arms): Evaluate the change in patient reported outcomes | Changes from baseline in the total symptom score (MFSAF v4.0) and PGIC after 24 weeks | ||
Secondary | Phase 2 (all arms): area under the curve (AUC) | Assessed during Cycle 1 (first 21 days on study) | ||
Secondary | Phase 2 (all arms): maximum observed plasma concentration (Cmax) | Assessed during Cycle 1 (first 21 days on study) |
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