A Phase 1/2 Study of CPI-0610 With and Without Ruxolitinib in Patients With Hematologic and Myeloproliferative Malignancies
NCT ID: NCT02158858
Last Updated: 2025-10-08
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE1/PHASE2
336 participants
INTERVENTIONAL
2014-07-16
2025-01-09
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Pelabresib (CPI-0610) is a small molecule inhibitor of bromodomain and extra-terminal (BET) proteins.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Phase 3 Study of Pelabresib (CPI-0610) in Myelofibrosis (MF) (MANIFEST-2)
NCT04603495
Study of Oral Navitoclax Tablet In Combination With Oral Ruxolitinib Tablet When Compared With Oral Ruxolitinib Tablet To Assess Change In Spleen Volume In Adult Participants With Myelofibrosis
NCT04472598
Phase III Study Investigating the Efficacy and Safety of Ruxolitinib in Early Myelofibrosis Patients With High Molecular Risk Mutations.
NCT02598297
A Study Comparing Siltuximab Plus Best Supportive Care to Placebo Plus Best Supportive Care in Anemic Patients With International Prognostic Scoring System Low- or Intermediate-1-Risk Myelodysplastic Syndrome
NCT01513317
Study of AMD3100 (Plerixafor) and Rituximab in Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
NCT00694590
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Phase 1
Patients are enrolled in sequential cohorts (acute leukemia, including acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), and acute undifferentiated or biphenotypic leukemia; chronic myelogenous leukemia (CML) in blast crisis; myelodysplastic syndrome (MDS); myelodysplastic/myeloproliferative neoplasms (MDS/MPN); or myelofibrosis (MF)) and receive escalating doses of pelabresib (CPI-0610).
Pelabresib
CPI-0610 is administered orally once daily for 14 consecutive days, followed by a 7-day break (1 cycle = 21 days)
Phase 2 (Arm 1): Prior JAKi Monotherapy Arm (MF patients treated with pelabresib alone)
* Cohort 1A: Open to patients with MF who are Transfusion Dependent (TD) and who have previously been treated with a JAKi and are intolerant, resistant, refractory or lost response to the JAKi, or are ineligible to be treated with a JAKi (pelabresib (CPI-0610) alone)
* Cohort 1B: Open to patients with MF who are not TD and who have previously been treated with a JAKi and are intolerant, resistant, refractory or lost response to the JAKi, or are ineligible to be treated with a JAKi. (pelabresib (CPI-0610) alone)
Pelabresib
CPI-0610 is administered orally once daily for 14 consecutive days, followed by a 7-day break (1 cycle = 21 days)
Phase 2 (Arm 2): Prior JAKi Combination Arm
* Cohort 2A: Open to patients with MF who are Transfusion Dependent (TD) and are currently taking ruxolitinib but have disease that is not being adequately controlled by ruxolitinib (pelabresib (CPI-0610) + Ruxolitinib)
* Cohort 2B: Open to patients with MF who are not TD and are currently taking ruxolitinib but have disease that is not being adequately controlled by ruxolitinib. (pelabresib (CPI-0610) + Ruxolitinib)
Pelabresib
CPI-0610 is administered orally once daily for 14 consecutive days, followed by a 7-day break (1 cycle = 21 days)
Ruxolitinib
Ruxolitinib is given orally, twice daily (BID), on a continuous basis for 21 consecutive days of each 21-day cycle.
Phase 2 (Arm 3): JAKi Naïve Combination Arm
Open to patients with MF who have not previously received a JAKi (pelabresib (CPI-0610) + Ruxolitinib)
Pelabresib
CPI-0610 is administered orally once daily for 14 consecutive days, followed by a 7-day break (1 cycle = 21 days)
Ruxolitinib
Ruxolitinib is given orally, twice daily (BID), on a continuous basis for 21 consecutive days of each 21-day cycle.
Phase 2 (Arm 4): Essential Thrombocythemia (ET) Monotherapy Arm
Open to high-risk patients with ET who are resistant or intolerant to hydroxyurea (HU) (pelabresib (CPI-0610) alone)
Pelabresib
CPI-0610 is administered orally once daily for 14 consecutive days, followed by a 7-day break (1 cycle = 21 days)
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Pelabresib
CPI-0610 is administered orally once daily for 14 consecutive days, followed by a 7-day break (1 cycle = 21 days)
Ruxolitinib
Ruxolitinib is given orally, twice daily (BID), on a continuous basis for 21 consecutive days of each 21-day cycle.
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Diagnosis: Histologically or cytologically confirmed diagnosis of one of the following hematologic malignancies:
* Acute myelogenous leukemia (AML)
* Acute lymphocytic leukemia (ALL)
* Acute undifferentiated or biphenotypic leukemia
* Chronic myeloid leukemia (CML) in blast crisis
* Myelodysplastic syndrome (MDS)
* Myelodysplastic/myeloproliferative neoplasms (MDS/MPN)
* Myelofibrosis (MF)
* Performance Status: ECOG ≤2.
* Organ Function:
* Serum total bilirubin ≤1.5 × ULN
* AST/ALT ≤2.5 × ULN (up to 5 × ULN if due to leukemic infiltration)
* Serum creatinine ≤2.0 × ULN or CrCl ≥30 mL/min
* Hematology (MF only):
* Platelet count ≥50 × 10⁹/L and ANC ≥1 × 10⁹/L (MF not on ruxolitinib)
* Platelet count ≥75 × 10⁹/L and ANC ≥1 × 10⁹/L (MF on ruxolitinib)
* Other:
* DIPSS-plus risk category of intermediate-2 or high (MF only)
* Serum glucose ≤160 mg/dL (or HbA1C ≤7%)
* Fully recovered from major surgery and acute toxic effects of prior therapy
* Negative pregnancy test for women of childbearing potential
* Agreement to use appropriate contraception
* Written informed consent
1. MF Arms (Prior JAKi, Add-on JAKi, JAKi Naïve)
* Age: Adults ≥18 years
* Diagnosis: Confirmed primary MF or MF evolved from ET or PV
* Risk: DIPSS intermediate-2 or higher
* Platelets:
* ≥75 × 10⁹/L (Arms 1 \& 2)
* ≥100 × 10⁹/L (Arm 3, JAKi naïve)
* ANC: ≥1 × 10⁹/L
* Spleen Volume: ≥450 cm³ by MRI/CT (non-TD cohorts) OR
* Transfusion Dependence: Average ≥2 RBC transfusions/month (total ≥6 in prior 12 weeks) for TD cohorts
* Peripheral Blood Blasts: \<10%
* Symptoms: At least 2 symptoms measurable (score ≥1 for Arms 1 \& 2; score ≥3 or total ≥10 for Arm 3) using MFSAF v4.0
* Treatment History:
* Arm 1 (Prior JAKi): Previously treated with JAKi and intolerant, resistant, refractory, or lost response, or ineligible for JAKi
* Arm 2 (Add-on JAKi): On ruxolitinib ≥6 months, stable dose ≥8 weeks, not adequately controlled
* Arm 3 (JAKi Naïve): No prior JAKi, eligible for ruxolitinib
* Performance Status: ECOG ≤2
* Organ Function: Serum direct bilirubin \<2 × ULN, AST/ALT ≤2.5 × ULN (up to 5 × ULN if due to liver involvement), CrCl ≥45 mL/min
* Other: Fully recovered from major surgery/acute toxic effects, effective contraception, written informed consent
2. ET Arm (High-Risk ET)
* Age: Adults ≥18 years
* Diagnosis: Confirmed ET (WHO 2016 criteria)
* High-Risk: At least one of:
* Age \>60 years
* Platelets \>1500 × 10⁹/L
* Prior thrombosis, erythromelalgia, or migraine (disease-related)
* Prior hemorrhage related to ET
* Diabetes/hypertension requiring therapy \>6 months
* Symptoms: ≥2 symptoms with average score ≥3 or total score ≥15 (MPN-SAF)
* Platelets: \>600 × 10⁹/L
* Resistant/Intolerant to HU: As defined by ELN
* Performance Status: ECOG ≤2
* Life Expectancy: \>24 weeks
* ANC: ≥1 × 10⁹/L
* Organ Function: Serum direct bilirubin \<2 × ULN, AST/ALT ≤2.5 × ULN, CrCl ≥45 mL/min
* Other: Fully recovered from major surgery/acute toxic effects, effective contraception, written informed consent
Exclusion Criteria
* Relapsed/refractory acute leukemia where further induction chemotherapy is beneficial
* Acute leukemia relapse \<6 months after allogeneic SCT
* CML in blast crisis treated with only one TKI
* Very low/low risk MDS without prior treatment
* CNS involvement by leukemia (unless resolved)
* Active HIV, Hepatitis B or C infection
* GI impairment affecting absorption (unresolved nausea, vomiting, diarrhea \>CTCAE grade 1)
* Significant cardiac disease (recent MI/angina, high cTn, QTcF \>470 ms, LVEF \<50%, uncontrolled arrhythmia, etc.)
* Severe/uncontrolled comorbidities
* Recent systemic anti-cancer therapy (other than hydroxyurea/radiotherapy) \<2 weeks prior
* Ongoing or recent JAK inhibitor use (\<2 weeks prior, MF only)
* Recent therapeutic antibody (\<4 weeks) or investigational agent (\<2 weeks or \<5 half-lives)
* Use of strong CYP450 inhibitors/inducers or drugs with Torsades de Pointes risk
* Immunosuppressive treatment that cannot be discontinued
* Pregnant/lactating women
* Inadequate contraception
* Inability/unwillingness to comply with protocol
* Prior splenectomy (MF non-TD cohorts)
* Splenic irradiation within 3 months
* Active or chronic HIV, Hepatitis B/C infection
* Active clinically significant infection (until recovery ≥2 weeks)
* Anemia deemed clinically significant (iron/B12/folate deficiency, hemolytic anemia)
* Major bleeding event (≥2 g/dL Hgb drop or ≥2 units transfused in last 6 months)
* Liver cirrhosis Child-Pugh B or C
* GI impairment affecting absorption (unresolved nausea, vomiting, diarrhea \>CTCAE grade 1)
* Rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption (Arm 3)
* Hypersensitivity to ruxolitinib formulation (Arm 3)
* History of PML (Arm 3)
* Significant cardiac disease (recent MI/angina, QTcF \>500 ms \[\>450 ms in France/Germany\], uncontrolled arrhythmia, etc.)
* Ongoing uncontrolled hypertension
* Severe/uncontrolled comorbidities
* Systemic anticancer treatment (other than ruxolitinib for Arm 2, HU/ANA up to 24h prior) \<2 weeks or \<5 half-lives prior
* Prior treatment with any BET inhibitor
* Hematopoietic growth factor or androgenic steroids \<4 weeks prior
* Systemic corticosteroids ≥10 mg prednisone equivalent within 4 weeks (exceptions for short courses)
* Concurrent/second malignancy (except certain adequately treated cancers)
* Pregnant/lactating women, or planning pregnancy within protocol-defined window
* Inability/unwillingness to comply with protocol
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
The Leukemia and Lymphoma Society
OTHER
Constellation Pharmaceuticals
INDUSTRY
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Novartis Pharmaceuticals
Role: STUDY_DIRECTOR
Novartis Pharmaceuticals
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Mayo Clinic Arizona
Phoenix, Arizona, United States
UCLA Medical Center
Los Angeles, California, United States
Mayo Clinic Jacksonville
Jacksonville, Florida, United States
Northwestern University - Lurie Comprehensive Cancer Center
Chicago, Illinois, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States
University of Michigan Medical Center
Ann Arbor, Michigan, United States
Washington University School of Medicne Neuromuscular Division Department of Neurology Research
St Louis, Missouri, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
ICAHN School of Medicine at Mount Sinai
New York, New York, United States
Weill Medical College and New York Presbyterian Hospital
New York, New York, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Froedtert & Medical College of Wisconsin
Milwaukee, Wisconsin, United States
UZ Leuven - Campus Gasthuisberg
Leuven, Viaams Braban, Belgium
AZ Sint-Jan Burgge-Oostende AV- Campus Sint-Jan
Bruges, West-Vlaanderen, Belgium
ZNA Stuyvenberg Antwerpen
Antwerp, , Belgium
University of Alberta Hospital
Edmonton, Alberta, Canada
St. Paul's Hospital
Vancouver, British Columbia, Canada
Juravinski Cancer Centre
Hamilton, Ontario, Canada
Princess Margaret Cancer Centre
Toronto, Ontario, Canada
Jewish General Hospital
Montreal, Quebec, Canada
Institut de cancérologie du Gard - Hematologie clinique
Nîmes, Gard, France
CHRU de Lille - Hopital Claude Huriez
Toulouse, Haute-Garonne, France
CHRU de Lille - Hopital Claude Huriez - Maladies du Sang
Lille, Hauts-de-France, France
CHU - Hopital Saint Louis - Centre D'Investigations Clinique
Paris, , France
Institut Gustave Roussy
Villejuif, Île-de-France Region, France
Universitätsklinikum Bonn
Bonn, North Rhine-Westphalia, Germany
Universitätsklinikum Leipzig AöR
Leipzig, Saxony, Germany
Institue of Hematology "L. and A. Seràgnoli"
Bologna, Emilia-Romagna, Italy
Servizio Sanitario Regionale Emilia-Romagna - Azienda Unita Sanitaria Locale (AUSL) di Rimini - Ospedale Infermi di Rimini
Rimini, Emilia-Romagna, Italy
AOU S.Martino, IRCCS, IST-Istituto Nazionale Ricerca Sul Can
Genoa, Liguria, Italy
Ospedale Maggiore Policlinico, Fondazione IRCCS Ca' Granda
Milan, Lombardy, Italy
IRCCS Policlinico San Matteo, Università degli studi di Pavi
Pavia, Lombardy, Italy
Ospedale di Circolo, PO Varese, AO Ospedale di Circolo e Fon
Varese, Lombardy, Italy
Azienda Ospedaliero-Universitaria Careggi
Florence, , Italy
AOU Maggiore della Carità
Novara, , Italy
Maastricht University Medical Center
Maastricht, Limburg, Netherlands
VUmcResearch B.V.
Amsterdam, North Holland, Netherlands
Erasmus Universitair Medisch Centrum Rotterdam
Rotterdam, South Holland, Netherlands
Instytut Hematologii i Transfuzjologii w Warszawie
Warsaw, Masovian Voivodeship, Poland
Uniwersyteckie Centrum Kliniczne
Gdansk, Pomeranian Voivodeship, Poland
Oxford University Hospitals
Headington, Oxford, 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
University College London Hospital's NHS foundation Trust
London, , United Kingdom
Guys and St Thomas' Hospital - Haematology
London, , United Kingdom
The Christie Hospital
Manchester, , United Kingdom
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Stein EM, Fathi AT, Harb WA, Colak G, Fusco A, Mangan JK. Results from phase 1 of the MANIFEST clinical trial to evaluate the safety and tolerability of pelabresib in patients with myeloid malignancies. Leuk Lymphoma. 2024 Apr;65(4):503-510. doi: 10.1080/10428194.2023.2300710. Epub 2024 Jan 23.
Gupta V, Mascarenhas J, Kremyanskaya M, Rampal RK, Talpaz M, Kiladjian JJ, Vannucchi AM, Verstovsek S, Colak G, Dey D, Harrison C. Matching-adjusted indirect comparison of the pelabresib-ruxolitinib combination vs JAKi monotherapy in myelofibrosis. Blood Adv. 2023 Sep 26;7(18):5421-5432. doi: 10.1182/bloodadvances.2023010628.
Mascarenhas J, Kremyanskaya M, Patriarca A, Palandri F, Devos T, Passamonti F, Rampal RK, Mead AJ, Hobbs G, Scandura JM, Talpaz M, Granacher N, Somervaille TCP, Hoffman R, Wondergem MJ, Salama ME, Colak G, Cui J, Kiladjian JJ, Vannucchi AM, Verstovsek S, Curto-Garcia N, Harrison C, Gupta V. MANIFEST: Pelabresib in Combination With Ruxolitinib for Janus Kinase Inhibitor Treatment-Naive Myelofibrosis. J Clin Oncol. 2023 Nov 10;41(32):4993-5004. doi: 10.1200/JCO.22.01972. Epub 2023 Mar 7.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
2018-000579-34
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
CDAK539A12201
Identifier Type: OTHER
Identifier Source: secondary_id
0610-02
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.