Etude : MANIFEST / CPI 0610-02



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Acronyme
Nom
Traitement
Type d'étude
MÀJ
Présentation de l'étude
Acronyme : MANIFEST

Nom : CPI 0610-02

Traitement :

Type d'étude : Hors ciblage moléculaire

Dernière MÀJ : 10/10/2019
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : A Phase 1/2 Study of CPI-0610, a Small Molecule Inhibitor of BET Proteins: Phase 1 (in Patients With Hematological Malignancies) and Phase 2 (Dose Expansion of CPI-0610 With and Without Ruxolitinib in Patients With Myelofibrosis)

Spécialité : Tissus lymphoïde, hématopoïétique et apparentés
Localisation : C96 - Tumeurs malignes des tissus lymphoïde, hématopoïétique et apparentés, autres et non précisées
Schéma
Phase
Stade
Ligne(s)
Informations complémentaires
Schéma : Phase 1 Part (Complete): Open-label, sequential dose escalation study of CPI-0610 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.


Study arms:
- Experimental: Arm 1: Prior JAKi (JAK inhibitor) Monotherapy Arm
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.(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. (CPI-0610 alone)
Intervention: Drug: CPI-0610

- Experimental: 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. (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. (CPI-0610 + Ruxolitinib)
Interventions:
Drug: CPI-0610
Drug: Ruxolitinib

- Experimental: Arm 3: JAKi Naïve Combination Arm
• Open to patients with MF who are anemic (i.e., Hemoglobin (Hgb) <10g/dL) and who have not previously received a JAKi. (CPI-0610 + Ruxolitinib)
Interventions:
Drug: CPI-0610
Drug: Ruxolitinib


Current primary outcome:
- Phase 2 Part: Evaluate spleen response [ Time Frame: By imaging after 24 weeks ]
- Phase 2 Part: Evaluate the RBC (Red Blood Cell) transfusion independence rate [ Time Frame: Absence of RBC transfusion and no hemoglobin level below 8 g/dL in the prior 12 weeks ]

Current secondary outcomes:
- Phase 2 Part: Evaluate the duration of spleen response by imaging [ Time Frame: By palpation and imaging after 24 weeks ]
- Phase 2 Part: Evaluate response category rate [ Time Frame: Rate of response by IWG-MRT after 24 weeks ]
- Phase 2 Part: Evaluate the change in patient reported outcomes [ Time Frame: Changes from baseline in the total symptom score (MFSAF v4.0) and PGIC after 24 weeks ]
- Phase 2 Part: Evaluate the rate of RBC transfusion and the RBC transfusion dependence rate [ Time Frame: Average number of RBC units per subject-month ]
- Phase 2 Part: Pharmacokinetic parameters of CPI-0610 and ruxolitinib: AUC and Cmax [ Time Frame: Assessed during cycle 1 (first 21 days on study) ]

Phase : I/II

Stade : NA

NA
Informations libres de droit
Critères d'inclusion
Critères de non-inclusion
Informations libres de droit
Critères d'inclusion et de non-inclusion
Critères d'inclusion : - Adult (aged ≥ 18 years)
- Phase 2 part: Patients with confirmed diagnosis of MF who meet all of the following criteria:
* Dynamic International Prognostic Scoring System (DIPSS; see Appendix 3) risk category of intermediate-1 or higher.
* 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
- 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:
- Palpable spleen ≥ 5 cm that is below the costal margin on physical examination OR RBC transfusion dependent (defined as an average of ≥2 units of RBC transfusions per month over the 12 weeks prior to enrollment)
- 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
- Monotherapy Arm (Arm 1): Previously treated with a JAK inhibitor and be intolerant, resistant, refractory or lost response to the JAK inhibitor
- Combination Arm (Arm 2): Must have received single agent ruxolitinib and be on a stable dose for a minimum 8 weeks

For Arm 3 (JAK inhibitors naïve) the following criteria should be considered:
- Platelet count ≥ 100 x 10^9/L without the assistance of thrombopoietic factors or transfusions
- Palpable spleen ≥ 5 cm that is below the costal margin on physical examination
- Anemic, defined as a hemoglobin < 10g/dL
- At least 2 symptoms measurable (score ≥ 3) or a total score of ≥ 10 using the MFSAF v4.0
- No prior treatment with JAKi allowed

Critères de non-inclusion : - 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 CPI-0610 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.
NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
NCT02158858
Promoteur :
CONSTELLATION PHARMACEUTICALS
Type de sponsor : Industriel
USA - USA
00000 HORS FRANCE

Coordonnateur :
Centre investigateur
Investigateur
TEC / ARC / IDE
État
MÀJ
Informations relatives aux investigateurs
Centre investigateur :
Centre Hospitalier Universitaire de Lille - 2 Avenue Oscar Lambret - 59000 LILLE

Investigateur :
Docteur Nathalie CAMBIER

TEC / ARC / IDE :
Secrétariat de recherche
fanny.miquel@
chru-lille.fr
03.20.44.57.13

Ouverture de l'essai : OUVERT

MAJ : 10/10/2019