The following info and data is provided "as is" to help patients around the globe.
We do not endorse or review these studies in any way.
Brief Title: Evaluation of CPX-351 Monotherapy in Acute Myeloid Leukemia Secondary to Myeloproliferative Neoplasm
Official Title: A Phase II Study of CPX-351 Monotherapy in Acute Myeloid Leukemia
Study ID: NCT04992949
Brief Summary: The three classic myeloproliferative neoplasms (MPNs) include polycythemia Vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). The natural history of these MPNs is the possible progression to acute myeloid leukemia (MPN-blast phase) at variable percentage depending the entity. Leukemic transformation of MPN occurs in 8% to 23% of primary myelofibrosis (PMF) patients in the first 10 years after diagnosis and in 4% to 8% of polycythemia vera (PV) and essential thrombocytosis (ET) patients within 18 years after diagnosis. The risk for leukemic transformation is increased by exposure to cytotoxic chemotherapy. The molecular pathogenesis of MPN-blast phase remains an area of active research. The prognosis of blast phase MPNs is very poor : approximately 50% of the patients are deemed eligible for intensive treatment (ie. conventional induction chemotherapy regimen with anthracyclines and cytarabine). The patients who are not fit for such intensive treatment approach due to age or comorbidities, are treated with Hypomethylating agents, low dose palliative chemotherapy, or supportive care. Nevertheless, there is a need for more effective and better tolerated treatment approaches in order to increase the response rate and hence, the transplant rates which should translate into improved survival. CPX-351 is a new formulation of cytarabine and daunorubicin encapsulated at a fixed 5:1 molar-ratio in liposomes that exploits molar ratio-dependent drug-drug synergy to enhance antileukemic efficacy. Based on similarities between post-myelodysplastic syndrome (MDS) and post-MPN secondary AML in terms of disease resistance to chemotherapy, of fragile patient profile, The hypotheses made is that CPX-351 may improve the results of induction chemotherapy without increasing its toxicity and therefore may increase the proportion of patients who could benefit from an allogeneic Stem Cell Transplantation (SCT).
Detailed Description: The primary objective of the study is to evaluate the Complete Remission (CR/CRi) rate after treatment with CPX-351 in patients with AML secondary to myeloproliferative neoplasms (post-MPN AML). The hypotheses made is that treatment with CPX-351 will improve the historical response rate from 45% to 65%. The exact single stage Phase II design was used to calculate the number of patients. The null hypothesis H0 is that the probability p of CR/CRi rate with CPX351 is equal or lower than the historical rate p0 of 45% (H0: p≤p0). The alternative hypothesis H1 that is p\>p0, supposing that CR/CRi rate will be 65% using CPX351. Considering an alpha risk of 5% and a power of 80%, 42 patients will be included, and H0 will be rejected if at least 25 patients achieve CR /CRi (R-project, "clinfun" package). Inclusion period : 36 months Treatment period (6 months) : * one or two cycles of induction treatment with CPX-351 (depending on CR/CRi achieving). If CR/CRi is not achieved following the induction phase, patients will go off study. * 2 courses of consolidation therapy with CPX-351 (patients for whom an allo-SCT is planned will receive a maximum of one consolidation cycle) All included patients will be followed for 60 days after the End of Treatment (EOT) or at the date of allogeneic stem cell transplantation when appropriate : the day-60 follow-up visit will be the End Of Study (EOS) visit. The anti-leukemic chemotherapy administrated after relapse will be recorded. After completion of the study, subjects will be followed-up at regular intervals (every 3 months) to collect information on the subjects' survival and disease (relapse) status. Survival status will be collected until death, or withdrawal of consent or lost to follow-up, whichever occurs first..
Minimum Age: 18 Years
Eligible Ages: ADULT, OLDER_ADULT
Sex: ALL
Healthy Volunteers: No
AMIENS - CHU Amiens Picardie, Amiens, , France
ANGERS - CHU - Maladies du sang, Angers, , France
AVIGNON - Centre Hospitalier, Avignon, , France
BAYONNE - CH de la Côte Basque - Hématologie, Bayonne, , France
AVICENNE - Centre de Recherche Clinique, Bobigny, , France
BREST - Hôpital Morvan, Brest, , France
CAEN - CHU Caen - IHBN, Caen, , France
CLAMART - Hôpital d'Instruction des Armées de Percy, Clamart, , France
Clermont-Ferrand - Chu Estaing, Clermont-Ferrand, , France
CRETEIL - CHU Henri Mondor, Créteil, , France
Grenoble - CHUGA - Hématologie Clinique, Grenoble, , France
LILLE CHU - Hôpital Claude Huriez, Lille, , France
LIMOGES - CHU Dupuytren 1, Limoges, , France
LYON-Centre Léon Bérard, Lyon, , France
MARSEILLE - Institut Paoli-Calmettes, Marseille, , France
MONTPELLIER - Hôpital Saint-Eloi - Hématologie Clinique, Montpellier, , France
NANTES - Hôpital Hôtel Dieu - Hématologie Clinique, Nantes, , France
NICE - Centre Antoine Lacassagne, Nice, , France
NICE - CHU - Hopital Archet 1, Nice, , France
NIMES - CHU Caremeau, Nîmes, , France
ORLEANS - CHR - Hématologie, Orléans, , France
Paris St Antoine, Paris, , France
Paris Saint Louis, Paris, , France
BORDEAUX - Hôpital Haut-Levêque, Pessac, , France
LYON HCL - CH Lyon Sud, Pierre-Bénite, , France
POITIERS - Hôpital La Milétrie - Hématologie Clinique, Poitiers, , France
REIMS - Hôpital Robert Debré - Hématologie Clinique, Reims, , France
RENNES - Hôpital Pontchaillou - Hématologie, Rennes, , France
Strasbourg - Icans, Strasbourg, , France
Toulouse - IUCT Oncopole - Service d'Hématologie, Toulouse, , France
TOURS - Hôpital Bretonneau, Tours, , France
NANCY - CHU de Brabois, Vandœuvre-lès-Nancy, , France
VERSAILLES - Hôpital André Mignot, Versailles, , France
Institut Gustave Roussy, Villejuif, , France
Name: Jérôme REY, MD
Affiliation: French Innovative Leukemia Organisation
Role: PRINCIPAL_INVESTIGATOR