Clinical trial NCT01025505: Ph+/Bcr-Abl+ ALL Imatinib and Nilotinib Rotational Study
Official title: Front-line Treatment of Ph Positive (Ph+)/Bcr-Abl Positive Acute Lymphoblastic Leukemia (ALL) With Two Tyrosine Kinase Inhibitors (TKI) (Imatinib and Nilotinib). A Phase II Exploratory Multicentric Study in Elderly Patients and in Patients Unfit for Program of Intensive Therapy and Allogeneic Stem Cell Transplantation. GIMEMA Protocol LAL1408. EudraCT 2009-01327122
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Treatment
Stem Cell Transplantation
Keywords: Untreated Ph+ ALL unfit for intense therapy and allo SCT
Lead sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto
Sponsor class: OTHER
First posted: 2009-12-03
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is an open-label, multicentric, exploratory, single arm, phase II study of adults who are either more than 60 years old, or are unfit for intensive chemotherapy and allo SCT. The patients are treated with NILOTINIB, administered orally twice daily, for 6 weeks (Course A) followed by IMATINIB, administered orally twice daily, for other 6 weeks (Course B).The courses will be repeated (rotated) for a total of 4 times or until relapse, or until it is in the interest of the patients. Prednisone (P) will be administered to all patients for 7-14 days, before TKIs, so as to make it possible to wait for the results of cytogenetic and molecular tests, and to evaluate the response to P alone, hence for another 21 days. Intrathecal therapy (IT) with MTX/AraC/DEX is mandatory, monthly, in patients without clinical-cytologic evidence of meningeal involvement, while in patients with CNS involvement it is performed twice weekly until clearance of leukemic cells, hence once weekly. IM will be administered at the dosage of 600 mg daily (300 mg twice daily) and Nilotinib at the dosage of 800 mg daily (400 mg twice daily) in all courses.

All patients are scheduled to receive at least 4 courses of either drugs, for a total of 4 courses (4 x 6 = 24 weeks). After 4 courses, patients are either allowed to continue the treatment until relapse or progression, if it is in their interest, or to discontinue the treatment and receive other therapies.


Eligibility criteria: Inclusion Criteria:

* Previously untreated Ph+ ALL more than 60 years old or more than 18 years old, but unfit for program of intensive therapy and allogeneic SCT

Primary outcomes:
measure: Disease-Free Survival (DFS)
timeFrame: at 24 months
Secondary outcomes:
measure: Complete Hematological Response (CHR) rate
timeFrame: at 6, 12 and 24 weeks
measure: Complete Cytogenetic Response (CCgR) rate
timeFrame: at 6, 12 and 24 weeks and duration of CCgR
measure: Complete molecular response rate (CMR)
timeFrame: at 12 and 24 weeks and duration of CMolR
measure: Type and number of BCR-ABL kinase domain mutations
timeFrame: developing during and after the study
measure: Relationship between the response, biomarkers and gene expression profile (GEP)
timeFrame: At the end of study
measure: Event-Free Survival (EFS) and Overall Survival (OS)
timeFrame: defined as the time from the 1st dose of corticosteroids to death or last contact
measure: Side effects, adverse events (AE) and serious AE (SAE)
timeFrame: At the end of study
Other outcomes:
Locations:
city: Ancona
country: Italy
facility: Azienda Ospedaliera - Nuovo Ospedale "Torrette"
city: Ascoli Piceno
country: Italy
facility: Dipartimento Area Medica P.O.
city: Bari
country: Italy
facility: UO Ematologia con trapianto- AOU Policlinico Consorziale di Bari
city: Bergamo
country: Italy
facility: Ospedali Riuniti
city: Bologna
country: Italy
facility: Ist.Ematologia e Oncologia Medica L.e A. Seragnoli
city: Brescia
country: Italy
facility: Sezione di Ematologia e Trapianti Spedali Civili
city: Brindisi
country: Italy
facility: Osp. Reg. A. Di Summa
city: Cagliari
country: Italy
facility: Servizio di Ematologia - CTMO - ASL 8 P.O. Binaghi
city: Catania
country: Italy
facility: Ospedale Ferrarotto
city: Ferrara
country: Italy
facility: Sez.Ematologia e Dip. scienze Biomediche Arcispedale S. Anna
city: Genova
country: Italy
facility: Clinica Ematologica - Università degli Studi
city: Milano
country: Italy
facility: Ospedale Niguarda "Ca' Granda"
city: Modena
country: Italy
facility: Sez. di medicina Interna Oncologia ed Ematologia
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria - Università degli Studi di Napoli "Federico II" - Facoltà di Medicina e Chirurgia
city: Napoli
country: Italy
facility: Ospedale di Rilievo Nazionale "A. Cardarelli"
city: Novara
country: Italy
facility: S.C.D.U. Ematologia - DIMECS e Dipartimento Oncologico - Università del Piemonte Orientale Amedeo Avogadro
city: Orbassano
country: Italy
facility: Ospedale S. Luigi Gonzaga
city: Padova
country: Italy
facility: Università degli Studi di Padova - Ematologia ed Immunologia Clinica
city: Palermo
country: Italy
facility: Ospedali Riuniti 'Villa Sofia-Cervello'
city: Pavia
country: Italy
facility: Div. di Ematologia IRCCS Policlinico S. Matteo
city: Pesaro
country: Italy
facility: Div. di Ematologia di Muraglia - CTMO Ospedale San Salvatore
city: Pescara
country: Italy
facility: U.O. Ematologia Clinica - Azienda USL di Pescara
city: Piacenza
country: Italy
facility: Unità Operativa Ematologia e Centro Trapianti - Dipartimento di Oncologia ed Ematologia - AUSL Ospedale di Piacenza
city: Ravenna
country: Italy
facility: Ospedale S.Maria delle Croci
city: Reggio Calabria
country: Italy
facility: Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli"
city: Rimini
country: Italy
facility: Rimini Ospedale "Infermi"
city: Roma
country: Italy
facility: Complesso Ospedaliero S. Giovanni Addolorata
city: Roma
country: Italy
facility: Università degli Studi - Policlinico di Tor Vergata
city: Roma
country: Italy
facility: U.O.C. Ematologia - Ospedale S.Eugenio
city: Roma
country: Italy
facility: Università Cattolica del Sacro Cuore - Policlinico A. Gemelli
city: Roma
country: Italy
facility: Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia
city: Siena
country: Italy
facility: U.O. Ematologia, Azienda Ospedaliera Universitaria Senese
city: Torino
country: Italy
facility: SCDO Ematologia 2 AOU S.Giovanni Battista
city: Udine
country: Italy
facility: Policlinico Universitario - Clinica Ematologia
city: Verona
country: Italy
facility: Policlinico G.B. Rossi
Study officials:
affiliation: Policlinico Sant'Orsola
name: Michele Baccarani
role: PRINCIPAL_INVESTIGATOR
References: