Ph+/Bcr-Abl+ ALL Imatinib and Nilotinib Rotational Study

Treatment Clinical Trial

— LAL1408  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01025505
• Other study ID #: LAL1408
• Status: Completed
• Phase: Phase 2
• Start date: June 2012
• Est. completion date: September 1, 2020

Study information

• Verified date: October 2022
• Source: Gruppo Italiano Malattie EMatologiche dell'Adulto
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: September 1, 2020
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Stem Cell Transplantation
• Treatment

Intervention

Drug:
• Nilotinib
The dose of NIL is 800 mg daily (400 mg twice daily). It must be adapted according to specific guidelines in case of adverse events (AE). It cannot be increased.
• Imatinib
The dose of IM is 600 mg daily (300 mg b.i.d.). It must be adapted according to specific guidelines in case of AE. It cannot be increased.

Locations

Country	Name	City	State
Italy	Azienda Ospedaliera - Nuovo Ospedale "Torrette"	Ancona
Italy	Dipartimento Area Medica P.O.	Ascoli Piceno
Italy	UO Ematologia con trapianto- AOU Policlinico Consorziale di Bari	Bari
Italy	Ospedali Riuniti	Bergamo
Italy	Ist.Ematologia e Oncologia Medica L.e A. Seragnoli	Bologna
Italy	Sezione di Ematologia e Trapianti Spedali Civili	Brescia
Italy	Osp. Reg. A. Di Summa	Brindisi
Italy	Servizio di Ematologia - CTMO - ASL 8 P.O. Binaghi	Cagliari
Italy	Ospedale Ferrarotto	Catania
Italy	Sez.Ematologia e Dip. scienze Biomediche Arcispedale S. Anna	Ferrara
Italy	Clinica Ematologica - Università degli Studi	Genova
Italy	Ospedale Niguarda "Ca' Granda"	Milano
Italy	Sez. di medicina Interna Oncologia ed Ematologia	Modena
Italy	Azienda Ospedaliera Universitaria - Università degli Studi di Napoli "Federico II" - Facoltà di Medicina e Chirurgia	Napoli
Italy	Ospedale di Rilievo Nazionale "A. Cardarelli"	Napoli
Italy	S.C.D.U. Ematologia - DIMECS e Dipartimento Oncologico - Università del Piemonte Orientale Amedeo Avogadro	Novara
Italy	Ospedale S. Luigi Gonzaga	Orbassano
Italy	Università degli Studi di Padova - Ematologia ed Immunologia Clinica	Padova
Italy	Ospedali Riuniti 'Villa Sofia-Cervello'	Palermo
Italy	Div. di Ematologia IRCCS Policlinico S. Matteo	Pavia
Italy	Div. di Ematologia di Muraglia - CTMO Ospedale San Salvatore	Pesaro
Italy	U.O. Ematologia Clinica - Azienda USL di Pescara	Pescara
Italy	Unità Operativa Ematologia e Centro Trapianti - Dipartimento di Oncologia ed Ematologia - AUSL Ospedale di Piacenza	Piacenza
Italy	Ospedale S.Maria delle Croci	Ravenna
Italy	Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli"	Reggio Calabria
Italy	Rimini Ospedale "Infermi"	Rimini
Italy	Complesso Ospedaliero S. Giovanni Addolorata	Roma
Italy	U.O.C. Ematologia - Ospedale S.Eugenio	Roma
Italy	Università Cattolica del Sacro Cuore - Policlinico A. Gemelli	Roma
Italy	Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia	Roma
Italy	Università degli Studi - Policlinico di Tor Vergata	Roma
Italy	U.O. Ematologia, Azienda Ospedaliera Universitaria Senese	Siena
Italy	SCDO Ematologia 2 AOU S.Giovanni Battista	Torino
Italy	Policlinico Universitario - Clinica Ematologia	Udine
Italy	Policlinico G.B. Rossi	Verona

Sponsors (1)

Lead Sponsor	Collaborator
Gruppo Italiano Malattie EMatologiche dell'Adulto

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-Free Survival (DFS)		at 24 months
Secondary	Complete Hematological Response (CHR) rate		at 6, 12 and 24 weeks
Secondary	Complete Cytogenetic Response (CCgR) rate		at 6, 12 and 24 weeks and duration of CCgR
Secondary	Complete molecular response rate (CMR)		at 12 and 24 weeks and duration of CMolR
Secondary	Type and number of BCR-ABL kinase domain mutations		developing during and after the study
Secondary	Relationship between the response, biomarkers and gene expression profile (GEP)		At the end of study
Secondary	Event-Free Survival (EFS) and Overall Survival (OS)		defined as the time from the 1st dose of corticosteroids to death or last contact
Secondary	Side effects, adverse events (AE) and serious AE (SAE)		At the end of study

External Links

•   GIMEMA Foundation website