Ph+/Bcr-Abl+ ALL Imatinib and Nilotinib Rotational Study (LAL1408)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gruppo Italiano Malattie EMatologiche dell'Adulto
ClinicalTrials.gov Identifier:
NCT01025505
First received: December 1, 2009
Last updated: July 25, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Treatment
Stem Cell Transplantation
Drug: Nilotinib
Drug: Imatinib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Gruppo Italiano Malattie EMatologiche dell'Adulto:

Primary Outcome Measures:
  • Disease-Free Survival (DFS) [ Time Frame: at 24 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Complete Hematological Response (CHR) rate [ Time Frame: at 6, 12 and 24 weeks ] [ Designated as safety issue: No ]
  • Complete Cytogenetic Response (CCgR) rate [ Time Frame: at 6, 12 and 24 weeks and duration of CCgR ] [ Designated as safety issue: No ]
  • Complete molecular response rate (CMR) [ Time Frame: at 12 and 24 weeks and duration of CMolR ] [ Designated as safety issue: No ]
  • Type and number of BCR-ABL kinase domain mutations [ Time Frame: developing during and after the study ] [ Designated as safety issue: No ]
  • Relationship between the response, biomarkers and gene expression profile (GEP) [ Time Frame: At the end of study ] [ Designated as safety issue: No ]
  • Event-Free Survival (EFS) and Overall Survival (OS) [ Time Frame: defined as the time from the 1st dose of corticosteroids to death or last contact ] [ Designated as safety issue: No ]
  • Side effects, adverse events (AE) and serious AE (SAE) [ Time Frame: At the end of study ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 40
Study Start Date: June 2012
Estimated Study Completion Date: January 2018
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    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.
    Drug: 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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01025505

Locations
Italy
Azienda Ospedaliera - Nuovo Ospedale "Torrette"
Ancona, Italy
Dipartimento Area Medica P.O.
Ascoli Piceno, Italy, 63100
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, 21125
Osp. Reg. A. Di Summa
Brindisi, Italy
Servizio di Ematologia - CTMO - ASL 8 P.O. Binaghi
Cagliari, Italy
Ospedale Ferrarotto
Catania, Italy, 95124
Sez.Ematologia e Dip. scienze Biomediche Arcispedale S. Anna
Ferrara, Italy, 44100
Clinica Ematologica - Università degli Studi
Genova, Italy
Ospedale Niguarda "Ca' Granda"
Milano, Italy, 20122
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, 10043
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, 27100
Div. di Ematologia di Muraglia - CTMO Ospedale San Salvatore
Pesaro, Italy
U.O. Ematologia Clinica - Azienda USL di Pescara
Pescara, Italy, 65100
Unità Operativa Ematologia e Centro Trapianti - Dipartimento di Oncologia ed Ematologia - AUSL Ospedale di Piacenza
Piacenza, Italy
Ospedale S.Maria delle Croci
Ravenna, Italy, 48100
Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli"
Reggio Calabria, Italy
Rimini Ospedale "Infermi"
Rimini, Italy
Complesso Ospedaliero S. Giovanni Addolorata
Roma, Italy, 00184
U.O.C. Ematologia - Ospedale S.Eugenio
Roma, Italy
Università degli Studi - Policlinico di Tor Vergata
Roma, Italy, 21100
Università Cattolica del Sacro Cuore - Policlinico A. Gemelli
Roma, Italy
Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia
Roma, Italy
U.O. Ematologia, Azienda Ospedaliera Universitaria Senese
Siena, Italy, 53100
SCDO Ematologia 2 AOU S.Giovanni Battista
Torino, Italy
Policlinico Universitario - Clinica Ematologia
Udine, Italy, 33100
Policlinico G.B. Rossi
Verona, Italy, 37134
Sponsors and Collaborators
Gruppo Italiano Malattie EMatologiche dell'Adulto
Investigators
Principal Investigator: Michele Baccarani Policlinico Sant'Orsola
  More Information

No publications provided

Responsible Party: Gruppo Italiano Malattie EMatologiche dell'Adulto
ClinicalTrials.gov Identifier: NCT01025505     History of Changes
Other Study ID Numbers: LAL1408
Study First Received: December 1, 2009
Last Updated: July 25, 2013
Health Authority: Italy: The Italian Medicines Agency

Keywords provided by Gruppo Italiano Malattie EMatologiche dell'Adulto:
Untreated Ph+ ALL unfit for intense therapy and allo SCT

Additional relevant MeSH terms:
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Imatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 16, 2014