Treatment of Adult Ph+ LAL With BMS-354825

Lymphoblastic Leukemia, Acute Clinical Trial

Official title:

A Phase II Multicenter Study on the Treatment of Adult de Novo Philadelphia Chromosome Positive (Ph+) Acute Lymphoblastic Leukemia (ALL) With the Protein Tyrosine Kinase Inhibitor BMS-354825. EudraCT Number 2005-005107-42.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00391989
• Other study ID #: LAL1205
• Status: Completed
• Phase: Phase 2
• First received: October 24, 2006
• Last updated: January 22, 2015
• Start date: September 2006
• Est. completion date: September 2008

Study information

• Verified date: January 2015
• Source: Gruppo Italiano Malattie EMatologiche dell'Adulto
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial Summary

The primary objective of the trial is to estimate the activity of BMS-354825 (Dasatinib) in de novo adult Ph+ ALL patients in terms of hematological complete remission (HCR) rate.

Description:

This open label phase II study of Dasatinib will enroll adult de novo Ph+ ALL patients. A minimum of 48 cases will be required to complete the study. Accrual is expected to be completed in 18 months. The study will be considered completed for patients in HCR after completion of a total of 12 weeks of treatment. After completion patients will go off study and will be treated according to the best treatment option for Ph+ ALL patients in 1st HCR. The enrollment in the post-remissional phase of the current GIMEMA LAL protocol will be suggested.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: September 2008
• Est. primary completion date: September 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with Ph+ and/or BCR/ABL+ ALL

• Age =18 years old

• De novo ALL (within 14 days from diagnosis)

• No prior treatment with any anti-leukemic drugs with the exception of steroids for no more than 14 days (including the 7-day pretreatment already scheduled in the protocol)

• WHO performance status =2

• Absence of central nervous system (CNS) leukemia

• Normal serum level of potassium, total calcium corrected for serum albumin magnesium and phosphorus, or correctable with supplements

• ALT and AST =2.5 x ULN or =5.0 x ULN if considered due to leukemia

• Alkaline phosphatase =2.5 x ULN unless considered to leukemia

• Serum bilirubin =2 x ULN

• Serum creatinine =3 x ULN

• Serum amylase =1.5 x ULN and serum lipase =1.5 x ULN

• Normal cardiac function

• Written informed consent prior to any study procedures being performed.

Exclusion Criteria:

• Impaired cardiac function, including any one of the following:

• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BMS-354825 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhoea, malabsorption syndrome, or small bowel resection)

• Use of therapeutic warfarin

• Acute or chronic liver or renal disease considered unrelated to leukemia

• Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes, active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol

• Treatment with any hematopoietic colony-stimulating growth factors (e.g., G-CSF, GM¬CSF) =1 week prior to starting study drug

• Patients who are currently receiving treatment with any of the medications listed in "Appendix F" and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug. The medications listed in "Appendix F" have the potential to prolong the QT interval.

• Patients who have received any anti-leukemic agents and treatments including steroids for more than 14 days including 7 days pretreatment that is part of the protocol

• Patients who have received any investigational drug in the last 2 weeks

• Patients who have undergone major surgery =2 weeks prior to starting study drug or who have not recovered from side effects of such therapy

• Patients who are pregnant or breast feeding, or adults of reproductive potential not employing an effective method of birth control. (Women of childbearing potential must have a negative serum pregnancy test within 48 hrs prior to administration of BMS-354825). Post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug

• Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory)

• Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention

• Non compliant to oral medication patients.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia, Lymphoid
• Lymphoblastic Leukemia, Acute
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Dasatinib

Locations

Country	Name	City	State
Italy	Nuovo Ospedale "Torrette"	Ancona
Italy	Ospedale San Donato USL 8	Arezzo
Italy	Presidio Ospedaliero "C. e G.Mazzoni"	Ascoli Piceno
Italy	Università degli Studi di Bari	Bari
Italy	Ist.Ematologia e Oncologia Medica L.e A. Seragnoli	Bologna
Italy	Azienda Spedali Civili	Brescia
Italy	Osp. Reg. A. Di Summa	Brindisi
Italy	Servizio di Ematologia - CTMO - ASL 8 P.O. Binaghi	Cagliari
Italy	Università di Catania - Cattedra di Ematologia - Ospedale "Ferrarotto"	Catania
Italy	Azienda Ospedaliera Pugliese Ciaccio	Catanzaro
Italy	Sez.Ematologia e Dip. scienze Biomediche Arcispedale S. Anna	Ferrara
Italy	Divisione Ematologia 1 - Azienda Ospedaliera Universitaria "San Martino"	Genova
Italy	Ospedale Niguarda " Ca Granda"	Milano
Italy	Sez. di medicina Interna Oncologia ed Ematologia	Modena
Italy	Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli"	Napoli
Italy	Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli" - Div. TERE	Napoli
Italy	Ematologia Università Federico II	Napoli
Italy	Ospedale S. Luigi Gonzaga	Orbassano
Italy	Dip. Oncologico "La Maddalena"	Palermo
Italy	Div. di Ematologia - A.O. "V. Cervello"	Palermo
Italy	Università degli Studi di Palermo - A.U. Policlinico	Palermo
Italy	Div. di Ematologia IRCCS Policlinico S. Matteo	Pavia
Italy	U.O. Ematologia Clinica - Azienda USL di Pescara	Pescara
Italy	Istituto di Ematologia- Ospedale San Carlo	Potenza
Italy	Ospedale S.Maria delle Croci	Ravenna
Italy	Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli"	Reggio Calabria
Italy	Ospedale S. Camillo	Rome
Italy	Ospedale S.Eugenio	Rome
Italy	Università Cattolica del Sacro Cuore	Rome
Italy	Università degli Studi di Roma "La Sapienza"	Rome
Italy	Università degli Studi di Tor Vergata	Rome
Italy	Ospedale Sant'Anna-17	Ronciglione	Viterbo
Italy	Ospedale Casa Sollievo della sofferenza	San Giovanni Rotondo
Italy	Serv. di Ematologia Ist. di Ematologia ed Endocrinologia	Sassari
Italy	Policlinico Universitario	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	Rate of Hematological Complete Remission (HCR) Obtained During the BMS Induction Treatment Within Day +85 From the Start of BMS (i.e., Whenever Achieved From the Start of the Experimental Drug).		End of the study, up to day 85	No
Secondary	The Incidence of Grade >2 CTC-NCI Side Effects and Toxicities;		End of study	No
Secondary	The Best Cytogenetic Response Obtained During BMS Treatment Within Day +85, Whenever Achieved From the Start of the Experimental Drug;		End of study	No
Secondary	the Best Molecular Response Obtained During BMS Treatment Within Day +85, Whenever Achieved From the Start of the Experimental Drug;		End of study	No
Secondary	DFS, Defined as the Time Interval Between the Evaluation of HCR and Hematological Relapse of the Disease or Death in First HCR;		End of study	No
Secondary	the Cumulative Incidence of Relapse;		End of study	No
Secondary	OS, Defined as the Time Interval Between Inclusion and Death for Any Cause.		End of study	No