Clinical trial NCT00391989: Treatment of Adult Ph+ LAL With BMS-354825
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoblastic Leukemia, Acute
Keywords: Ph+ Acute Lymphoblastic Leukaemia
Dasatinib
targeted therapy
Patients with Ph positive and or BCR ABL positive ALL
Lead sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto
Sponsor class: OTHER
First posted: 2006-10-25
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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).
timeFrame: End of the study, up to day 85
Secondary outcomes:
measure: The Incidence of Grade >2 CTC-NCI Side Effects and Toxicities;
timeFrame: End of study
measure: The Best Cytogenetic Response Obtained During BMS Treatment Within Day +85, Whenever Achieved From the Start of the Experimental Drug;
timeFrame: End of study
measure: the Best Molecular Response Obtained During BMS Treatment Within Day +85, Whenever Achieved From the Start of the Experimental Drug;
timeFrame: End of study
measure: DFS, Defined as the Time Interval Between the Evaluation of HCR and Hematological Relapse of the Disease or Death in First HCR;
timeFrame: End of study
measure: the Cumulative Incidence of Relapse;
timeFrame: End of study
measure: OS, Defined as the Time Interval Between Inclusion and Death for Any Cause.
timeFrame: End of study
Other outcomes:
Locations:
city: Ronciglione
country: Italy
facility: Ospedale Sant'Anna-17
state: Viterbo
city: Ancona
country: Italy
facility: Nuovo Ospedale "Torrette"
city: Arezzo
country: Italy
facility: Ospedale San Donato USL 8
city: Ascoli Piceno
country: Italy
facility: Presidio Ospedaliero "C. e G.Mazzoni"
city: Bari
country: Italy
facility: Università degli Studi di Bari
city: Bologna
country: Italy
facility: Ist.Ematologia e Oncologia Medica L.e A. Seragnoli
city: Brescia
country: Italy
facility: Azienda 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: Università di Catania - Cattedra di Ematologia - Ospedale "Ferrarotto"
city: Catanzaro
country: Italy
facility: Azienda Ospedaliera Pugliese Ciaccio
city: Ferrara
country: Italy
facility: Sez.Ematologia e Dip. scienze Biomediche Arcispedale S. Anna
city: Genova
country: Italy
facility: Divisione Ematologia 1 - Azienda Ospedaliera Universitaria "San Martino"
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 di Rilievo Nazionale "A. Cardarelli" - Div. TERE
city: Napoli
country: Italy
facility: Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli"
city: Napoli
country: Italy
facility: Ematologia Università Federico II
city: Orbassano
country: Italy
facility: Ospedale S. Luigi Gonzaga
city: Palermo
country: Italy
facility: Dip. Oncologico "La Maddalena"
city: Palermo
country: Italy
facility: Div. di Ematologia - A.O. "V. Cervello"
city: Palermo
country: Italy
facility: Università degli Studi di Palermo - A.U. Policlinico
city: Pavia
country: Italy
facility: Div. di Ematologia IRCCS Policlinico S. Matteo
city: Pescara
country: Italy
facility: U.O. Ematologia Clinica - Azienda USL di Pescara
city: Potenza
country: Italy
facility: Istituto di Ematologia- Ospedale San Carlo
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: Rome
country: Italy
facility: Ospedale S. Camillo
city: Rome
country: Italy
facility: Ospedale S.Eugenio
city: Rome
country: Italy
facility: Università Cattolica del Sacro Cuore
city: Rome
country: Italy
facility: Università degli Studi di Roma "La Sapienza"
city: Rome
country: Italy
facility: Università degli Studi di Tor Vergata
city: San Giovanni Rotondo
country: Italy
facility: Ospedale Casa Sollievo della sofferenza
city: Sassari
country: Italy
facility: Serv. di Ematologia Ist. di Ematologia ed Endocrinologia
city: Udine
country: Italy
facility: Policlinico Universitario
city: Verona
country: Italy
facility: Policlinico G.B. Rossi
Study officials:
affiliation: Università degli Studi di Roma "La Sapienza", Dipartimento di Biotecnologie Cellulari ed Ematolgia
name: Robin Foà, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Foa R, Vitale A, Vignetti M, Meloni G, Guarini A, De Propris MS, Elia L, Paoloni F, Fazi P, Cimino G, Nobile F, Ferrara F, Castagnola C, Sica S, Leoni P, Zuffa E, Fozza C, Luppi M, Candoni A, Iacobucci I, Soverini S, Mandelli F, Martinelli G, Baccarani M; GIMEMA Acute Leukemia Working Party. Dasatinib as first-line treatment for adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood. 2011 Dec 15;118(25):6521-8. doi: 10.1182/blood-2011-05-351403. Epub 2011 Sep 19.
citation: Messina M, Chiaretti S, Iacobucci I, Tavolaro S, Lonetti A, Santangelo S, Elia L, Papayannidis C, Paoloni F, Vitale A, Guarini A, Martinelli G, Foa R. AICDA expression in BCR/ABL1-positive acute lymphoblastic leukaemia is associated with a peculiar gene expression profile. Br J Haematol. 2011 Mar;152(6):727-32. doi: 10.1111/j.1365-2141.2010.08449.x. Epub 2011 Jan 31.