Treatment of Adult Ph+ LAL With BMS-354825

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Lymphoblastic Leukemia, Acute	Drug: Dasatinib	Phase 2

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	53 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
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 Start Date :	September 2006
Actual Primary Completion Date :	September 2008
Actual Study Completion Date :	September 2008

Arms and Interventions

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Outcome Measures

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Primary Outcome Measures :

1. 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). [ Time Frame: End of the study, up to day 85 ]

Secondary Outcome Measures :

1. The Incidence of Grade >2 CTC-NCI Side Effects and Toxicities; [ Time Frame: End of study ]
2. The Best Cytogenetic Response Obtained During BMS Treatment Within Day +85, Whenever Achieved From the Start of the Experimental Drug; [ Time Frame: End of study ]
3. the Best Molecular Response Obtained During BMS Treatment Within Day +85, Whenever Achieved From the Start of the Experimental Drug; [ Time Frame: End of study ]
4. DFS, Defined as the Time Interval Between the Evaluation of HCR and Hematological Relapse of the Disease or Death in First HCR; [ Time Frame: End of study ]
5. the Cumulative Incidence of Relapse; [ Time Frame: End of study ]
6. OS, Defined as the Time Interval Between Inclusion and Death for Any Cause. [ Time Frame: End of study ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

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Locations

Italy
Ospedale Sant'Anna-17
Ronciglione, Viterbo, 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" - Div. TERE
Napoli, Italy
Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli"
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 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, Italy

Sponsors and Collaborators

Gruppo Italiano Malattie EMatologiche dell'Adulto

Investigators

Principal Investigator:	Robin Foà, MD, PhD	Università degli Studi di Roma "La Sapienza", Dipartimento di Biotecnologie Cellulari ed Ematolgia

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Foà 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.

Messina M, Chiaretti S, Iacobucci I, Tavolaro S, Lonetti A, Santangelo S, Elia L, Papayannidis C, Paoloni F, Vitale A, Guarini A, Martinelli G, Foà 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.

Responsible Party:	Gruppo Italiano Malattie EMatologiche dell'Adulto
ClinicalTrials.gov Identifier:	NCT00391989 History of Changes
Other Study ID Numbers:	LAL1205
First Posted:	October 25, 2006
Results First Posted:	January 26, 2015
Last Update Posted:	January 4, 2017
Last Verified:	November 2016

Keywords provided by Gruppo Italiano Malattie EMatologiche dell'Adulto:

Ph+ Acute Lymphoblastic Leukaemia; Dasatinib; targeted therapy; Patients with Ph positive and or BCR ABL positive ALL

Additional relevant MeSH terms:

Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases	Immunoproliferative Disorders; Immune System Diseases; Dasatinib; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action