MedPath

Treatment of Adult Ph+ LAL With BMS-354825

Phase 2
Completed
Conditions
Lymphoblastic Leukemia, Acute
Registration Number
NCT00391989
Lead Sponsor
Gruppo Italiano Malattie EMatologiche dell'Adulto
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
53
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

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Primary Outcome Measures
NameTimeMethod
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
Secondary Outcome Measures
NameTimeMethod
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
The Best Cytogenetic Response Obtained During BMS Treatment Within Day +85, Whenever Achieved From the Start of the Experimental Drug;End of study
the Cumulative Incidence of Relapse;End of study
The Incidence of Grade >2 CTC-NCI Side Effects and Toxicities;End of study
the Best Molecular Response Obtained During BMS Treatment Within Day +85, Whenever Achieved From the Start of the Experimental Drug;End of study
OS, Defined as the Time Interval Between Inclusion and Death for Any Cause.End of study

Trial Locations

Locations (36)

Presidio Ospedaliero "C. e G.Mazzoni"

🇮🇹

Ascoli Piceno, Italy

Ist.Ematologia e Oncologia Medica L.e A. Seragnoli

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Bologna, Italy

Sez.Ematologia e Dip. scienze Biomediche Arcispedale S. Anna

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Ferrara, Italy

Azienda Ospedaliera Pugliese Ciaccio

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Catanzaro, Italy

Divisione Ematologia 1 - Azienda Ospedaliera Universitaria "San Martino"

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Genova, Italy

Ematologia Università Federico II

🇮🇹

Napoli, Italy

U.O. Ematologia Clinica - Azienda USL di Pescara

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Pescara, Italy

Istituto di Ematologia- Ospedale San Carlo

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Potenza, Italy

Ospedale S.Maria delle Croci

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Ravenna, Italy

Policlinico Universitario

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Udine, Italy

Ospedale Sant'Anna-17

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Ronciglione, Viterbo, Italy

Nuovo Ospedale "Torrette"

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Ancona, Italy

Ospedale San Donato USL 8

🇮🇹

Arezzo, Italy

Università degli Studi di Bari

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Bari, Italy

Azienda Spedali Civili

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Brescia, Italy

Osp. Reg. A. Di Summa

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Brindisi, Italy

Servizio di Ematologia - CTMO - ASL 8 P.O. Binaghi

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Cagliari, Italy

Università di Catania - Cattedra di Ematologia - Ospedale "Ferrarotto"

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Catania, Italy

Ospedale Niguarda " Ca Granda"

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Milano, Italy

Sez. di medicina Interna Oncologia ed Ematologia

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Modena, Italy

Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli" - Div. TERE

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Napoli, Italy

Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli"

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Napoli, Italy

Ospedale S. Luigi Gonzaga

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Orbassano, Italy

Dip. Oncologico "La Maddalena"

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Palermo, Italy

Div. di Ematologia - A.O. "V. Cervello"

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Palermo, Italy

Università degli Studi di Palermo - A.U. Policlinico

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Palermo, Italy

Div. di Ematologia IRCCS Policlinico S. Matteo

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Pavia, Italy

Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli"

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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

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San Giovanni Rotondo, Italy

Serv. di Ematologia Ist. di Ematologia ed Endocrinologia

🇮🇹

Sassari, Italy

Policlinico G.B. Rossi

🇮🇹

Verona, Italy

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