D-ALBA Frontline Sequential Dasatinib and Blinatumomab in Adult Philadelphia Positive Acute Lymphoblastic Leukemia

Phase 2

• Conditions: Acute Lymphoblastic Leukemia
• Interventions: Drug: Dasatinib; Drug: Blinatumomab

• Registration Number: NCT02744768
• Lead Sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto

Brief Summary

This study aims at exploring the activity of a frontline approach based on dasatinib plus steroids administration as induction treatment, followed by the infusion of Blinatumomab, in adult Ph+ ALL.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-04-11
• Study First Submitted QC: 2016-04-18
• Study First Posted: 2016-04-20
• Study Start: 2017-05-31
• Status Verified: 2018-03
• Last Update Submitted: 2018-03-21
• Last Update Posted: 2018-03-22
• Primary Completion: 2021-06
• Study Completion: 2021-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• Newly diagnosed adult B-precursor Ph+ ALL patients.

• Age greater or equal to18 years,

• Signed written informed consent according to ICH/EU/GCP and national local laws.

• ECOG Performance Status 0 or 1 and/or WHO performance status less or equal to 2.

• Renal and hepatic function as defined below:

  • AST (GOT), ALT (GPT), and AP <2 x upper limit of normal (ULN).
  • Total bilirubin <1.5 x ULN.
  • Creatinine clearance equal or greater than 50 mL/min.

• Pancreatic function as defined below:

  • Serum amylase less or equal to 1.5 x ULN
  • Serum lipase less or equal to1.5 x ULN.

• Normal cardiac function.

• Negative HIV test, negative HBV DNA and HCV RNA.

• Negative pregnancy test in women of childbearing potential.

• Bone marrow specimen from primary diagnosis available.

Read More

Exclusion Criteria

• History of or current relevant CNS pathology (current ≥grade 2 epilepsy, seizure, paresis, aphasia, clinically relevant apoplexia, severe brain injuries, dementia, Parkinson's disease, organic brain syndrome, psychosis).

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

  • LVEF <45% as determined by MUGA scan or echocardiogram.
  • Complete left bundle branch block.
  • Use of a cardiac pacemaker.
  • ST depression of >1mm in 2 or more leads and/or T wave inversions in 2 or more contiguous leads.
  • Congenital long QT syndrome.
  • History of or presence of significant ventricular or atrial arrhythmia.
  • Clinically significant resting bradycardia (<50 beats per minute).
  • QTc >450 msec on screening ECG (using the QTcF formula).
  • Right bundle branch block plus left anterior hemiblock, bifascicular block.
  • Myocardial infarction within 3 months prior to starting Dasatinib.
  • Angina pectoris.

• Other clinically significant heart disease (e.g., congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen).

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

• History of or current autoimmune disease.

• Systemic cancer chemotherapy within 2 weeks prior to study.

• Known hypersensitivity to immunoglobulins or to any other component of the study drug formulation.

• Active malignancy other than ALL with the exception of basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix.

• Active infection, any other concurrent disease or medical conditions that are deemed to interfere with the conduct of the study as judged by the investigator.

• Nursing women or women of childbearing potential not willing to use an effective form of contraception during participation in the study and at least 3 months thereafter or male patients not willing to ensure effective contraception during participation in the study and at least three months thereafter.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment	Blinatumomab	Adult Ph+ ALL (≥18 years old, with no upper age limit) patients will begin treatment with Dasatinib, 140 mg/day, from day 1 to day +84. Prednisone (PDN) will be administered from day -6 to day +0 (during which the presence of the BCR/ABL1 alteration will be established), at escalating doses up to 60 mg/m2; PDN will be continued up to day +24 and progressively tapered up to day +31. HLA typing will be performed immediately after the diagnosis for eligible patients. MRD will be evaluated by RT-PCR at fixed time points (days +22, +45, +57) during the induction and at day +85, the latter for molecular response evaluation.
Treatment	Dasatinib	Adult Ph+ ALL (≥18 years old, with no upper age limit) patients will begin treatment with Dasatinib, 140 mg/day, from day 1 to day +84. Prednisone (PDN) will be administered from day -6 to day +0 (during which the presence of the BCR/ABL1 alteration will be established), at escalating doses up to 60 mg/m2; PDN will be continued up to day +24 and progressively tapered up to day +31. HLA typing will be performed immediately after the diagnosis for eligible patients. MRD will be evaluated by RT-PCR at fixed time points (days +22, +45, +57) during the induction and at day +85, the latter for molecular response evaluation.

Primary Outcome Measures

Name	Time	Method
Number of patients who achieve Minimal Residual Disease (MRD) negativity upon treatment	After 11 months from study entry	In particular, after 2 cycles of blinatumomab. Minimal Residual Disease (MRD) negativity is intended as Complete Molecular Remission (CMR)

Secondary Outcome Measures

Name	Time	Method
Number of months of the CMR	At 12 and 24 months
Number of patients at Complete Molecular Response (CMR)	At day +22, +45, +57 and +85 from study entry
Number of patients in Overall Survival (OS)	At 12 and 24 months
Number of grade >3 adverse events	At 12 and 24 months
Number of patients completing the 2 cycles of blinatumomab and alive in first complete hematologic remission (CHR)	From day +85 at 12 months

Trial Locations

Locations (34)

Az.Ospedaliera S.G.Moscati; 🇮🇹 Avellino, Italy

Ospedale Niguarda " Ca Granda" - SC Ematologia Blocco SUD, Ponti Est, Scala E, 4° piano; 🇮🇹 Milano, Italy

Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli"; 🇮🇹 Napoli, Italy

Dipartimento di Oncologia ed Ematologia S.C. Ematologia 2 A.O. Città della Salute e della Scienza di Torino San Giovanni Battista; 🇮🇹 Torino, Italy

U.O.C. Ematologia e Terapia Cellulare - Ospedale "C. e G. Mazzoni" di Ascoli Piceno; 🇮🇹 Ascoli Piceno, Italy

UO Ematologia con trapianto-Università degli Studi di Bari Aldo Moro; 🇮🇹 Bari, Italy

Azienda Ospedaliera - Papa Giovanni XXIII; 🇮🇹 Bergamo, Italy

Istituto di Ematologia "Lorenzo e A. Seragnoli" - Università degli Studi di Bologna - Policlinico S. Orsola - Malpighi; 🇮🇹 Bologna, Italy

Divisione di Ematologia Ospedale A. Perrino; 🇮🇹 Brindisi, Italy

Università di Catania - Cattedra di Ematologia - Ospedale "Ferrarotto"; 🇮🇹 Catania, Italy

Unità di Ricerca e di Malattie del sangue - Ematologia San Luca Vecchio Pad. 16 - 1° Piano; 🇮🇹 Firenze, Italy

Unità Operative Complesse di Ematologia 1 e 2 Centro Trapianti di Midollo dell'IRCCS AOU San Martino-IST; 🇮🇹 Genova, Italy

ASL Le/1 P.O. Vito Fazzi - U.O. di Ematologia ed UTIE; 🇮🇹 Lecce, Italy

U.O. di Ematologia- Ospedale dell'Angelo - Mestre; 🇮🇹 Mestre, Italy

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico UOC Oncoematologia- Padiglione Marcora 2° piano; 🇮🇹 Milano, Italy

Azienda Ospedaliera Universitaria - Università degli Studi di Napoli "Federico II" - Facoltà di Medicina e Chirurgia; 🇮🇹 Napoli, Italy

S.C.D.U. Ematologia - DIMECS e Dipartimento Oncologico - Università del Piemonte Orientale Amedeo Avogadro; 🇮🇹 Novara, Italy

Dip. di Scienze Cliniche e Biologiche - Ospedale S. Luigi Gonzaga-Medicina Interna 2; 🇮🇹 Orbassano, Italy

U.O. di Oncoematologia -plesso ospedaliero "A. Tortora" di Pagani; 🇮🇹 Pagani, Italy

Ospedali Riuniti "Villa Sofia-Cervello"; 🇮🇹 Palermo, Italy

Sezione di Ematologia ed Immunologia Clinica - Ospedale S.Maria della Misericordia; 🇮🇹 Perugia, Italy

Ematologia Clinica - Azienda USL di Pescara; 🇮🇹 Pescara, Italy

Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli"; 🇮🇹 Reggio Calabria, Italy

Complesso Ospedaliero S. Giovanni Addolorata; 🇮🇹 Roma, Italy

Università degli Studi - Policlinico di Tor Vergata; 🇮🇹 Roma, Italy

Policlinico Umberto I, Hematology Department; 🇮🇹 Rome, Italy

UOC Medicina Trasfusionale e Cellule Staminali Azienda Ospedaliera San Camillo Forlanini; 🇮🇹 Roma, Italy

Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia; 🇮🇹 Rome, Italy

Sezione di Ematologia Cancer Center Humanitas; 🇮🇹 Rozzano, Italy

Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza; 🇮🇹 San Giovanni Rotondo, Italy

Struttura Complessa a Dir. Universitaria-Ematologia e Terapie Cellulari- A.S.O. Ordine Mauriziano, P.O. Umberto I-Ospedale Torino; 🇮🇹 Torino, Italy

Struttura Complessa a Dir. Universitaria-Ematologia e Terapie Cellulari- A.S.O. Ordine Mauriziano, P.O. Umberto I-Ospedale; 🇮🇹 Torino, Italy

Università degli Studi di Verona - A. O. - Istituti Ospitalieri di Verona- Div. di Ematologia - Policlinico G.B. Rossi; 🇮🇹 Verona, Italy

Università Cattolica del Sacro Cuore - Policlinico A. Gemelli; 🇮🇹 Roma, Italy