LAL2317: Sequential Chemotherapy and Blinatumomab to Improve MRD Response and Survival in Acute Lymphoblastic Leukemia

Sponsor

Gruppo Italiano Malattie EMatologiche dell'Adulto (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03367299

Collaborator

(none)

149

Enrollment

Locations

Arm

67.8

Anticipated Duration (Months)

2.4

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The present study aims at analyzing the response to treatment of adult patients homogeneously treated with supportive care, chemotherapy and blinatumomab.

Condition or Disease	Intervention/Treatment	Phase
Acute Lymphoid Leukemia Philadelphia Chromosome-Negative B-Cell Precursor	Drug: Chemotherapy + Blinatumomab	Phase 2

Detailed Description

Eligible patients with CD19+ Ph- BCP ALL (Philadelphia-negative B-cell precursor acute lymphoblastic leukemia) will receive homogeneous supportive care, chemotherapy and blinatumomab immunotherapy, and will be homogeneously analyzed for response at prefixed time points from induction day 1. For risk-oriented therapy, patients in complete remission (CR) will be stratified by risk class according to the diagnostic characteristics and MRD (minimal residual disease) study results during early consolidation.

Study Design

Study Type:

Interventional

Actual Enrollment :

149 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

National Treatment Program With Sequential Chemotherapy and Blinatumomab to Improve Minimal Residual Disease Response and Survival in Philadelphia Chromosome-Negative B-Cell Precursor Adult Acute Lymphoblastic Leukemia

Actual Study Start Date :

Jun 8, 2018

Anticipated Primary Completion Date :

Feb 1, 2024

Anticipated Study Completion Date :

Feb 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Chemotherapy + Blinatumomab Treatment sequence consists of eight chemotherapy courses and two blinatumomab courses. Patients not in CR after chemotherapy course 2 will go off-study.	Drug: Chemotherapy + Blinatumomab Chemotherapy cycles are administered at 21-28 days intervals and each blinatumomab course is 28-day long.

Arm

Intervention/Treatment

Experimental: Chemotherapy + Blinatumomab

Treatment sequence consists of eight chemotherapy courses and two blinatumomab courses. Patients not in CR after chemotherapy course 2 will go off-study.

Drug: Chemotherapy + Blinatumomab

Chemotherapy cycles are administered at 21-28 days intervals and each blinatumomab course is 28-day long.

Outcome Measures

Primary Outcome Measures

Number of patients that obtain a negative Minimal Residual Disease (MRD) [At week 14 from study entry]

Secondary Outcome Measures

Number of patients in complete remission (CR) [At 32 months from study entry]
Number of patients that reach disease-free survial [At 32 months from study entry]
Number of patients that relapse [At 32 months from study entry]
Number of patients that dye due to treatment [At 32 months from study entry]
Treatment-related mortality
Number of serious adverse events [At 32 months from study entry]
Safety

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Signed written informed consent according to ICH/EU/GCP and national local laws.
Age 18-65 years.
A diagnosis of untreated Ph- CD19+ BCP ALL is required, either de novo or secondary to chemo-radiotherapy for another cancer. Pre-treatment with low-dose corticosteroids in patients presenting with hyperleukocytosis is allowed. Before enrolment and pre-phase is allowed only in patients presenting with severe, potentially life-threatening disease-related clinical symptoms. All diagnostic procedures need to be performed on freshly obtained bone marrow (BM) and peripheral blood (PB) samples.
Full cytological, cytochemical, immunophenotypic, cytogenetic and molecular disease characterization according to the EGIL and WHO classifications.
BM and PB sampling for MRD evaluations study. Detailed indications on patient registration, storage of representative diagnostic material and diagnostic work-up, including the shipping of samples for the diagnostic work-up and MRD follow-up studies are given in Appendix A.
An ECOG performance status 0-2, unless a performance of 3 is unequivocally caused by the disease itself, (and not by pre-existing comorbidities,) and is considered and/or documented to be reversible following the application of anti-leukemic therapy and appropriate supportive measures.

Exclusion Criteria:

Diagnosis of Burkitt's leukemia/lymphoma, CD19- BCP ALL, Ph+ ALL, T-ALL, lymphoblastic lymphoma (BM involvement by blast cells <25%).
Active CNS leukemia documented by diagnostic lumbar puncture on days -1 to -5 prior to the first blinatumomab administration, or any other clinical sign or symptom ascribable to symptomatic/documented CNS disease at time of each planned blinatumomab course.
Down's syndrome.
A pre-existing, uncontrolled pathology such as heart failure (congestive/ischemic, acute myocardial infarction within the past 3 months, untreatable arrhythmias, NYHA classes III and IV), severe liver disease with serum bilirubin >3 mg/dL and/or ALT >3 x upper normal limit (unless attributable to ALL), kidney function impairment with serum creatinine >2 mg/dL (unless attributable to ALL), and severe neuropsychiatric disorder that impairs the patient's ability to understand and sign the informed consent, or to cope with the intended treatment plan. N.B. For altered liver and kidney function tests, eligibility criteria can be reassessed at 24-96 hours, following the institution of adequate supportive measures.
Presence of serious, active, uncontrolled infections.
Pre-existing HIV positive serology (i.e. already known before enrolment). If HIV positivity is detected after enrolment, the patient is put off study.
A history of cancer that is not in a remission phase following surgery and/or radiotherapy and/or chemotherapy, with a life expectancy <1 year.
Pregnancy declared by the patient, unless a decision is taken with the patient to induce a therapeutic abortion in order to carry on with the ALL therapy. A pregnancy test is performed at diagnosis, but does not preclude the enrolment into study. Fertile patients will be advised to adopt contraceptive methods while on treatment.

Contacts and Locations

Locations

	Site	City	Country
1	AOU Ospedali Riuniti Umberto I - G.M. LANCISI - G. SALESI	Ancona	Italy
2	U.O.C. Ematologia e Terapia Cellulare - Ospedale "C. e G. Mazzoni" di Ascoli Piceno	Ascoli Piceno	Italy
3	Az.Ospedaliera S.G.Moscati	Avellino	Italy
4	UO Ematologia con trapianto-Università degli Studi di Bari Aldo Moro	Bari	Italy
5	UOC di Ematologia - Istituto Tumori - Giovanni Paolo II	Bari	Italy
6	UOC Ematologia Ospedale " Monsignor Raffaele Dimiccoli"	Barletta	Italy
7	Azienda Ospedaliera - Papa Giovanni XXIII	Bergamo	Italy
8	Istituto di Ematologia "Lorenzo e A. Seragnoli" - Policlinico S. Orsola - Malpighi	Bologna	Italy
9	Comprensorio Sanitario di Bolzano - Azienda Sanitaria dell'Alto Adige - Ematologia e Centro TMO - Ospedale S.Maurizio	Bolzano	Italy
10	Spedali Civili - Brescia - Azienda Ospedaliera - U.O. Ematologia	Brescia	Italy
11	Divisione di Ematologia Ospedale A. Perrino	Brindisi	Italy
12	ASL N.8 - Ospedale "A. Businco" - Struttura Complessa di Ematologia e CTMO	Cagliari	Italy
13	Università di Catania - Cattedra di Ematologia - Ospedale "Ferrarotto"	Catania	Italy
14	S.C. Ematologia ASO S. Croce e Carle	Cuneo	Italy
15	Unità di Ricerca e di Malattie del sangue - Ematologia San Luca Vecchio	Firenze	Italy
16	IRCCS_AOU San Martino-IST-Ematologia 1-Monoblocco 11°piano- lato ponente	Genova	Italy
17	UOC di Ematologia con trapianto Ospedale S. Maria Goretti	Latina	Italy
18	ASL Le/1 P.O. Vito Fazzi - U.O. di Ematologia ed UTIE	Lecce	Italy
19	Istituto Scientifico Romagnoli per lo Studio e la Cura dei Tumori- IRST	Meldola	Italy
20	A.O.U. - Policlinico G. Martino Messina Oncologia Medica - U.O.C. Ematologia	Messina	Italy
21	U.O. di Ematologia- Ospedale dell'Angelo - Mestre	Mestre	Italy
22	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico UOC Oncoematologia	Milano	Italy
23	Ospedale Niguarda " Ca Granda" - SC Ematologia	Milano	Italy
24	U.O. Ematologia e Trapianto di MIdollo - Ist.Scientifico Ospedale San Raffaele	Milano	Italy
25	UO Ematologia - AOU Policlinico di Modena	Modena	Italy
26	Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli"	Napoli	Italy
27	Università degli Studi di Napoli "Federico II" - Facoltà di Medicina e Chirurgia	Napoli	Italy
28	S.C.D.U. Ematologia - Università del Piemonte Orientale Amedeo Avogadro	Novara	Italy
29	U.O. CTMO Ematologia - Osp. S.Francesco	Nuoro	Italy
30	S.C.D.U.Medicina Interna a indirizzo ematologico	Orbassano	Italy
31	Università degli Studi di Padova - Ematologia ed Immunologia Clinica	Padova	Italy
32	Oncoematologia -plesso ospedaliero "A. Tortora" di Pagani	Pagani	Italy
33	Ospedali Riuniti "Villa Sofia-Cervello"	Palermo	Italy
34	U.O. di Ematologia con trapianto - Centro di Riferimento Regionale per le coagulopatie rare nel bambino e nell'adulto - A.U. Policlinico "Paolo Giaccone"	Palermo	Italy
35	Day Hospital dell'U.O.C di Ematologia e CTMO Padiglione 1	Parma	Italy
36	S.C. Ematologia - Fondazione IRCCS Policlinico S. Matteo	Pavia	Italy
37	Sezione di Ematologia ed Immunologia Clinica - Ospedale S.Maria della Misericordia	Perugia	Italy
38	U.O. Ematologia Clinica - Azienda USL di Pescara	Pescara	Italy
39	U.O. Ematologia - AUSL Ospedale G. da Saliceto	Piacenza	Italy
40	Dipartimento Oncologico - Ospedale S.Maria delle Croci	Ravenna	Italy
41	Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli"	Reggio Calabria	Italy
42	Ospedale "Infermi"	Rimini	Italy
43	Az. Ospedaliera "Sant' Andrea"-Università la Sapienza II Facoltà di Medicina e Chirurgia	Roma	Italy
44	Complesso Ospedaliero S. Giovanni Addolorata	Roma	Italy
45	Padiglione Cesalpino - I piano - Divisione di Ematologia - Ospedale S. Camillo	Roma	Italy
46	S.C. di Ematologia e Trapianti - I.F.O. Istituto Nazionale Tumori Regina Elena	Roma	Italy
47	U.O.C. Ematologia - Ospedale S. Eugenio	Roma	Italy
48	Università Cattolica del Sacro Cuore - Policlinico A. Gemelli	Roma	Italy
49	Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari - Divisione di Ematologia	Roma	Italy
50	Università degli Studi - Policlinico di Tor Vergata	Roma	Italy
51	Sezione di Ematologia Cancer Center Humanitas	Rozzano	Italy
52	UOC di Ematologia - AOU San Giovanni di Dio e Ruggi D'Aragona	Salerno	Italy
53	Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza	San Giovanni Rotondo	Italy
54	U.O.C. Ematologia - A.O. Senese - Policlinico " Le Scotte"	Siena	Italy
55	U.O.C. di Ematologia - A.O. " SS Annunziata" - P.O. S.G. Moscati	Taranto	Italy
56	Divisione di Ematologia dell'Università di Torino - "Città della Salute e della Scienza"	Torino	Italy
57	Ematologia e Terapie Cellulari- A.S.O. Ordine Mauriziano, P.O. Umberto I-Ospedale	Torino	Italy
58	S.C. Ematologia 2 A.O. Città della Salute e della Scienza di Torino San Giovanni Battista	Torino	Italy
59	Struttura Complessa Ematologia - Azienda Ospedaliera Universitaria Integrata-Ospedale Maggiore	Trieste	Italy
60	Clinica Ematologica-Centro Trapianti e Terapie cellulari AOU,	Udine	Italy
61	Istituti Ospitalieri di Verona- Div. di Ematologia - Policlinico G.B. Rossi	Verona	Italy
62	ULSS N.6 Osp. S. Bortolo	Vicenza	Italy

Sponsors and Collaborators

Gruppo Italiano Malattie EMatologiche dell'Adulto

Investigators

Study Chair: Renato Bassan, Azienda ULSS 12 "Veneziana" U.O. Ematologia Direttore Renato Bassan
Study Director: Roberto Foà, Policlinico Umberto I, Hematology Department.
Study Director: Alessandro Rambaldi, Ospedale di Bergamo