Clinical trial NCT03610438: Feasibility and Effectiveness of Inotuzumab Ozogamicin in B-Cell Acute Lymphoblastic Leukemia
Official title: A Phase IIA Study of Feasibility and Effectiveness of Inotuzumab Ozogamicin (IO) in Adult Patients With B-Cell Acute Lymphoblastic Leukemia With Positive Minimal Residual Disease Before Any Hematopoietic Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Acute Lymphoid Leukemia
Keywords: Acute Lymphoid Leukemia
Inotuzumab Ozogamicin
Lead sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto
Sponsor class: OTHER
First posted: 2018-08-01
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study is divided in two cohorts; cohort 1 will enroll 38 Ph+ patients, cohort 2 will enroll 38 Ph- patients, as defined with statistical analysis. The two cohorts will have the same treatment, with the exception of short term and long term maintenance.
Primary purpose: TREATMENT

Brief summary: This is a multi-center, phase 2A exploratory study of feasibility and effectiveness of Inotuzumab Ozagomicin in adult patients with Acute Lymphoid Leukemia (ALL) with positive minimal residual disease before any hematopoietic stem cell transplantation.

The study is divided in two cohorts; cohort 1 will enroll 38 Ph+ patients, cohort 2 will enroll 38 Ph- patients, as defined with statistical analysis. The two cohorts will have the same treatment, with the exception of short term and long term maintenance.


Eligibility criteria: Inclusion Criteria:

* Ph+ ALL with p190 or p210 detectable and measurable (at least 10-4 x10000 ABL) after at least 3 months of any therapy, or the failure of at least 2 TKI.
* Ph- ALL with detectable and measurable IG specific transcript after at least 2 courses of previous therapy.
* Age ≥ 18 years old.
* ECOG ≤ 2.

Exclusion Criteria:

* More than 5% of BM blasts.
* WHO performance status ≤ 50% (Karnofsky) or ≥ 3 (ECOG).
* Active HBV or HCV hepatitis, or AST/ALT ≥ 2.5 x ULN and bilirubine ≥ 1.5 x ULN.
* Evidence of liver fibrosis, portal hypertension or other clinically relevant liver abnormalities at screening liver ultrasonography.
* History of alcohol abuse.
* Burkitt lymphoma and active CNS leukemia. Patients with previuos neurological toxicitiy as well co-morbidity will be carefully evaluated for enrolment.
* Ongoing or active infections.
* Uncontrolled hypertriglyceridemia (triglycerides \>450 mg/dL). Clinically significant, uncontrolled, or active cardiovascular disease.
* Uncontrolled hypertension (diastolic blood pressure \>90 mm Hg; systolic \>140 mm Hg). Patients with hypertension should be under treatment on study entry to effect blood pressure control.
* Creatinine level \> 2.5mg/dl or Glomerular Filtration Rate (GFR) \< 20 ml/min or proteinuria \> 3.5 g/day.
* Documented inherited protrombotic disorders
* Patients who have received any investigational drug ≤ 4 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 with a history of another primary malignancy that is currently clinically significant or currently requires active intervention or with a life expectancy due to other malignancy \<6 months.
* Patients that have received Inotuzumab or Anti CD22 directed therapies before
* Patients with known hereditary coagulopathy
* Patient that received during their life diagnosis of VOD or had ongoing VOD
* Patients who are pregnant or breastfeeding and 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 induction therapy). Postmenopausal 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 4 months following discontinuation of study drugs.
* Patients unwilling or unable to comply with the protocol.

Primary outcomes:
measure: Number of patients obtaining a negative Minimal Residual Disease (MRD)
timeFrame: Two years after study entry.
Secondary outcomes:
measure: Number of patients alive
timeFrame: Two years from start of treatment.
measure: Number of adverse events in MRD positive patients
timeFrame: Two years after study entry.
Other outcomes:
Locations:
city: Ancona
country: Italy
facility: Aou Ospedali Riuniti "Umberto I - G.M. Lancisi - G. Salesi"- Ancona- Sod Clinica Ematologica
city: Ascoli Piceno
country: Italy
facility: Area Vasta N. 5 Ascoli Piceno - S. Benedetto Del Tronto, Presidio Ospedaliero Av5 Osp. Gen. Prov.Le "C.G.Mazzoni" - Uoc Ematologia
city: Bergamo
country: Italy
facility: Asst Papa Giovanni Xxiii - Ospedale Di Bergamo - Sc Ematologia
city: Bologna
country: Italy
facility: Aou Di Bologna - Policlinico S. Orsola-Malpighi - Uoc Ematologia
city: Bolzano
country: Italy
facility: As Dell'Alto Adige, Ospedale Centrale Di Bolzano - Ematologia E Centro Trapianto Midollo Osseo
city: Brescia
country: Italy
facility: Asst Degli Spedali Civili Di Brescia - Uo Ematologia
city: Cuneo
country: Italy
facility: Aso S. Croce E Carle - Cuneo - Sc Ematologia
city: Genova
country: Italy
facility: Irccs Aou San Martino - Genova - Uo Clinica Ematologica
city: Lecce
country: Italy
facility: Asl Lecce, Ospedale 'V. Fazzi' - Uo Ematologia
city: Meldola
country: Italy
facility: I.R.S.T. Srl Irccs - Meldola - Sc Oncologia Medica
city: Mestre
country: Italy
facility: Aulss 3 Serenissima, Ospedale Dell'Angelo - Mestre - Uo Ematologia
city: Milano
country: Italy
facility: Asst Grande Ospedale Metropolitano Niguarda - Milano - Sc Ematologia
city: Milano
country: Italy
facility: Irccs Ospedale S. Raffaele - Milano - Uo Oncoematologia
city: Milano
country: Italy
facility: Istituto Europeo Di Oncologia Irccs - Milano - Divisione Di Oncoematologia
city: Napoli
country: Italy
facility: Ao Di Rilievo Nazionale Antonio Cardarelli - Napoli - Uoc Ematologia Con Trapianto Di Midollo
city: Palermo
country: Italy
facility: Ao Ospedali Riuniti Villa Sofia Cervello - Palermo - Uo Ematologia Con Utmo
city: Pavia
country: Italy
facility: Fondazione Ircss Policlinico San Matteo - Pavia - Uo Ematologia
city: Pescara
country: Italy
facility: Asl Pescara, Presidio Ospedaliero 'Spirito Santo' - Uoc Ematologia Clinica
city: Reggio Calabria
country: Italy
facility: Grande Ospedale Metropolitano "Bianchi-Melacrino-Morelli" Po E. Morelli - Reggio Calabria - Uoc Ematologia
city: Rimini
country: Italy
facility: Ausl Della Romagna, Ospedale "Infermi" - Rimini - Uo Ematologia
city: Roma
country: Italy
facility: Asl Roma 2, Ospedale S. Eugenio- Ospedale S.Eugenio - Uoc Ematologia
city: Roma
country: Italy
facility: Università Degli Studi Di Roma "Sapienza" - Dipartimento Di Medicina Traslazionale E Di Precisione - U.O.C. Ematologia
city: Salerno
country: Italy
facility: Aou "San Giovanni Di Dio E Ruggi D'Aragona" - Salerno - Uoc Ematologia E Trapianti Di Cellule Staminali Emopoietiche
city: San Giovanni Rotondo
country: Italy
facility: Ente Ecclesiastico Casa Sollievo Della Sofferenza - San Giovanni Rotondo - Ematologia
city: Siena
country: Italy
facility: Aou Senese - Uoc Ematologia E Trapianti
city: Torino
country: Italy
facility: Aou Città Della Salute E Della Scienza, Ospedale S. Giovanni Battista Molinette - Torino - Sc Ematologia 2
city: Treviso
country: Italy
facility: Unità Operativa Di Ematologia - Presidio Ospedaliero Di Treviso - Azienda Ulss N.2 Marca Trevigiana
city: Udine
country: Italy
facility: Asui Di Udine - Presidio Ospedaliero "Santa Maria Della Misericordia" - Clinica Ematologica
city: Verona
country: Italy
facility: Aou Integrata Di Verona, Policlinico G.B. Rossi - Uoc Ematologia
city: Vicenza
country: Italy
facility: Aulss 8 Berica - Ospedale Di Vicenza - Uoc Ematologia
Study officials:
affiliation: Istituto Scientifico Romagnoli per lo Studio e la Cura dei Tumori- IRST Italy
name: Giovanni Martinelli
role: STUDY_CHAIR
affiliation: Istituto S. Raffaele, Milan, Italy Giuseppe Saglio, Institute of Hematology, Ospedale Mauriziano, Turin, Italy
name: Fabio Ciceri
role: STUDY_DIRECTOR
References: