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Feasibility and Effectiveness of Inotuzumab Ozogamicin in B-Cell Acute Lymphoblastic Leukemia

Phase 2
Conditions
Acute Lymphoid Leukemia
Interventions
Drug: Inotuzumab Ozogamicin (IO)
Registration Number
NCT03610438
Lead Sponsor
Gruppo Italiano Malattie EMatologiche dell'Adulto
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
76
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Cohort 1Inotuzumab Ozogamicin (IO)Cohort 1 will entroll 38 Ph+ patients
Cohort 2Inotuzumab Ozogamicin (IO)Cohort 2 will enroll 38 Ph- patients
Primary Outcome Measures
NameTimeMethod
Number of patients obtaining a negative Minimal Residual Disease (MRD)Two years after study entry.
Secondary Outcome Measures
NameTimeMethod
Number of adverse events in MRD positive patientsTwo years after study entry.
Number of patients aliveTwo years from start of treatment.

Trial Locations

Locations (30)

I.R.S.T. Srl Irccs - Meldola - Sc Oncologia Medica

🇮🇹

Meldola, Italy

Asst Grande Ospedale Metropolitano Niguarda - Milano - Sc Ematologia

🇮🇹

Milano, Italy

Istituto Europeo Di Oncologia Irccs - Milano - Divisione Di Oncoematologia

🇮🇹

Milano, Italy

Grande Ospedale Metropolitano "Bianchi-Melacrino-Morelli" Po E. Morelli - Reggio Calabria - Uoc Ematologia

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Reggio Calabria, Italy

Aou Di Bologna - Policlinico S. Orsola-Malpighi - Uoc Ematologia

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Bologna, Italy

Aso S. Croce E Carle - Cuneo - Sc Ematologia

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Cuneo, Italy

Asl Lecce, Ospedale 'V. Fazzi' - Uo Ematologia

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Lecce, Italy

Asst Degli Spedali Civili Di Brescia - Uo Ematologia

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Brescia, Italy

Aulss 3 Serenissima, Ospedale Dell'Angelo - Mestre - Uo Ematologia

🇮🇹

Mestre, Italy

Ao Di Rilievo Nazionale Antonio Cardarelli - Napoli - Uoc Ematologia Con Trapianto Di Midollo

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Napoli, Italy

Aou Integrata Di Verona, Policlinico G.B. Rossi - Uoc Ematologia

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Verona, Italy

Irccs Ospedale S. Raffaele - Milano - Uo Oncoematologia

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Milano, Italy

Ao Ospedali Riuniti Villa Sofia Cervello - Palermo - Uo Ematologia Con Utmo

🇮🇹

Palermo, Italy

Fondazione Ircss Policlinico San Matteo - Pavia - Uo Ematologia

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Pavia, Italy

Ausl Della Romagna, Ospedale "Infermi" - Rimini - Uo Ematologia

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Rimini, Italy

Asl Roma 2, Ospedale S. Eugenio- Ospedale S.Eugenio - Uoc Ematologia

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Roma, Italy

Università Degli Studi Di Roma "Sapienza" - Dipartimento Di Medicina Traslazionale E Di Precisione - U.O.C. Ematologia

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Roma, Italy

Aou "San Giovanni Di Dio E Ruggi D'Aragona" - Salerno - Uoc Ematologia E Trapianti Di Cellule Staminali Emopoietiche

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Salerno, Italy

Aou Senese - Uoc Ematologia E Trapianti

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Siena, Italy

Aou Città Della Salute E Della Scienza, Ospedale S. Giovanni Battista Molinette - Torino - Sc Ematologia 2

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Torino, Italy

Unità Operativa Di Ematologia - Presidio Ospedaliero Di Treviso - Azienda Ulss N.2 Marca Trevigiana

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Treviso, Italy

Asui Di Udine - Presidio Ospedaliero "Santa Maria Della Misericordia" - Clinica Ematologica

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Udine, Italy

Aulss 8 Berica - Ospedale Di Vicenza - Uoc Ematologia

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Vicenza, Italy

Aou Ospedali Riuniti "Umberto I - G.M. Lancisi - G. Salesi"- Ancona- Sod Clinica Ematologica

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Ancona, Italy

Asst Papa Giovanni Xxiii - Ospedale Di Bergamo - Sc Ematologia

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Bergamo, Italy

Area Vasta N. 5 Ascoli Piceno - S. Benedetto Del Tronto, Presidio Ospedaliero Av5 Osp. Gen. Prov.Le "C.G.Mazzoni" - Uoc Ematologia

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Ascoli Piceno, Italy

As Dell'Alto Adige, Ospedale Centrale Di Bolzano - Ematologia E Centro Trapianto Midollo Osseo

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Bolzano, Italy

Irccs Aou San Martino - Genova - Uo Clinica Ematologica

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Genova, Italy

Asl Pescara, Presidio Ospedaliero 'Spirito Santo' - Uoc Ematologia Clinica

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Pescara, Italy

Ente Ecclesiastico Casa Sollievo Della Sofferenza - San Giovanni Rotondo - Ematologia

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San Giovanni Rotondo, Italy

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