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

Acute Lymphoid Leukemia Clinical Trial

— ALL2418  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03610438
• Other study ID #: ALL2418
• Secondary ID: 2018-003006-32
• Status: Recruiting
• Phase: Phase 2
• Start date: October 30, 2019
• Est. completion date: November 2022

Study information

• Verified date: December 2021
• Source: Gruppo Italiano Malattie EMatologiche dell'Adulto
• Contact: Paola Fazi
• Phone: +39 06 70390514
• Email: p.fazi[@]gimema.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 76
• Est. completion date: November 2022
• Est. primary completion date: November 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Lymphoid Leukemia
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Inotuzumab Ozogamicin (IO)
After course 1 MRD will be evaluated: - patients MRD negative will enter into short maintenance or long maintenance according to investigator choice. After 4 to 12 weeks in short maintenance patient will undergo SCT, otherwise, patients will enter long maintenance.
• Inotuzumab Ozogamicin (IO)
After course 2 MRD will be evaluated; patients MRD negative will enter into short maintenance or long maintenance by investigator choice. After 4 to 12 weeks in short maintenance patient will undergo SCT, otherwise, patients will enter long maintenance.

Locations

Country	Name	City	State
Italy	Aou Ospedali Riuniti "Umberto I - G.M. Lancisi - G. Salesi"- Ancona- Sod Clinica Ematologica	Ancona
Italy	Area Vasta N. 5 Ascoli Piceno - S. Benedetto Del Tronto, Presidio Ospedaliero Av5 Osp. Gen. Prov.Le "C.G.Mazzoni" - Uoc Ematologia	Ascoli Piceno
Italy	Asst Papa Giovanni Xxiii - Ospedale Di Bergamo - Sc Ematologia	Bergamo
Italy	Aou Di Bologna - Policlinico S. Orsola-Malpighi - Uoc Ematologia	Bologna
Italy	As Dell'Alto Adige, Ospedale Centrale Di Bolzano - Ematologia E Centro Trapianto Midollo Osseo	Bolzano
Italy	Asst Degli Spedali Civili Di Brescia - Uo Ematologia	Brescia
Italy	Aso S. Croce E Carle - Cuneo - Sc Ematologia	Cuneo
Italy	Irccs Aou San Martino - Genova - Uo Clinica Ematologica	Genova
Italy	Asl Lecce, Ospedale 'V. Fazzi' - Uo Ematologia	Lecce
Italy	I.R.S.T. Srl Irccs - Meldola - Sc Oncologia Medica	Meldola
Italy	Aulss 3 Serenissima, Ospedale Dell'Angelo - Mestre - Uo Ematologia	Mestre
Italy	Asst Grande Ospedale Metropolitano Niguarda - Milano - Sc Ematologia	Milano
Italy	Irccs Ospedale S. Raffaele - Milano - Uo Oncoematologia	Milano
Italy	Istituto Europeo Di Oncologia Irccs - Milano - Divisione Di Oncoematologia	Milano
Italy	Ao Di Rilievo Nazionale Antonio Cardarelli - Napoli - Uoc Ematologia Con Trapianto Di Midollo	Napoli
Italy	Ao Ospedali Riuniti Villa Sofia Cervello - Palermo - Uo Ematologia Con Utmo	Palermo
Italy	Fondazione Ircss Policlinico San Matteo - Pavia - Uo Ematologia	Pavia
Italy	Asl Pescara, Presidio Ospedaliero 'Spirito Santo' - Uoc Ematologia Clinica	Pescara
Italy	Grande Ospedale Metropolitano "Bianchi-Melacrino-Morelli" Po E. Morelli - Reggio Calabria - Uoc Ematologia	Reggio Calabria
Italy	Ausl Della Romagna, Ospedale "Infermi" - Rimini - Uo Ematologia	Rimini
Italy	Asl Roma 2, Ospedale S. Eugenio- Ospedale S.Eugenio - Uoc Ematologia	Roma
Italy	Università Degli Studi Di Roma "Sapienza" - Dipartimento Di Medicina Traslazionale E Di Precisione - U.O.C. Ematologia	Roma
Italy	Aou "San Giovanni Di Dio E Ruggi D'Aragona" - Salerno - Uoc Ematologia E Trapianti Di Cellule Staminali Emopoietiche	Salerno
Italy	Ente Ecclesiastico Casa Sollievo Della Sofferenza - San Giovanni Rotondo - Ematologia	San Giovanni Rotondo
Italy	Aou Senese - Uoc Ematologia E Trapianti	Siena
Italy	Aou Città Della Salute E Della Scienza, Ospedale S. Giovanni Battista Molinette - Torino - Sc Ematologia 2	Torino
Italy	Unità Operativa Di Ematologia - Presidio Ospedaliero Di Treviso - Azienda Ulss N.2 Marca Trevigiana	Treviso
Italy	Asui Di Udine - Presidio Ospedaliero "Santa Maria Della Misericordia" - Clinica Ematologica	Udine
Italy	Aou Integrata Di Verona, Policlinico G.B. Rossi - Uoc Ematologia	Verona
Italy	Aulss 8 Berica - Ospedale Di Vicenza - Uoc Ematologia	Vicenza

Sponsors (1)

Lead Sponsor	Collaborator
Gruppo Italiano Malattie EMatologiche dell'Adulto

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients obtaining a negative Minimal Residual Disease (MRD)		Two years after study entry.
Secondary	Number of patients alive		Two years from start of treatment.
Secondary	Number of adverse events in MRD positive patients		Two years after study entry.

External Links

•   GIMEMA Foundation website