ALL2418: Feasibility and Effectiveness of Inotuzumab Ozogamicin in B-Cell Acute Lymphoblastic Leukemia

Sponsor

Gruppo Italiano Malattie EMatologiche dell'Adulto (Other)

Overall Status

Recruiting

CT.gov ID

NCT03610438

Collaborator

(none)

Enrollment

Locations

Arms

36.1

Anticipated Duration (Months)

2.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Lymphoid Leukemia	Drug: Inotuzumab Ozogamicin (IO) Drug: Inotuzumab Ozogamicin (IO)	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

76 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

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.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.

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Oct 30, 2019

Anticipated Primary Completion Date :

Nov 1, 2022

Anticipated Study Completion Date :

Nov 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 Cohort 1 will entroll 38 Ph+ patients	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.
Experimental: Cohort 2 Cohort 2 will enroll 38 Ph- patients	Drug: 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.

Arm

Intervention/Treatment

Experimental: Cohort 1

Cohort 1 will entroll 38 Ph+ patients

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.

Experimental: Cohort 2

Cohort 2 will enroll 38 Ph- patients

Drug: 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.

Outcome Measures

Primary Outcome Measures

Number of patients obtaining a negative Minimal Residual Disease (MRD) [Two years after study entry.]

Secondary Outcome Measures

Number of patients alive [Two years from start of treatment.]
Number of adverse events in MRD positive patients [Two years after study entry.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

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

Sponsors and Collaborators

Gruppo Italiano Malattie EMatologiche dell'Adulto

Investigators

Study Chair: Giovanni Martinelli, Istituto Scientifico Romagnoli per lo Studio e la Cura dei Tumori- IRST Italy
Study Director: Fabio Ciceri, Istituto S. Raffaele, Milan, Italy Giuseppe Saglio, Institute of Hematology, Ospedale Mauriziano, Turin, Italy