B1931022: An Open-label, Randomized Phase 3 Study of Inotuzumab Ozogamicin Compared to a Defined Investigator's Choice in Adult Patients with Relapsed or Refractory CD22-Positive Acute Lymphoblastic Leukemia (ALL)

Summary

This multiple center, global, open-label, 2-arm randomized Phase 3 trial, designed to
compare the efficacy (in terms of CR/CRi) of inotuzumab ozogamicin (arm a) versus
investigator's choice of chemotherapy (arm B), will enroll 18 years old or older patients
with relapsed or refractory CD22-positive aLL in salvage 1 or 2. The trial will enroll at least
194 patients (97 per arm), and possibly up to 292 patients (See Section 9.1), over
approximately 26-36 months unless stopped earlier by the external Data Monitoring
Committee (e-DMC). To reflect the general relapsed/refractory aLL patient population, the
number of patients randomized due to receive salvage 2 will be capped at a third of the entire
trial population. Therefore, considering a total of 194 patients, only up to 64 (or up to 96 out of 292 patients) salvage 2 patients will be randomized into the study.

Patients in arm a will be treated with inotuzumab ozogamicin for a maximum dose of 1.8 mg/m2 per cycle with a
split dose regimen using weekly administrations.

Patients will receive 0.8 mg/m2 on week 1, followed by 0.5 mg/m2 on weeks 2 and 3 every 21-28 days cycle. in Cycle 2 and beyond, the inotuzumab ozogamicin dose administered on week 1 will be reduced to 0.5 mg/m2 in
patients achieving CR/CRi (for a total cycle dose of 1.5 mg/m2).

This global study will be run in approximately 190 sites.

Patients who achieve a response to treatment and who have a suitable donor may undergo stem-cell transplantation at the discretion of the investigator. These patients will remain in long-term follow-up phase for disease progression and survival.

Following discontinuation of treatment, patients will be followed for:
1. disease progression for up to 2 years from randomization, unless the patient
progressed during treatment;
2. potential VoD/SoS cases, irrespectively of grade or causality for up to 2 years from
randomization;
3. survival for up to 5 years or 2 years from randomization of the last patient, whichever
occurs first.

Participant Eligibility

1. Relapsed or refractory CD22-positive ALL ( >=5% marrow blasts, assessed by
morphology; i.e. M2 or M3 marrow) due to receive either salvage 1 or salvage 2
therapy and for which either arm of randomized study therapy offers a reasonable
treatment option;
2. Ph+ ALL patients must have failed treatment with at least 1 second or third generation
tyrosine kinase inhibitor;
3. Patients in Salvage 1 with late relapse should be deemed poor candidates for
reinduction with initial therapy;
4. Patients with lymphoblastic lymphoma and bone marrow involvement >=5%
lymphoblasts by morphologic assessment;
5. Age 18 years or older;
6. ECOG performance status 0-2;
7. Adequate liver function, including total serum bilirubin <=1.5 x ULN unless the patient
has documented Gilbert syndrome, and aspartate and alanine aminotransferase (AST
and ALT) <=2.5 x ULN. If organ function abnormalities are considered due to tumor,
total serum bilirubin must be <=2 x ULN and AST/ ALT <=2.5 x ULN;
8. Serum creatinine <=1.5 x upper limit of normal (ULN) or any serum creatinine level
associated with a measured or calculated creatinine clearance of >=40 mL/min;
9. Male and female patients of childbearing potential must agree to use a highly effective
method of contraception throughout the study and for a minimum of 90 days after the
last dose of assigned treatment. A patient is of childbearing potential if, in the opinion
of the investigator, he/she is biologically capable of having children and is sexually
active. Female patients who are not of childbearing potential (ie, meet at least one of
the following criteria):
a. Have undergone hysterectomy or bilateral oophorectomy; or
b. Have medically confirmed ovarian failure; or
c. Are medically confirmed to be post-menopausal (cessation of regular menses
for at least 12 consecutive months with no alternative pathological or
physiological cause.
10. Evidence of a personally signed and dated informed consent document indicating that
the patient has been informed of all pertinent aspects of the study;
11. Patients who are willing and able to comply with scheduled visits, treatment plan,
laboratory tests, and other study procedures.