Inotuzumab Ozogamicin Post-Transplant For Acute Lymphocytic Leukemia

Primary Objective Phase I: To define a post hematopoietic stem cell transplantation maximum
tolerated dose of inotuzumab Ozogamicin Phase II: To define the safety profile of inotuzumab
Ozogamicin therapy after allogeneic transplant.

Phase II: To determine the rate of veno-occlusive disease / sinusoidal obstruction syndrome
(VOD/SOS).

Secondary Objective(s)

1. To evaluate non-relapse mortality (NRM), relapse, relapse-related mortality and overall
survival (OS) at 1 year.

2. To determine the incidence of myeloid toxicity and secondary graft failure.

3. To determine if inotuzumab at these doses are effective at eradicating minimal residual
disease (MRD) in this cohort of patients.

Study Design This is a Phase I/II study of inotuzumab ozogamicin for the treatment of
patients who underwent allogeneic transplantation for ALL and have a high risk of relapse.
The Phase I portion of this study will be a 3/3 dose escalation trial with cohort expansion
at the maximum tolerated dose (MTD). Subjects will receive study treatment until relapse of
disease, unacceptable toxicity, 30 days after cycle 4, or death, whichever occurs first.

Phase I: Inotuzumab Ozogamicin Dosing Escalation Subjects will be assessed for safety and
tolerability (including adverse events, serious adverse events, and clinical/laboratory
assessments) using a continuous monitoring approach.

Phase II: Inotuzumab Ozogamicin Subjects will be assessed for safety and tolerability
(including adverse events, serious adverse events, and clinical/laboratory assessments) using
a continuous monitoring approach. In order to be included in the safety profile endpoint
review, subjects must have received at least of 1 cycle of treatment.

Phase I

Inclusion Criteria:

- Diagnosis of CD22-positive Acute Lymphoblastic Leukemia

- Patients who underwent an allogeneic hematopoietic stem cell transplantation from any
donor source for acute lymphocytic leukemia

- Patients who are between T+40 and T+100 after allogeneic transplantation. Patients
must receive their first dose of inotuzumab at or before T+100.

- Patients who have/are either:

- Transplanted in hematologic first complete remission with evidence of minimal
residual disease within 45 days of allogeneic transplantation

- Pre- or Post-Transplant Minimal Residual Disease defined by:

- Any detectable ALL (by flow cytometry, cytogenetics, or polymerase
chain reaction (PCR) techniques) as per clinical indication.

- In second or third complete remission at the time of allogeneic transplantation

- Treated with reduced intensity regimens

- Lymphoid blast crisis of CML

- Are relapsed or refractory to at least 1 line of chemotherapy

- Philadelphia-like ALL

- Patients who have evidence of donor chimerism after allogeneic transplantation.

- Philadelphia chromosome positive ALL must have failed at least 1 Tyrosine kinase
inhibitors (TKI)

- Eastern Cooperative Oncology Group (ECOG) Performance status ≤ 2

- Subjects must have the ability to understand and the willingness to sign a written
informed consent document.

- Subjects must have absolute neutrophil count (ANC) > 1,000 for 3 days and platelet
transfusion independence as defined as a platelet count > 20,000 for 7 days.

Phase II

Inclusion Criteria:

- Diagnosis of CD22-positive Acute Lymphoblastic Leukemia

- Patients who underwent an allogeneic hematopoietic stem cell transplantation from any
donor source for acute lymphocytic leukemia

- Patients who are between T+40 and T+100 after allogeneic transplantation

- Patients who have/are either:

- Transplanted in hematologic first complete remission with evidence of minimal
residual disease within 45 days of allogeneic transplantation

- Post-Transplant Minimal Residual Disease defined by:

- Any detectable ALL (by flow cytometry, cytogenetics, or PCR techniques)
as per clinical indication.

- In second or third complete remission at the time of allogeneic transplantation

- Treated with reduced intensity regimens

- Lymphoid blast crisis of CML

- Are relapsed or refractory to at least 1 line of chemotherapy

- Philadelphia-like ALL

- Patients who have ≥80% donor chimerism after allogeneic transplantation.

- Philadelphia chromosome positive ALL must have failed at least 1 TKI

- ECOG Performance status ≤ 2

- Subjects must have the ability to understand and the willingness to sign a written
informed consent document.

- Subjects must have ANC > 1,000 for 3 days and platelet transfusion independence as
defined as a platelet count > 20,000 for 7 days

Phase I/II

Exclusion Criteria:

- Patients with inadequate Organ Function as defined by:

- Creatinine clearance < 30ml/min

- Bilirubin ≥ 2 times institutional upper limit of normal

- Aspartate aminotransferase (AST SGOT) ≥ 2 times institutional upper limit of
normal

- Alanine aminotransferase (ALT SGPT) ≥ 2 times institutional upper limit of normal

- GVHD grade III or IV.

- Active acute or chronic graft-versus-host disease (GVHD) of the liver

- History of VOD

- Active malignancy

- Patients with uncontrolled inter-current illness including, but not limited to ongoing
or active infection, symptomatic congestive heart failure, unstable angina pectoris,
cardiac arrhythmia, or psychiatric illness/social situations that would limit
compliance with study requirements.

- Pregnant or breastfeeding women are excluded from this study

- Participation in any other investigational drug study or had exposure to any other
investigational agent, device, or procedure, within 21 days (or 5 half-lives,
whichever is greater)

- Any condition that would, in the investigator's judgment, interfere with full
participation in the study, including administration of study drug and attending
required study visits; pose a significant risk to the subject; or interfere with
interpretation of study data.

- Known allergies, hypersensitivity, or intolerance to any of the study medications,
excipients, or similar compounds