Inotuzumab Ozogamicin in Treating Patients With Relapsed or Refractory CD22 Positive Acute Lymphoblastic Leukemia

Study Overview
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Brief Summary
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This phase II trial studies how well inotuzumab ozogamicin works in treating patients with CD22 positive acute lymphoblastic leukemia that has come back or does not respond to treatment. Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a toxic agent called ozogamicin. Inotuzumab attaches to CD22 positive cancer cells in a targeted way and delivers ozogamicin to kill them.

Detailed Description
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PRIMARY OBJECTIVES: I. To evaluate the objective response rate of low dose of inotuzumab ozogamicin as measured by the hematologic remission rate (complete remission [CR] + CR with incomplete platelet recovery [CRp] + CR with incomplete bone marrow recovery [CRi]) in patients in first, second or later salvage setting. SECONDARY OBJECTIVES: I. To evaluate the overall safety profile and the efficacy; the efficacy is measured by the hematologic response rate (CR + CRi + PR), durations of response (DoR) and remission (DoR1), progression free survival (PFS), and overall survival (OS). OUTLINE: Patients receive inotuzumab ozogamicin intravenously (IV) over 1 hour on days 1, 8 and 15 of cycle 1 and on days 1 and 8 beginning cycle 2. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients whose disease gets worse after responding for 3 months, may be retreated for up to 6 additional cycles. Patients whose disease responds to treatment may receive up to 5 additional cycles.

Official Title
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Phase II Study of Low Dose Inotuzumab Ozogamicin in Patients With Relapsed and Refractory CD22 Positive Acute Lymphocytic Leukemia

Conditions
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CD22 Positive, Recurrent Acute Lymphoblastic Leukemia, Refractory Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Biological: Inotuzumab Ozogamicin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients at least 12 years of age Patients with a diagnosis of CD22-positive acute lymphoblastic leukemia (ALL) based on local immunophenotyping and histopathology who have: Refractory disease, defined as disease progression or no response while receiving their most recent prior anti-cancer therapy, Relapsed disease, defined as response to their most recent prior anti-cancer therapy with subsequent relapse Performance status of 0 to 3 Serum creatinine =< 2 x upper limit of normal (ULN) or estimated creatinine clearance >= 15 mL/min as calculated using the method standard for the institution Total serum bilirubin =< 1.5 x ULN unless the patient has documented Gilbert syndrome. If organ function abnormalities are considered due to tumor, total serum bilirubin must be =< 2 x ULN Aspartate and alanine aminotransferase (AST or ALT) =< 2.5 x ULN No active or co-existing malignancy requiring chemotherapy or radiation within 6 months Female subjects of childbearing potential should be willing to use effective methods birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year. Effective methods of birth control include birth control pills or injections, intrauterine devices (IUDs), or double-barrier methods (for example, a condom in combination with spermicide) Male subjects should agree to use an effective method of contraception starting with the first dose of study therapy through the duration of treatment Exclusion Criteria: Pregnant or nursing women Known to be human immunodeficiency virus (HIV)+ Philadelphia chromosome (Ph)+ ALL Active and uncontrolled disease/infection as judged by the treating physician Unable or unwilling to sign the consent form Prior allogeneic stem cell transplantation (ASCT) or other anti-CD22 immunotherapy within =< 4 months before first dose of study treatment Active central nervous system (CNS) or extramedullary disease unless approved by the principal investigator (PI) Monoclonal antibodies therapy within 2 weeks before study entry Radiotherapy and cancer chemotherapy (except for intrathecal chemotherapy, hydroxyurea, and cytarabine. Cytarabine and hydroxyurea are allowed to be used emergently in case of leukocytosis) or any investigational drug within 2 weeks before study entry Evidence or history of veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS)

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (inotuzumab ozogamicin)<br>Patients receive inotuzumab ozogamicin IV over 1 hour on days 1, 8 and 15 of cycle 1 and on days 1 and 8 beginning cycle 2. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients whose disease gets worse after responding for 3 months, may be retreated for up to 6 additional cycles. Patients whose disease responds to treatment may receive up to 5 additional cycles. | Biological: Inotuzumab Ozogamicin<br>* Given IV<br>* Other names: WAY-207294;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants to Achieve Complete Remission (CR) | Complete Remission (CR) is the normalization of the peripheral blood and bone marrow with </= 5% blasts with a granulocyte count of 1X10^9/L or above and a platelet count of >/= 100X10^9/L and absence of extramedullary disease. | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants With a Grade 3 or 4 Non-hematologic Adverse Event (AE) | For the purpose of toxicity monitoring, toxicities are defined as any treatment -related grade 3 or 4 non-hematologic AEs occurred any time during the trial.NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 utilized for adverse event reporting. | Up to 2 years | 
| Duration of Response | The date of Complete Response to the date of loss of response or last follow-up. | Up to 3 years | 
| Progression Free Survival | Time from date of treatment start until the date of first objective documentation of disease-relapse. | Up to 3 years | 
| Overall Survival | Time from date of treatment start until date of death due to any cause or last Follow-up. | Up to 3 years |