Title
A Phase II Study of Inotuzumab Ozogamicin Followed by Blinatumomab for PH-Negative cd22-Positive B-Lineage Acute Lymphoblastic Leukemia in Newly Diagnosed Older Adults or Adults With Relapsed or Refractory Disease

Description
Phase II study of inotuzumab ozogamicin followed by blinatumomab for Ph-negative, CD22-positive, B-lineage acute lymphoblastic leukemia in newly diagnosed older adults or adults with relapsed or refractory disease

Objective
The purpose of this study is to test the good and bad effects of the combination of drugs called inotuzumab ozogamicin and blinatumomab. The drug combination could cause your leukemia to go away and stop it from coming back, but it could also cause side effects. The study doctors hope to learn if the combination of study drugs will cause your cancer to go away and prevent your leukemia from coming back

Treatment inotuzumab ozogamicin through a vein on the first, eighth, and fifteenth day of each induction therapy course. The first induction therapy course of inotuzumab ozogamicin lasts 21 days. Based on your response to the first course of induction therapy you may or may not receive a second course of induction therapy with inotuzumab ozogamicin, and this second course will last 28 days. After completing all induction therapy, you will get blinatumomab through a vein without stopping through a pump that you can take away from the hospital; this is called a continuous infusion. You will get blinatumomab on the first through twenty-eighth and forty-third through seventieth days of each consolidation therapy course, and the first consolidation therapy course of blinatumomab lasts 84 days. Based on your response to the first course of consolidation therapy you may or may not receive a second course of consolidation therapy with blinatumomab, and this second course will last either 84 or 126 days

Key Eligibility
Cohort 1 and Cohort 2 Patients:

Ph-negative, CD22-positive precursor B-cell acute lymphoblastic leukemia

No active CNS leukemia

No known or suspected testicular involvement by leukemia

Not pregnant or nursing

ECOG Performance Status: 0-2

No unstable cardiac disease within 6 months of registration

No LVEF less than 45 percent or NYHA stage III or IV CHF

No history of clinically significant ventricular arrhythmia, unexplained non-vasovagal syncope, or chronic bradycardic states unless a permanent pacemaker has been implanted

Known HIV infection, hepatitis B virus (HBV), and/or history of hepatitis C virus (HCV) are allowed if they meet specified criteria

No history of clinically relevant neurologic disorder

No prior additional malignancy as defined by the protocol

No history of chronic liver disease including cirrhosis or SOS/VOD of the liver

No uncontrolled infection

Total bilirubin less than or equal to 1.5 x ULN

AST/ALT less than or equal to 2.5 x ULN

Calculated creatinine clearance greater than or equal to 40 mL/min

QTcF less than or equal to 470 msec

Cohort 1 Patients Only:

Age greater than or equal to 60 years

No prior therapy for ALL except a single dose of intrathecal chemotherapy, corticosteroids, hydroxyurea, and/or leukapheresis to reduce peripheral blast count and prevent ALL complications. Allowed therapy may be administered for no more than 14 days and must be completed greater than or equal to 24 hours before starting protocol therapy

No plan for allogeneic or autologous hematopoietic cell transplantation (HCT)

Cohort 2 Patients Only:

Age greater than or equal to 18 years

Relapsed or refractory disease in salvage 1 or 2

No isolated extramedullary relapse

Prior allogeneic HCT permitted. If prior allogeneic HCT, then patients must have completed transplantation greater than or equal to 4 months prior to registration, have no evidence of GvHD, and have completed immunosuppressive therapy greater than or equal to 30 days prior to registration

No prior treatment with CD22- or CD19-directed therapy. Prior treatment with rituximab must be completed greater than or equal to 14 days prior to registration. Prior treatment with other monoclonal antibodies must be completed greater than or equal to 6 weeks prior to registration

Prior treatment for ALL must be completed greater than or equal to 14 days prior to registration with the following exceptions: hydroxyurea, corticosteroids, 6-mercaptopurine, methotrexate, vincristine, and/or leukapheresis to reduce circulating absolute lymphoblast count to less than or equal to 10,000/uL or prevent complications related to ALL are allowed but must be completed greater than or equal to 24 hours prior to the start of protocol therapy.

Resolution of acute non-hematologic toxicities of prior therapy to CTCAE v5.0 grade less than or equal to 1

Peripheral blood absolute lymphoblast count less than or equal to 10,000/uL (treatment allowed as above to reduce blasts)

Applicable Disease Sites
Leukemia

Participating Institutions
UW Health University Hospital