Phase I Study of Inotuzumab With Augmented BFM Re-Induction for Younger Adults With Relapsed/Refractory B-cell ALL

• Status: Recruiting
• Trial end date: 2025-11-30
• Target enrollment: 0
• Participant gender: All

Summary

In the proposed study, escalating doses of inotuzumab ozogamicin will be added to a standard pediatric inspired re-induction regimen and administered to younger adults with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). Two re-induction regimens will be tested (one without pegaspargase and one including pegaspargase) and participants will be followed for disease status, allogeneic hematopoietic cell transplant (allo HCT), veno-occlusive disease following allo HCT, and overall survival.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Virginia
• Collaborators: Pfizer; University of Wisconsin, Madison; Vanderbilt University; Virginia Commonwealth University
• Treatments: Cytarabine; Daunorubicin; Inotuzumab Ozogamicin; Methotrexate; Pegaspargase; Prednisone; Vincristine

Criteria

Inclusion Criteria:

1. Provision of signed and dated informed consent form

2. Stated willingness to comply with all study procedures and availability for the duration of the study

3. Diagnosed with CD-22 positive* B-cell Acute Lymphoblastic Leukemia or B-cell Lymphoblastic Lymphoma (Philadelphia chromosome negative) * For the purposes of this study, CD-22 positive is defined as at least 60% positive by flow cytometry or immunohistochemistry.

4. Body mass index (BMI) < 35 (BMI = weight in kg/(height in meters)^2)

5. Male or female, aged 18-55 years

6. ECOG performance status of 0-2

7. Left ventricular ejection fraction > 45% measured by echocardiogram or MUGA

8. Either relapsed following remission after initial induction therapy or refractory to induction therapy

9. Adequate organ function, including serum creatinine ≤ 1.6 mg/dL or creatinine clearance < 50 ml/min by Cockgroft-Gault formula, bilirubin ≤ 1.5 mg/dL (except in patients with Gilbert's disease), AST, ALT and alkaline phosphatase ≤ 3 x upper limit of normal

10. For females of reproductive potential: negative pregnancy test

11. For females and males of reproductive potential: agreement to use adequate contraception during study participation and for an additional 1 year after the end of study treatment

12. Agreement to adhere to Lifestyle Considerations throughout study duration and for 1 year following last study treatment.

Exclusion Criteria:

1. Requires concomitant therapeutic anticoagulation (e.g. warfarin, low molecular weight heparin, direct oral anticoagulant) or any medication included in the restricted concomitant medications

2. Past receipt of a total of ≥ 300 mg/m^2 doxorubicin equivalents (600 mg/m^2 daunorubicin, 60 mg/m^2 idarubicin, 75 mg/m^2 mitoxantrone)

3. Current or past history of pancreatitis

4. QT interval on electrocardiogram (ECG) > 0.45 by Framingham formula

5. Known congestive heart failure

6. Known allergy to asparaginase (only an exclusion criteria for participants enrolling in part 2)

7. Presence of central nervous system (CNS) disease

8. Pregnancy or lactation

9. Chronic liver disease including chronic active hepatitis and/or cirrhosis

10. Active Hepatitis B virus (HBV) by core antibody, surface antigen (HBsAg) or viral load

11. Active Hepatitis C virus (HCV) (positive antibody test confirmed by viral load if antibody test is positive)

12. Known history of infection with Human Immunodeficiency Virus (HIV)

13. Active or uncontrolled infections

14. Abnormal baseline hepatic ultrasound (including Dopplers)

15. Prior allogeneic stem cell transplant

16. Prior use of inotuzumab ozogamicin

17. Known diagnosis of hemochromatosis with iron overload

18. Prior CAR-T cell therapy

19. Treatment with steroids or hydroxyurea for more than 7 days within the 2 weeks prior to registration

20. Gastrointestinal tract disease causing the inability to take oral medication, malabsorption syndrome, a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease, or inability to swallow medications.

21. Philadelphia chromosome positive B-cell ALL