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

B-cell Acute Lymphoblastic Leukemia Clinical Trial

— ALL-001  

Official title:

Phase I Study of Inotuzumab Ozogamicin With 3 and 4 Drug Augmented Berlin-Frankfurt-Münster (BFM) Re-Induction for Patients With Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia (B-ALL)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03962465
• Other study ID #: 21417
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: July 22, 2022
• Est. completion date: July 2026

Study information

• Verified date: August 2023
• Source: University of Virginia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In the proposed study, escalating doses of inotuzumab ozogamicin will be added to a standard pediatric inspired re-induction regimen and administered to patients 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.

Description:

Inotuzumab ozogamicin has been studied as a single agent in refractory and relapsed ALL. In the relapsed setting, inotuzumab ozogamicin has been shown to achieve complete remission (CR) in 81% of patients and minimal residual disease (MRD) negativity in 78% of patients who achieve CR. In the proposed study, escalating doses of inotuzumab ozogamicin will be added to a standard pediatric inspired re-induction regimen and administered to patients with relapsed or refractory B-cell ALL. Two re-induction regimens will be tested. The first regimen is a 3-drug regimen comprised of prednisone, vincristine, and daunorubicin. The second is a 4-drug regimen comprised of prednisone, vincristine, daunorubicin, and pegaspargase. Intrathecal methotrexate (IT-methotrexate) and intrathecal cytarabine (IT-ARA-C) will be included for central nervous system (CNS) prophylaxis with both the 3-drug and 4-drug regimens. We hypothesize that combining inotuzumab ozogamicin with these regimens is safe and will improve CR rates, successful transition to allo HCT, and overall survival in patients with relapsed or refractory B-ALL.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 36
• Est. completion date: July 2026
• Est. primary completion date: July 15, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 60 Years

Eligibility

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 will be defined based on the analysis completed for diagnostic purposes.

4. Male or female, aged 16-60 years

5. ECOG performance status of 0-2

6. Left ventricular ejection fraction = 50% measured by echocardiogram or MUGA

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

8. 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 (elevation exceeding this threshold of either AST OR ALT would not meet eligibility)

9. For females of reproductive potential: negative pregnancy test

10. 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

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

Exclusion Criteria:

1. 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)

2. Current or past history of pancreatitis

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

4. Known congestive heart failure

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

6. Presence of central nervous system (CNS) disease

7. Pregnancy or lactation

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

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

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

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

12. Active or uncontrolled infections

13. Abnormal baseline hepatic ultrasound (including Dopplers)

14. Prior allogeneic stem cell transplant

15. Prior use of inotuzumab ozogamicin

16. Known diagnosis of hemochromatosis with iron overload

17. Treatment with steroids or hydroxyurea for more than 7 days with each within the 2 weeks prior to registration -that is, each is allowed for up to 7 days

18. 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.

19. Philadelphia chromosome positive B-cell ALL

Related Conditions & MeSH terms

• B-cell Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Inotuzumab ozogamicin
By IV, given on days 12 and 19 Inotuzumab ozogamicin is approved as a single-agent in this population (patients with B-ALL) but adding it to these drug combinations has not been tested in humans
• Prednisone Pill
Taken daily days 1-28 by mouth
• Daunorubicin
By IV, given on days 1, 8, 15, and 22
• Vincristine
By IV, given on days 1, 8, 15, and 22
• Cytarabine
Intrathecal, administered on day 1 only
• Methotrexate
Intrathecal, administered on days 8 and 29
• Pegaspargase
By IV, given on day 4

Locations

Country	Name	City	State
United States	University of Virginia	Charlottesville	Virginia
United States	University of Wisconsin	Madison	Wisconsin
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	VCU Massey Cancer Center	Richmond	Virginia

Sponsors (5)

Lead Sponsor	Collaborator
University of Virginia	Pfizer, University of Wisconsin, Madison, Vanderbilt University, Virginia Commonwealth University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Characterization of Adverse Events (CTCAE version 5)	A characterization of all adverse events experienced by patients receiving these drug combinations. Also, any SAEs deemed related to study treatment, including veno-occlusive disease, will be captured at any time while the participant is on-study.	All adverse events occurring through 30 days following last dose of inotuzumab ozogamicin.
Primary	Dose-limiting toxicities	The number of dose-limiting toxicities will be used to determine the maximum tolerated dose combination for these combinations of drugs	From initiation of inotuzumab ozogamicin through 30 days following the last dose of inotuzumab ozogamicin
Primary	Informative course of treatment	Percent of patients that receive enough treatment to be informative to the study	For each participant, up to the 29 days of study treatment