Chemotherapy-free treatment for Ph+ Acute Lymphoblastic Leukemia using Inotuzumab Ozogamicin

A Phase II Study of a Chemotherapy-Free Induction Regimen for Ph+ Acute Lymphoblastic Leukemia (ALL) Incorporating Inotuzumab Ozogamicin (InO)

This study is testing if adding a new drug called inotuzumab ozogamicin to standard treatment can help adults with newly diagnosed Ph+ acute lymphoblastic leukemia get better faster and more completely.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 25 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Chicago (other)
• Drugs / interventions: Inotuzumab, radiation
• Locations: 1 site (Chicago, Illinois)
• Trial ID: NCT04747912 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the addition of inotuzumab ozogamicin (InO) to the standard induction treatment for patients with newly diagnosed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). The goal is to determine if this combination can lead to quicker and more complete molecular remission of the disease. Participants must be 18 years or older and have specific criteria related to their leukemia diagnosis and health status. The study aims to gather data on the effectiveness of InO in this patient population who have not yet received treatment.

Who should consider this trial

Good fit: Ideal candidates are newly diagnosed adults with Ph+ B-cell acute lymphoblastic leukemia who meet specific clinical criteria.

Not a fit: Patients who have previously received treatment for acute lymphoblastic leukemia or do not express CD22 on their blasts may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a more effective treatment option for patients with Ph+ acute lymphoblastic leukemia, potentially leading to faster remission.

How similar studies have performed: Other studies have shown promise with similar approaches, but this specific combination is being evaluated for the first time in this context.

Eligibility criteria

Inclusion Criteria:

1. Must be a newly diagnosed and untreated patient with Ph+ B-cell Acute Lymphoblastic Leukemia and CD22 expression on ≥20% of blasts.
2. 18 years old or older.
3. Bone marrow involvement with ≥20% lymphoblasts and demonstration of BCR-ABL1 via fluorescence in situ hybridization (FISH) studies or PCR-based testing. Patients with \>1000/mm3 lymphoblasts in the peripheral blood that cannot undergo bone marrow biopsy and aspiration due to clinical condition are also eligible.
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
5. Adequate organ function as confirmed by clinical/medical record.
6. Patients must be at least 2 weeks from major surgery, radiation therapy, or participation in other investigational trials, and must have recovered from clinically significant toxicities related to these prior treatments.
7. Patients must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee/Institutional Review Board prior to starting any screening or study-specific procedures.
8. Females of childbearing potential will use effective contraception during treatment with InO and for at least 8 months after the last dose. Males with female partners of reproductive potential will use effective contraception during treatment with Inotuzumab Ozogamicin and for at least 5 months after the last dose. A patient is of childbearing potential if, in the opinion of the treating investigator, he/she is biologically capable of having children and is sexually active. Female patients who are not of childbearing potential (ie, meet at least one of the following criteria):

   a. Have undergone hysterectomy or bilateral oophorectomy; or have medically confirmed ovarian failure; or are medically confirmed to be post-menopausal (cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause).
9. Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria:

1. Isolated extramedullary disease.
2. Burkitt's or mixed-lineage leukemia.
3. Active central nervous system (CNS) leukemia.
4. Any prior therapy for ALL except for limited treatment (≤ 7 days) with corticosteroids or hydroxyurea and a single dose of intrathecal therapy. Patients who are being treated with chronic steroids for other reasons (eg, asthma, autoimmune disorders) are eligible.
5. Current or chronic hepatitis B or C infection as evidenced by hepatitis B surface antigen and anti-hepatitis C antibody positivity, respectively, or known seropositivity for human immunodeficiency virus (HIV). HIV testing may need to be performed in accordance with local regulations or local practice. Patients with HIV but an undetectable viral load are eligible for enrollment
6. Major surgery within ≤ 2 weeks before randomization.
7. Unstable or severe uncontrolled medical condition (eg, unstable cardiac function or unstable pulmonary condition.
8. Concurrent active malignancy other than non-melanoma skin cancer, carcinoma in situ of the cervix, or localized prostate cancer that has been definitely treated with radiation or surgery. Patients with previous malignancies are eligible provided that they have been disease free for ≥2 years or are not currently requiring treatment.
9. Uncontrolled cardiac disease.
10. QTcF \> 500 msec (based on the average of 3 consecutive ECGs).
11. History of chronic liver disease (eg, cirrhosis) or suspected alcohol abuse.
12. History of hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS).
13. Evidence of uncontrolled current serious active infection including sepsis, bacteremia, fungemia, or patients with a recent history (within 4 months) of deep tissue infections such as fasciitis or osteomyelitis.
14. Medications known to predispose to Torsades de Pointes are prohibited throughout the treatment period of the study.
15. Pregnant females; breastfeeding females; males with female partners of reproductive potential and females of childbearing potential not using highly effective contraception or not agreeing to continue highly effective contraception for a minimum of 5 months after the last dose of investigational product if male and 8 months after the last dose of investigational product if female.
16. Patients who are investigational site staff members or relatives of those site staff members or patients who are Pfizer employees directly involved in the conduct of the trial.
17. Participation in other investigational studies during active treatment phase.
18. Other severe acute, chronic medical, psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the Study Lead Principal Investigator, would make the patient inappropriate for entry into this study.

Where this trial is running

Chicago, Illinois

• University of Chicago Medical Center — Chicago, Illinois, United States (RECRUITING)

Study contacts

• Principal investigator: Wendy Stock, MD — University of Chicago
• Study coordinator: Cancer Clinical Trials Office

Conditions: Lymphoblastic Leukemia, Acute Lymphoblastic Leukemia, ph+ Acute Lymphoblastic Leukemia, leukemia