Phase I Study of Inotuzumab With Augmented BFM Re-Induction for Younger Adults With Relapsed/Refractory B-cell ALL (ALL 001)

  • STATUS
    Recruiting
  • End date
    Nov 30, 2024
  • participants needed
    36
  • sponsor
    University of Virginia
Updated on 25 March 2022
remission
lymphoma
philadelphia chromosome
methotrexate
cytarabine
flow cytometry
vincristine
ejection fraction
prednisone
gilbert's syndrome
daunorubicin
pegaspargase
inotuzumab
prednisone pill

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.

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 younger adults 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 younger adults with relapsed or refractory B-ALL.

Details
Condition B-cell Acute Lymphoblastic Leukemia
Treatment methotrexate, cytarabine, vincristine, Pegaspargase, Daunorubicin, Inotuzumab Ozogamicin, Prednisone Pill
Clinical Study IdentifierNCT03962465
SponsorUniversity of Virginia
Last Modified on25 March 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Provision of signed and dated informed consent form
Stated willingness to comply with all study procedures and availability for the duration of the study
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
Body mass index (BMI) < 35 (BMI = weight in kg/(height in meters)^2)
Male or female, aged 18-55 years
ECOG performance status of 0-2
Left ventricular ejection fraction > 45% measured by echocardiogram or MUGA
Either relapsed following remission after initial induction therapy or refractory to induction therapy
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
For females of reproductive potential: negative pregnancy test
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
Agreement to adhere to Lifestyle Considerations throughout study duration and for 1 year following last study treatment

Exclusion Criteria

Requires concomitant therapeutic anticoagulation (e.g. warfarin, low molecular weight heparin, direct oral anticoagulant) or any medication included in the restricted concomitant medications
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)
Current or past history of pancreatitis
QT interval on electrocardiogram (ECG) > 0.45 by Framingham formula
Known congestive heart failure
Known allergy to asparaginase (only an exclusion criteria for participants enrolling in part 2)
Presence of central nervous system (CNS) disease
Pregnancy or lactation
Chronic liver disease including chronic active hepatitis and/or cirrhosis
Active Hepatitis B virus (HBV) by core antibody, surface antigen (HBsAg) or viral load
Active Hepatitis C virus (HCV) (positive antibody test confirmed by viral load if antibody test is positive)
Known history of infection with Human Immunodeficiency Virus (HIV)
Active or uncontrolled infections
Abnormal baseline hepatic ultrasound (including Dopplers)
Prior allogeneic stem cell transplant
Prior use of inotuzumab ozogamicin
Known diagnosis of hemochromatosis with iron overload
Prior CAR-T cell therapy
Treatment with steroids or hydroxyurea for more than 7 days within the 2 weeks prior to registration
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
Philadelphia chromosome positive B-cell ALL
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