Description:
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.
Title
- Brief Title: Phase I Study of Inotuzumab With Augmented BFM Re-Induction for Younger Adults With Relapsed/Refractory B-cell ALL
- Official Title: Phase I Study of Inotuzumab Ozogamicin With 3 and 4 Drug Augmented Berlin-Frankfurt-Münster (BFM) Re-Induction for Younger Adults Ages 18-55 With Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia (B-ALL)
Clinical Trial IDs
- ORG STUDY ID:
21417
- NCT ID:
NCT03962465
Conditions
- B-cell Acute Lymphoblastic Leukemia
Interventions
Drug | Synonyms | Arms |
---|
Inotuzumab ozogamicin | Besponsa | 3-drug re-induction regimen with inotuzumab |
Prednisone Pill | Deltasone | 3-drug re-induction regimen with inotuzumab |
Daunorubicin | Cerubidine, daunomycin, rubidomycin | 3-drug re-induction regimen with inotuzumab |
Vincristine | Oncovin, Vincasar, Leurocristine | 3-drug re-induction regimen with inotuzumab |
Cytarabine | Ara-C, Cytosar-U | 3-drug re-induction regimen with inotuzumab |
Methotrexate | Otrexup, Rasuvo, Rheumatrex, Trexall, MTX, Amethopterin | 3-drug re-induction regimen with inotuzumab |
Pegaspargase | Oncospar | 4-drug re-induction regimen with inotuzumab |
Purpose
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.
Detailed 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.
Trial Arms
Name | Type | Description | Interventions |
---|
3-drug re-induction regimen with inotuzumab | Experimental | One cycle of a 3-drug regimen comprised of standard doses of prednisone, vincristine, and daunorubicin with inotuzumab ozogamicin at a reduced dose.
Intrathecal methotrexate (IT-methotrexate) and intrathecal cytarabine (IT-Ara-C) will be included for CNS prophylaxis.
IV inotuzumab ozogamicin will be given at a reduced dose (may vary from a total cycle dose of 0.4 mg/m^2 to 0.9 mg/m^2) | - Inotuzumab ozogamicin
- Prednisone Pill
- Daunorubicin
- Vincristine
- Cytarabine
- Methotrexate
|
4-drug re-induction regimen with inotuzumab | Experimental | One cycle of a 4-drug regimen comprised of standard doses of prednisone, vincristine, daunorubicin, and pegaspargase with inotuzumab ozogamicin at a reduced dose.
Intrathecal methotrexate (IT-methotrexate) and intrathecal cytarabine (IT-Ara-C) will be included for CNS prophylaxis.
IV inotuzumab ozogamicin will be given at a reduced dose (may vary from a total cycle dose of 0.4 mg/m^2 to 0.9 mg/m^2) | - Inotuzumab ozogamicin
- Prednisone Pill
- Daunorubicin
- Vincristine
- Cytarabine
- Methotrexate
- Pegaspargase
|
Eligibility 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
Maximum Eligible Age: | 55 Years |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Characterization of Adverse Events (CTCAE version 5) |
Time Frame: | All adverse events occurring through 30 days following last dose of inotuzumab ozogamicin. |
Safety Issue: | |
Description: | 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. |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | University of Virginia |
Last Updated
September 11, 2020