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Trial record 20 of 25 for:    "Acute Lymphocytic Leukemia" | "inotuzumab ozogamicin"

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

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ClinicalTrials.gov Identifier: NCT03962465
Recruitment Status : Not yet recruiting
First Posted : May 24, 2019
Last Update Posted : May 24, 2019
Sponsor:
Collaborators:
Pfizer
Vanderbilt University
University of Wisconsin, Madison
Virginia Commonwealth University
Information provided by (Responsible Party):
Michael Douvas, MD, University of Virginia

Brief 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.

Condition or disease Intervention/treatment Phase
B-cell Acute Lymphoblastic Leukemia Drug: Inotuzumab ozogamicin Drug: Prednisone Pill Drug: Daunorubicin Drug: Vincristine Drug: Cytarabine Drug: Methotrexate Drug: Pegaspargase Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description: This is an early-phase study evaluating the safety of inotuzumab ozogamicin administered in combination with a 3-drug and 4-drug re-induction regimen in participants with relapsed or refractory B-ALL. The trial is planned to first determine the maximum tolerated dose (MTD) of the 3-drug re-induction regimen in Part 1 and then to determine the MTD of the 4-drug re-induction regimen (including pegaspargase) in Part 2.
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Estimated Study Start Date : July 2019
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : July 2025


Arm Intervention/treatment
Experimental: 3-drug re-induction regimen with inotuzumab

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)

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
Other Name: Besponsa

Drug: Prednisone Pill
Taken daily days 1-28 by mouth
Other Name: Deltasone

Drug: Daunorubicin
By IV, given on days 1, 8, 15, and 22
Other Names:
  • Cerubidine
  • daunomycin
  • rubidomycin

Drug: Vincristine
By IV, given on days 1, 8, 15, and 22
Other Names:
  • Oncovin
  • Vincasar
  • Leurocristine

Drug: Cytarabine
Intrathecal, administered on day 1 only
Other Names:
  • Ara-C
  • Cytosar-U

Drug: Methotrexate
Intrathecal, administered on days 8 and 29
Other Names:
  • Otrexup
  • Rasuvo
  • Rheumatrex
  • Trexall
  • MTX
  • Amethopterin

Experimental: 4-drug re-induction regimen with inotuzumab

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)

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
Other Name: Besponsa

Drug: Prednisone Pill
Taken daily days 1-28 by mouth
Other Name: Deltasone

Drug: Daunorubicin
By IV, given on days 1, 8, 15, and 22
Other Names:
  • Cerubidine
  • daunomycin
  • rubidomycin

Drug: Vincristine
By IV, given on days 1, 8, 15, and 22
Other Names:
  • Oncovin
  • Vincasar
  • Leurocristine

Drug: Cytarabine
Intrathecal, administered on day 1 only
Other Names:
  • Ara-C
  • Cytosar-U

Drug: Methotrexate
Intrathecal, administered on days 8 and 29
Other Names:
  • Otrexup
  • Rasuvo
  • Rheumatrex
  • Trexall
  • MTX
  • Amethopterin

Drug: Pegaspargase
By IV, given on day 4
Other Name: Oncospar




Primary Outcome Measures :
  1. Characterization of Adverse Events (CTCAE version 5) [ Time Frame: All adverse events occurring through 30 days following last dose of inotuzumab ozogamicin. ]
    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.

  2. Dose-limiting toxicities [ Time Frame: From initiation of inotuzumab ozogamicin through 30 days following the last dose of inotuzumab ozogamicin ]
    The number of dose-limiting toxicities will be used to determine the maximum tolerated dose combination for these combinations of drugs

  3. Informative course of treatment [ Time Frame: For each participant, up to the 29 days of study treatment ]
    Percent of patients that receive enough treatment to be informative to the study



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 enrollment
  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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03962465


Contacts
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Contact: Steve Fowler 434 243 4730 saf2qh@virginia.edu

Locations
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United States, Virginia
University of Virginia Not yet recruiting
Charlottesville, Virginia, United States, 22908
Contact: Monika Thielen    434-982-5027    mj3tc@virginia.edu   
Contact: Jennifer Law, BSN    434 297 7812    jl2ab@virginia.edu   
Principal Investigator: Michael Douvas, MD         
Sub-Investigator: Karen Ballen, MD         
Sub-Investigator: Michael Keng, MD         
Sponsors and Collaborators
University of Virginia
Pfizer
Vanderbilt University
University of Wisconsin, Madison
Virginia Commonwealth University
Investigators
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Principal Investigator: Michael Douvas, MD University of Virginia

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Responsible Party: Michael Douvas, MD, Associate Professor of Medicine and Pediatrics, University of Virginia
ClinicalTrials.gov Identifier: NCT03962465     History of Changes
Other Study ID Numbers: 21417
First Posted: May 24, 2019    Key Record Dates
Last Update Posted: May 24, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Inotuzumab Ozogamicin
Burkitt Lymphoma
Leukemia
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Lymphoma
Cytarabine
Prednisone
Methotrexate
Vincristine
Daunorubicin
Pegaspargase
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic