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

NCT03962465 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 21417
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 4

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 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.

Conditions

B-cell Acute Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (3)

• 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.

• 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

• 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

Study Arms (2)

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)

Drug: Inotuzumab ozogamicin; Drug: Prednisone Pill; Drug: Daunorubicin; Drug: Vincristine; Drug: Cytarabine; Drug: 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)

Drug: Inotuzumab ozogamicin; Drug: Prednisone Pill; Drug: Daunorubicin; Drug: Vincristine; Drug: Cytarabine; Drug: Methotrexate; Drug: Pegaspargase

Interventions

Inotuzumab ozogamicin DRUG

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

Also known as: Besponsa

3-drug re-induction regimen with inotuzumab; 4-drug re-induction regimen with inotuzumab

Prednisone Pill DRUG

Taken daily days 1-28 by mouth

Also known as: Deltasone

3-drug re-induction regimen with inotuzumab; 4-drug re-induction regimen with inotuzumab

Daunorubicin DRUG

By IV, given on days 1, 8, 15, and 22

Also known as: Cerubidine, daunomycin, rubidomycin

3-drug re-induction regimen with inotuzumab; 4-drug re-induction regimen with inotuzumab

Vincristine DRUG

By IV, given on days 1, 8, 15, and 22

Also known as: Oncovin, Vincasar, Leurocristine

3-drug re-induction regimen with inotuzumab; 4-drug re-induction regimen with inotuzumab

Cytarabine DRUG

Intrathecal, administered on day 1 only

Also known as: Ara-C, Cytosar-U

3-drug re-induction regimen with inotuzumab; 4-drug re-induction regimen with inotuzumab

Methotrexate DRUG

Intrathecal, administered on days 8 and 29

Also known as: Otrexup, Rasuvo, Rheumatrex, Trexall, MTX, Amethopterin

3-drug re-induction regimen with inotuzumab; 4-drug re-induction regimen with inotuzumab

Pegaspargase DRUG

By IV, given on day 4

Also known as: Oncospar

4-drug re-induction regimen with inotuzumab

Eligibility Criteria

• Age: 16 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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 will be defined based on the analysis completed for diagnostic purposes.
• Male or female, aged 16-60 years
• ECOG performance status of 0-2
• Left ventricular ejection fraction ≥ 50% 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 (elevation exceeding this threshold of either AST OR ALT would not meet eligibility)
• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of Virginia: lead
• Pfizer: collaborator
• Vanderbilt University: collaborator
• University of Wisconsin, Madison: collaborator
• Virginia Commonwealth University: collaborator

Study Sites (4)

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

VCU Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Burkitt Lymphoma

Interventions

Inotuzumab Ozogamicin; Prednisone; Daunorubicin; Vincristine; Cytarabine; Methotrexate; pegaspargase

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Aminopterin; Pterins; Pteridines

Study Officials

• Michael Douvas, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine and Pediatrics

Model Details: 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.

Study Record Dates

• First Submitted: May 22, 2019
• First Posted: May 24, 2019
• Study Start: July 22, 2022
• Primary Completion: July 15, 2023
• Study Completion (Estimated): July 1, 2026
• Last Updated: August 22, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)