B-cell Acute Lymphoblastic LeukemiaPhase 1ALL-001NCT03962465
Phase I Study of Inotuzumab With Augmented BFM Re-Induction for Patients With Relapsed/Refractory B-cell ALL
A Phase 1 study testing Inotuzumab ozogamicin, Prednisone Pill and Daunorubicin in people with B-cell Acute Lymphoblastic Leukemia, run by University of Virginia at 4 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 16 to 60 years
- Conditions the study is for
- B-cell Acute Lymphoblastic Leukemia
- What is being tested?
- Inotuzumab ozogamicin, Prednisone Pill and Daunorubicin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 4 sitesUnited States
- Study dates
- 22 Jul 2022to Jul 2026
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Show all 11Show fewer
- 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.
Who cannot join
- 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
Show all 19Show fewer
- 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
- Treatment with steroids or hydroxyurea for more than 7 days with each within the 2 weeks prior to registration -that is, each is allowed for up to 7 days
- 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
Trial locations and contacts
4 sites in 1 country.
United States4 sites
University of Virginia
Charlottesville, Virginia, 22908
University of Wisconsin
Madison, Wisconsin, 53792
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232
VCU Massey Cancer Center
Richmond, Virginia, 23298
About this study
Official title: Phase I Study of Inotuzumab Ozogamicin With 3 and 4 Drug Augmented Berlin-Frankfurt-Münster (BFM) Re-Induction for Patients With Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia (B-ALL)
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.
Read the 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 patients 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 patients with relapsed or refractory B-ALL.
- Conditions
- B-cell Acute Lymphoblastic Leukemia
- Being tested
- Inotuzumab ozogamicin, Prednisone Pill, Daunorubicin, Vincristine, Cytarabine
- Medical subject headings
- Burkitt Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Inotuzumab ozogamicinDrug
Also called Besponsa
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
Prednisone PillDrug
Also called Deltasone
Taken daily days 1-28 by mouth
DaunorubicinDrug
Also called Cerubidine, daunomycin, rubidomycin
By IV, given on days 1, 8, 15, and 22
VincristineDrug
Also called Oncovin, Vincasar, Leurocristine
By IV, given on days 1, 8, 15, and 22
CytarabineDrug
Also called Ara-C, Cytosar-U
Intrathecal, administered on day 1 only
MethotrexateDrug
Also called Otrexup, Rasuvo, Rheumatrex, Trexall
Intrathecal, administered on days 8 and 29
PegaspargaseDrug
Also called Oncospar
By IV, given on day 4
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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) Receives: Drug: Inotuzumab ozogamicin; Drug: Prednisone Pill; Drug: Daunorubicin; Drug: Vincristine; Drug: Cytarabine; Drug: Methotrexate; Drug: Pegaspargase |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 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
Measured: For each participant, up to the 29 days of study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2019
- Study start22 Jul 2022
- Primary completion15 Jul 2023
- Study completionJul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for B-cell Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- More trials run by University of VirginiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- 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)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer, Vanderbilt University, University of Wisconsin, Madison, Virginia Commonwealth University
- Responsible party
- Principal investigator, Michael Douvas, MD, University of Virginia
- Investigators
- Michael Douvas, MD, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03962465
- Sponsor's protocol ID
- 21417
- Acronym
- ALL-001
- Status last verified
- Aug 2023
- First submitted
- 22 May 2019
- Last updated
- 22 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Inotuzumab Ozogamicin With 3 and 4 Drug Augmented Berlin-Frankfurt-Münster (BFM) Re-Induction for Patients With Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia (B-ALL)
- ClinicalTrials.gov ID
- NCT03962465
- Acronym / sponsor ID
- ALL-001 / 21417
- Conditions
- B-cell Acute Lymphoblastic Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Collaborators
- Pfizer, Vanderbilt University, University of Wisconsin, Madison, Virginia Commonwealth University
- Study start
- 22 Jul 2022 (actual)
- Primary completion
- 15 Jul 2023 (actual)
- Study completion
- Jul 2026 (estimated)
- First posted
- 24 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 patients 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 patients with relapsed or refractory B-ALL.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| 3-drug re-induction regimen with inotuzumab | Experimental | Drug: Inotuzumab ozogamicin, Drug: Prednisone Pill, Drug: Daunorubicin, Drug: Vincristine, Drug: Cytarabine, Drug: MethotrexateOne 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) |
| 4-drug re-induction regimen with inotuzumab | Experimental | Drug: Inotuzumab ozogamicin, Drug: Prednisone Pill, Drug: Daunorubicin, Drug: Vincristine, Drug: Cytarabine, Drug: Methotrexate, Drug: PegaspargaseOne 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) |
Who may qualify
- Ages
- 16 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (19 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Inotuzumab ozogamicinAlso: BesponsaBy 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 | Drug | 3-drug re-induction regimen with inotuzumab, 4-drug re-induction regimen with inotuzumab |
| Prednisone PillAlso: DeltasoneTaken daily days 1-28 by mouth | Drug | 3-drug re-induction regimen with inotuzumab, 4-drug re-induction regimen with inotuzumab |
| DaunorubicinAlso: Cerubidine, daunomycin, rubidomycinBy IV, given on days 1, 8, 15, and 22 | Drug | 3-drug re-induction regimen with inotuzumab, 4-drug re-induction regimen with inotuzumab |
| VincristineAlso: Oncovin, Vincasar, LeurocristineBy IV, given on days 1, 8, 15, and 22 | Drug | 3-drug re-induction regimen with inotuzumab, 4-drug re-induction regimen with inotuzumab |
| CytarabineAlso: Ara-C, Cytosar-UIntrathecal, administered on day 1 only | Drug | 3-drug re-induction regimen with inotuzumab, 4-drug re-induction regimen with inotuzumab |
| MethotrexateAlso: Otrexup, Rasuvo, Rheumatrex, TrexallIntrathecal, administered on days 8 and 29 | Drug | 3-drug re-induction regimen with inotuzumab, 4-drug re-induction regimen with inotuzumab |
| PegaspargaseAlso: OncosparBy IV, given on day 4 | Drug | 4-drug re-induction regimen with inotuzumab |
Primary outcome
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.
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
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2023.
- Individual participant dataSharing planned: No
Related trials for B-cell Acute Lymphoblastic Leukemia
Recruiting
A Multicenter Study to Evaluate Next-Generation Sequencing (NGS) Testing and Monitoring of B-Cell Recovery to Guide Management Following Chimeric Antigen Receptor T-cell (CART) Induced Remission in Children and Young Adults With B Lineage Acute Lymph...
B-All, Acute Lymphoblastic Leukemia
RecruitingPhase 3
A Study of Fludarabine Dosing in Children and Young Adults With B-cell Acute Lymphoblastic Leukemia
B-cell Acute Lymphoblastic Leukemia
Not yet recruiting
Busulfan-Based Versus TBI-Based Conditioning for Adult ALL-CR2 Allo-HSCT
Acute Lymphoblastic Leukemia, Hematopoietic Stem Cell Transplantation
Not yet recruitingPhase 1
BLinatumomab and iNKT in Relapsed B-Cell ALL
B-Cell ALL, ALL (Acute B-Lymphoblastic Leukemia)
RecruitingPhase 1
Anti-CRLF2-R/TSLPR Chimeric Antigen Receptor T Cells (TSLPR-CART) in Participants With Recurrent or Refractory CRLF2-R/TSLPR-Overexpressing B-Cell Acute Lymphoblastic Leukemia (B-ALL)
B-All, Acute Lymphoblastic Leukemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Douvas, MD principal investigator
University of Virginia
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Inotuzumab ozogamicin, Prednisone Pill and Daunorubicin in people with B-cell Acute Lymphoblastic Leukemia, run by University of Virginia at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Characterization of Adverse Events (CTCAE version 5) (time frame: All adverse events occurring through 30 days following last dose of inotuzumab ozogamicin.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2023.