Study Stopped
Enrollment goal met; pending amendment to expand study
Study of Chemotherapy-Free Induction Regimen for Ph+ Acute Lymphoblastic Leukemia With Inotuzumab Ozogamicin (InO)
A Phase II Study of a Chemotherapy-Free Induction Regimen for Ph+ Acute Lymphoblastic Leukemia (ALL) Incorporating Inotuzumab Ozogamicin (InO)
1 other identifier
interventional
25
1 country
1
Brief Summary
This research study will add an anti-cancer drug (called inotuzumab ozogamicin also known as "InO") to treatment for participants with newly diagnosed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). Doctors leading this study hope to learn if adding InO to standard induction treatment for Ph+ ALL will lead to quicker, complete molecular remission (where the disease is not detectable even with very sensitive testing techniques). The purpose of this research is to gather information regarding the effectiveness of InO in newly-diagnosed Ph+ ALL patients that have not yet received treatment.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Mar 2021
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 5, 2021
CompletedFirst Posted
Study publicly available on registry
February 10, 2021
CompletedStudy Start
First participant enrolled
March 2, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 1, 2027
March 30, 2026
March 1, 2026
6 years
February 5, 2021
March 24, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of Participants Who Enter Complete Clinical Remission at 60 Days as Defined by Criteria Set By The International Scale
Complete clinical remission (when there are no signs of the disease) with a major molecular remission at 60 days as defined by participants who have a low ratio (less than or equal to .01%) of BCR-ABL1gene in their blood, according to criteria set by the International Scale for p210 BCR-ABL1.
60 days
Secondary Outcomes (7)
Overall Survival
36 months
Duration of Response
36 months
Duration of Complete Response
36 months
Progression Free Survival
36 months
Disease Control Rate Based on Number of Participants Who Respond to Treatment After 3 Months
36 months
- +2 more secondary outcomes
Study Arms (3)
Treatment Arm - Induction/Consolidation Phase - All Participants
EXPERIMENTALAll participants in this arm will receive the same first round of treatment as part of induction/consolidation therapy. This treatment will use inotuzumab ozogamicin combined with anti-cancer drugs. The additional treatment that participants receive after this first round of treatment will vary based on the participant's response to induction therapy. This phase of treatment will last for 60 days. All participants in this arm will receive the following treatment: Treatment Course I (Induction Phase, 28 days): * Dasatinib 140mg daily continuous * Dexamethasone 10mg/m\^2 PO or IV Days 1-7 and Day 15-Day 22 * InO 0.8mg/m2 Day 8; 0.5mg/m2 D15, 0.5mg/m2 Day 22 * Intrathecal methotrexate 15mg Day 1, Day 28 Treatment Course II (Consolidation Phase, 28 days): * Dasatinib 140mg daily continuous * InO: If in CR/CRi 0.5mg/m2 Day 1, Day 8, Day 15; If not in CR/CRi 0.8mg/m2 on Day 1, 0.5mg/m2 Day 8 and Day 15 * Intrathecal methotrexate 15mg Day 1, Day 28
Treatment Arm - Interim/Maintenance Phase - Participants in CMR
EXPERIMENTALThis study arm is for participants who no longer show any detectable signs of BCR-ABL1 (a cancer-causing gene) in response to the previous phase of induction/consolidation treatment (also known as being in "complete molecular remission" or CMR). Participants in this arm will receive 3 courses of interim/maintenance treatment using dasatinib combined with other anti-cancer drugs. Inotuzumab ozogamicin will be added during the fourth course of treatment. These treatments will be given in 28-day and 84-day cycles. If the participant achieves complete molecular remission (no signs of BCR-ABL gene) after 60 days (or more) of treatment, then the treating physician may take the participant off the study for allogenic stem cell transplantation surgery. If the participant does not undergo allogeneic stem cell transplantation after achieving complete molecular remission, they will complete 3 additional courses of maintenance treatment.
Treatment Arm - Interim/Maintenance Phase - Participants Not in CMR
EXPERIMENTALThis study arm is for participants whose cancer responded to induction/consolidation treatment, but still shows detectable signs of BCR-ABL1 (a cancer-causing gene), so they are not in complete molecular remission. Participants in this arm will receive 3 courses of treatment using ponatinib combined with other anti-cancer drugs. Inotuzumab ozogamicin will be added during the 4th treatment course. These treatments will be given in 28-day and 84-day cycles. If the participant achieves complete molecular remission (no signs of BCR-ABL gene) after 60 days (or more) of treatment, the treating physician may take the participant off the study for allogenic stem cell transplantation surgery. If the participant does not undergo allogeneic stem cell transplantation after achieving complete molecular remission (CMR), they will complete 3 additional courses of maintenance treatment. If the participant doesn't achieve CMR after 4th treatment course, they will be removed from the study.
Interventions
Inotuzumab ozogamicin, sold under the brand name Besponsa, is an anti-cancer drug used to treat relapsed or refractory B-cell precursor acute lymphoblastic leukemia.
Dasatinib is a prescription treatment for adults with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML).
Dexamethasone is a steroid that prevents the release of substances in the body that cause inflammation.
Methotrexate is a chemotherapy drug that is used to treat certain types of cancer and leukemia.
Vincristine, also known as leurocristine and marketed under the brand name Oncovin among others, is a chemotherapy medication used to treat various types of cancer such as acute lymphocytic leukemia, acute myeloid leukemia, Hodgkin's disease, neuroblastoma, and small cell lung cancer among others.
A drug used to treat chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia. It is used in patients whose cancer has the T315I mutation or whose cancer cannot be treated with other tyrosine kinase inhibitors. It is also being studied in the treatment of other types of cancer. Ponatinib blocks BCR-ABL, which may help keep cancer cells from growing and may kill them.
Methotrexate is a chemotherapy drug that is used to treat certain types of cancer and leukemia. When given intrathecally, it prevents leukemia cells entering the cerebrospinal fluid (CSF) around the spine and brain. Intrathecal chemotherapy is administered during a procedure called a lumbar puncture or through an ommaya reservoir (shunt).
A procedure in which a patient receives healthy blood-forming cells (stem cells) from a donor to replace their own stem cells that have been destroyed by treatment with radiation or high doses of chemotherapy. In an allogeneic stem cell transplant, the healthy stem cells may come from the blood or bone marrow of a related donor who is not an identical twin of the patient or from an unrelated donor who is genetically similar to the patient. An allogeneic stem cell transplant is most often used to treat blood cancers, such as leukemia and lymphoma, and certain types of blood or immune system disorders.
Eligibility Criteria
You may qualify if:
- Must be a newly diagnosed and untreated patient with Ph+ B-cell Acute Lymphoblastic Leukemia and CD22 expression on ≥20% of blasts.
- years old or older.
- Bone marrow involvement with ≥20% lymphoblasts and demonstration of BCR-ABL1 via fluorescence in situ hybridization (FISH) studies or PCR-based testing. Patients with \>1000/mm3 lymphoblasts in the peripheral blood that cannot undergo bone marrow biopsy and aspiration due to clinical condition are also eligible.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
- Adequate organ function as confirmed by clinical/medical record.
- Patients must be at least 2 weeks from major surgery, radiation therapy, or participation in other investigational trials, and must have recovered from clinically significant toxicities related to these prior treatments.
- Patients must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee/Institutional Review Board prior to starting any screening or study-specific procedures.
- Females of childbearing potential will use effective contraception during treatment with InO and for at least 8 months after the last dose. Males with female partners of reproductive potential will use effective contraception during treatment with Inotuzumab Ozogamicin and for at least 5 months after the last dose. A patient is of childbearing potential if, in the opinion of the treating investigator, he/she is biologically capable of having children and is sexually active. Female patients who are not of childbearing potential (ie, meet at least one of the following criteria):
- a. Have undergone hysterectomy or bilateral oophorectomy; or have medically confirmed ovarian failure; or are medically confirmed to be post-menopausal (cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause).
- Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
You may not qualify if:
- Isolated extramedullary disease.
- Burkitt's or mixed-lineage leukemia.
- Active central nervous system (CNS) leukemia.
- Any prior therapy for ALL except for limited treatment (≤ 7 days) with corticosteroids or hydroxyurea and a single dose of intrathecal therapy. Patients who are being treated with chronic steroids for other reasons (eg, asthma, autoimmune disorders) are eligible.
- Current or chronic hepatitis B or C infection as evidenced by hepatitis B surface antigen and anti-hepatitis C antibody positivity, respectively, or known seropositivity for human immunodeficiency virus (HIV). HIV testing may need to be performed in accordance with local regulations or local practice. Patients with HIV but an undetectable viral load are eligible for enrollment
- Major surgery within ≤ 2 weeks before randomization.
- Unstable or severe uncontrolled medical condition (eg, unstable cardiac function or unstable pulmonary condition.
- Concurrent active malignancy other than non-melanoma skin cancer, carcinoma in situ of the cervix, or localized prostate cancer that has been definitely treated with radiation or surgery. Patients with previous malignancies are eligible provided that they have been disease free for ≥2 years or are not currently requiring treatment.
- Uncontrolled cardiac disease.
- QTcF \> 500 msec (based on the average of 3 consecutive ECGs).
- History of chronic liver disease (eg, cirrhosis) or suspected alcohol abuse.
- History of hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS).
- Evidence of uncontrolled current serious active infection including sepsis, bacteremia, fungemia, or patients with a recent history (within 4 months) of deep tissue infections such as fasciitis or osteomyelitis.
- Medications known to predispose to Torsades de Pointes are prohibited throughout the treatment period of the study.
- Pregnant females; breastfeeding females; males with female partners of reproductive potential and females of childbearing potential not using highly effective contraception or not agreeing to continue highly effective contraception for a minimum of 5 months after the last dose of investigational product if male and 8 months after the last dose of investigational product if female.
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University of Chicago Medical Center
Chicago, Illinois, 60615, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Wendy Stock, MD
University of Chicago
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 5, 2021
First Posted
February 10, 2021
Study Start
March 2, 2021
Primary Completion (Estimated)
March 1, 2027
Study Completion (Estimated)
March 1, 2027
Last Updated
March 30, 2026
Record last verified: 2026-03