Study of Chemotherapy-Free Induction Regimen for Ph+ Acute Lymphoblastic Leukemia With Inotuzumab Ozogamicin (InO)

Phase 2

Recruiting

• Conditions: Lymphoblastic Leukemia; Acute Lymphoblastic Leukemia; ph+ Acute Lymphoblastic Leukemia
• Interventions: Drug: Inotuzumab ozogamicin; Drug: Dasatinib; Drug: Dexamethasone; Drug: Methotrexate for Injection; Drug: Methotrexate; Drug: Vincristine; Drug: Ponatinib; Procedure: Allogenic Stem Cell Transplantation

• Registration Number: NCT04747912
• Lead Sponsor: University of Chicago

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-02-05
• Study First Submitted QC: 2021-02-05
• Study First Posted: 2021-02-10
• Study Start: 2021-03-02
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-04
• Last Update Posted: 2025-03-07
• Primary Completion: 2027-03-01
• Study Completion: 2027-03-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

1. Must be a newly diagnosed and untreated patient with Ph+ B-cell Acute Lymphoblastic Leukemia and CD22 expression on ≥20% of blasts.

2. 18 years old or older.

3. 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.

4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

5. Adequate organ function as confirmed by clinical/medical record.

6. 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.

7. 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.

8. 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).

9. Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria

1. Isolated extramedullary disease.
2. Burkitt's or mixed-lineage leukemia.
3. Active central nervous system (CNS) leukemia.
4. 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.
5. 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
6. Major surgery within ≤ 2 weeks before randomization.
7. Unstable or severe uncontrolled medical condition (eg, unstable cardiac function or unstable pulmonary condition.
8. 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.
9. Uncontrolled cardiac disease.
10. QTcF > 500 msec (based on the average of 3 consecutive ECGs).
11. History of chronic liver disease (eg, cirrhosis) or suspected alcohol abuse.
12. History of hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS).
13. 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.
14. Medications known to predispose to Torsades de Pointes are prohibited throughout the treatment period of the study.
15. 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.
16. Patients who are investigational site staff members or relatives of those site staff members or patients who are Pfizer employees directly involved in the conduct of the trial.
17. Participation in other investigational studies during active treatment phase.
18. Other severe acute, chronic medical, psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the Study Lead Principal Investigator, would make the patient inappropriate for entry into this study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Treatment Arm - Interim/Maintenance Phase - Participants in CMR	Allogenic Stem Cell Transplantation	This 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	Inotuzumab ozogamicin	This 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.
Treatment Arm - Interim/Maintenance Phase - Participants Not in CMR	Allogenic Stem Cell Transplantation	This 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.
Treatment Arm - Induction/Consolidation Phase - All Participants	Methotrexate for Injection	All 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	Methotrexate for Injection	This 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	Methotrexate for Injection	This 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.
Treatment Arm - Induction/Consolidation Phase - All Participants	Inotuzumab ozogamicin	All 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 - Induction/Consolidation Phase - All Participants	Dasatinib	All 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 - Induction/Consolidation Phase - All Participants	Dexamethasone	All 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	Inotuzumab ozogamicin	This 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 in CMR	Dexamethasone	This 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 in CMR	Vincristine	This 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 in CMR	Dasatinib	This 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 in CMR	Methotrexate	This 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	Dexamethasone	This 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.
Treatment Arm - Interim/Maintenance Phase - Participants Not in CMR	Methotrexate	This 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.
Treatment Arm - Interim/Maintenance Phase - Participants Not in CMR	Vincristine	This 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.
Treatment Arm - Interim/Maintenance Phase - Participants Not in CMR	Ponatinib	This 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.

Primary Outcome Measures

Name	Time	Method
Number of Participants Who Enter Complete Clinical Remission at 60 Days as Defined by Criteria Set By The International Scale	60 days	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.

Secondary Outcome Measures

Name	Time	Method
Duration of Complete Response	36 months	The length of time from the first documented complete response (when participant shows no signs of cancer) to disease progression or death as assessed by the treating investigator.
Overall Survival	36 months	The length of time from when the participant first receives study treatment to their death (due to any cause) as assessed by the treating investigator. Participants will be followed for 12 weeks after the last dose of study drug, until any study treatment-related toxicities have stabilized, or until death.
Duration of Response	36 months	The length of time from the first documented complete response (participant shows no signs of cancer) or partial response (participant shows fewer signs of cancer) to disease progression or death. Partial/complete response will be assessed by bone marrow biopsies and blood tests.
Progression Free Survival	36 months	The time from treatment administration to documented disease progression or death from any cause as assessed by the treating investigator.
Number of Participants With Documented Veno-Occlusive Disease After Treatment	36 months	The number of patients with documented veno-occlusive disease as assessed by treating investigator.
Disease Control Rate Based on Number of Participants Who Respond to Treatment After 3 Months	36 months	The disease control rate based on the number of participants who show a complete response, partial response or no changes in disease (stable disease) after 3 months as assessed by bone marrow biopsies and neutrophil/complete blood count tests.
Number of Participants with Complete Molecular Remission at 180 Days	36 months	Number of participants with complete molecular remission at 180 days as defined by the absence of a detectable BCR-ABL1 gene, according to criteria set by the International Scale for p210 BCR-ABL1. Complete molecular remission at 180 days will be assessed among participants who do not undergo allogenic stem cell transplantation after treatment.

Trial Locations

Locations (1)

University of Chicago Medical Center; 🇺🇸 Chicago, Illinois, United States