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

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The University of Chicago

Status and phase

Enrolling
Phase 2

Conditions

Lymphoblastic Leukemia
Acute Lymphoblastic Leukemia
ph+ Acute Lymphoblastic Leukemia

Treatments

Drug: Ponatinib
Procedure: Allogenic Stem Cell Transplantation
Drug: Methotrexate
Drug: Vincristine
Drug: Methotrexate for Injection
Drug: Dasatinib
Drug: Inotuzumab ozogamicin
Drug: Dexamethasone

Study type

Interventional

Funder types

Other

Identifiers

NCT04747912
IRB20-1749

Details and patient eligibility

About

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.

Enrollment

25 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Sequential Assignment

Masking

None (Open label)

25 participants in 3 patient groups

Treatment Arm - Induction/Consolidation Phase - All Participants
Experimental group
Description:
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:
Drug: Dexamethasone
Drug: Inotuzumab ozogamicin
Drug: Dasatinib
Drug: Methotrexate for Injection
Treatment Arm - Interim/Maintenance Phase - Participants in CMR
Experimental group
Description:
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:
Drug: Dexamethasone
Drug: Inotuzumab ozogamicin
Drug: Dasatinib
Drug: Methotrexate for Injection
Drug: Vincristine
Drug: Methotrexate
Procedure: Allogenic Stem Cell Transplantation
Treatment Arm - Interim/Maintenance Phase - Participants Not in CMR
Experimental group
Description:
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:
Drug: Dexamethasone
Drug: Inotuzumab ozogamicin
Drug: Methotrexate for Injection
Drug: Vincristine
Drug: Methotrexate
Procedure: Allogenic Stem Cell Transplantation
Drug: Ponatinib

Trial contacts and locations

1

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Central trial contact

Wendy Stock, MD; Cancer Clinical Trials Office

Data sourced from clinicaltrials.gov

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