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Purpose

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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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

Phase
Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Induction/Consolidation Phase - All Participants 		All participants in this study 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
  • Drug: Inotuzumab ozogamicin
    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.
    Other names:
    • Besponsa
  • Drug: Dasatinib
    Dasatinib is a prescription treatment for adults with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML).
    Other names:
    • SPRYCEL
  • Drug: Dexamethasone
    Dexamethasone is a steroid that prevents the release of substances in the body that cause inflammation.
    Other names:
    • Decadron®, Dexamethasone Intensol®, Dexasone, Solurex®, and Baycadron®
  • Drug: Methotrexate
    Methotrexate is a chemotherapy drug that is used to treat certain types of cancer and leukemia.
    Other names:
    • Otrexup™, Rasuvo®, Rheumatrex® and Trexall™. MTX, Amethopterin, and Methotrexate Sodium
Experimental
Maintenance Phase - Participants in CMR (Schema 2 Regimen - Enrollment Completed) 		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 treatment using dasatinib combined with POMP chemotherapy and intrathecal methotrexate. POMP chemotherapy consists of the drugs 6-Mercaptopurine + Vincristine + Methotrexate + Prednisone.
  • Drug: Dasatinib
    Dasatinib is a prescription treatment for adults with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML).
    Other names:
    • SPRYCEL
  • Drug: Methotrexate
    Methotrexate is a chemotherapy drug that is used to treat certain types of cancer and leukemia.
    Other names:
    • Otrexup™, Rasuvo®, Rheumatrex® and Trexall™. MTX, Amethopterin, and Methotrexate Sodium
  • Drug: Vincristine
    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.
    Other names:
    • Oncovin and Vincasar Pfs
  • Drug: Ponatinib
    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.
    Other names:
    • Iclusig
  • Drug: Purinethol (6-Mercaptopurine)
    Purinethol is a chemotherapy drug that is used to treat certain types of cancer and leukemia.
  • Drug: Prednisone
    Prednisone is steroid given during chemotherapy treatments.
Experimental
Maintenance Phase - Participants Not in CMR (Schema 2 Regimen - Enrollment Completed) 		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 (CMR). Participants in this arm will receive treatment using ponatinib combined combined with POMP chemotherapy and intrathecal methotrexate. A single 28-day cycle of inotuzumab will be given after initial 84 days of maintenance treatment if CMR has not been achieved. POMP chemotherapy consists of the drugs 6-Mercaptopurine + Vincristine + Methotrexate + Prednisone.
  • Drug: Inotuzumab ozogamicin
    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.
    Other names:
    • Besponsa
  • Drug: Methotrexate
    Methotrexate is a chemotherapy drug that is used to treat certain types of cancer and leukemia.
    Other names:
    • Otrexup™, Rasuvo®, Rheumatrex® and Trexall™. MTX, Amethopterin, and Methotrexate Sodium
  • Drug: Vincristine
    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.
    Other names:
    • Oncovin and Vincasar Pfs
  • Drug: Ponatinib
    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.
    Other names:
    • Iclusig
  • Drug: Purinethol (6-Mercaptopurine)
    Purinethol is a chemotherapy drug that is used to treat certain types of cancer and leukemia.
  • Drug: Prednisone
    Prednisone is steroid given during chemotherapy treatments.
Experimental
Interim/Maintenance Phase - Participants in CMR (Schema 3 Regimen ) 		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 treatment using dasatinib and intrathecal methotrexate.
  • Drug: Dasatinib
    Dasatinib is a prescription treatment for adults with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML).
    Other names:
    • SPRYCEL
  • Drug: Methotrexate
    Methotrexate is a chemotherapy drug that is used to treat certain types of cancer and leukemia.
    Other names:
    • Otrexup™, Rasuvo®, Rheumatrex® and Trexall™. MTX, Amethopterin, and Methotrexate Sodium
Experimental
Maintenance Phase - Participants Not in CMR (Schema 3 Regimen) 		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 treatment using ponatinib combined with intrathecal methotrexate. A single 28-day cycle of inotuzumab will be given after initial 84 days of maintenance treatment if CMR has not been achieved.
  • Drug: Methotrexate
    Methotrexate is a chemotherapy drug that is used to treat certain types of cancer and leukemia.
    Other names:
    • Otrexup™, Rasuvo®, Rheumatrex® and Trexall™. MTX, Amethopterin, and Methotrexate Sodium
  • Drug: Ponatinib
    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.
    Other names:
    • Iclusig

Recruiting Locations

University of Chicago Medical Center
Chicago, Illinois 60615
Contact:
Wendy Stock, MD
773-834-8982
cancerclinicaltrials@bsd.uchicago.edu

More Details

Status
Recruiting
Sponsor
University of Chicago

Study Contact

Cancer Clinical Trials Office
1-855-702-8222
cancerclinicaltrials@bsd.uchicago.edu

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.