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Chemotherapy-free Induction Regimen and Inotuzumab Ozogamicin for the Treatment of Ph+ Acute Lymphoblastic Leukemia

Trial Status: Active

This phase II trial studies the effect of chemotherapy-free induction regimen and inotuzumab ozogamicin in treating patients with Ph+ acute lymphoblastic leukemia. Chemotherapy drugs, such as inotuzumab ozogamicin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy later than induction phase may work better than induction regimen with chemotherapy in treating Ph+ acute lymphoblastic leukemia.

Inclusion Criteria

  • Newly diagnosed, untreated patients with Ph+ B-cell acute lymphoblastic leukemia (ALL) and CD22 expression on >= 20% of blasts
  • Ages >= 18 years old
  • 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/mm^3 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
  • Creatinine clearance >= 60 mL/min, determined by the Cockcroft-Gault formula, or measured by a 24-hour urine collection
  • Aspartate aminotransferase (AST) and alanine amino transferase (ALT) =< 2.5 x upper limit of normal (ULN) (unless considered due to Gilbert’s syndrome or of non-hepatic origin i.e., leukemic involvement)
  • Bilirubin =< 1.5 x ULN (unless considered due to Gilbert’s syndrome or of non-hepatic origin i.e., leukemic involvement)
  • 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 (IEC)/Institutional Review Board (IRB), prior to the initiation of 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 InO 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 (i.e., meet at least one of the following criteria): * 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

Exclusion Criteria

  • 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 (e.g., 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
  • Corrected T interval by Fridericia's formula (QTcF) > 500 msec (based on the average of 3 consecutive electrocardiography [ECG]s)
  • History of chronic liver disease (e.g., 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
  • 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
  • Participation in other investigational studies during active treatment phase
  • 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

Illinois

Chicago
University of Chicago Comprehensive Cancer Center
Status: ACTIVE
Contact: Wendy Stock
Phone: 773-834-8982

PRIMARY OBJECTIVE:

I. To evaluate the rates of complete clinical remission with at least a major molecular remission at 60 days in patients with inotuzumab ozogamicin (InO) added to a tyrosine kinase inhibitor (TKI)-steroid based induction regimen.

SECONDARY OBJECTIVES:

I. To evaluate long-term efficacy, safety, and survival outcomes in patients with InO added to a TKI-steroid based induction regimen.

II. To evaluate the complete molecular response (CMR) rate in patients treated with InO and ponatinib in addition to evaluating the safety of this combination.

OUTLINE:

COURSE 1 (INDUCATION PHASE, 28 DAYS): Patients receive dasatinib orally (PO) daily on days 1-28, dexamethasone PO or intravenously (IV) on days 1-7 and 15-21, inotuzumab ozogamicin IV on days 8, 15, and 22, and methotrexate intrathecally (IT) on days 1 and 28. Treatment continues in the absence of disease progression or unacceptable toxicity.

COURSE 2 (CONSOLIDATION PHASE, 28 DAYS): Patients receive dasatinib PO daily on days 1-28, inotuzumab ozogamicin IV on days 1, 8, and 15, and methotrexate IT on days 1 and 28. Treatment continues in the absence of disease progression or unacceptable toxicity.

COURSE 3 (INTERIM MAINTENANCE PHASE, 84 DAYS): Patients with morphologic complete response (CR) and CMR receive vincristine IV on days 1, 29, and 57, dexamethasone PO or IV on days 1-5, 29-33, 57-61, and PO on days 1-84, methotrexate PO on days 22, 29, 36, 43, 50, 57, 64, 71, and 78, dasatinib PO on days 1-84, and methotrexate IT on days 1, 15, and 28. Patients with morphologic CT but no CMR receive vincristine IV on days 1, 29, and 57, dexamethasone PO or IV on days 1-5, 29-33, 57-61, and PO on days 1-84, methotrexate PO on days 22, 29, 36, 43, 50, 57, 64, 71, and 78, ponatinib PO on days 1-84, and methotrexate IT on days 1, 15, and 28. Treatment continues in the absence of disease progression or unacceptable toxicity.

COURSE 4 (MAINTENANCE PHASE, 28 DAYS): Patients without dasatinib treatment during Course 3 receive dasatinib PO daily on days 1-28, inotuzumab ozogamicin IV on days 1, 8, and 15, and methotrexate IT on days 1 and 28. Patients without ponatinib treatment during Course 3 receive ponatinib PO daily on days 1-28, inotuzumab ozogamicin IV on days 1, 8, and 15, and methotrexate IT on days 1 and 28. Treatment continues in the absence of disease progression or unacceptable toxicity.

COURSE 5+ (MAINTENANCE PHASE, 84 DAYS): Patients with treatment of dasatinib or ponatinib and not in CMR after Course 4 are off study. Patients without treatment of dasatinib and in CMR after Course 4 receive vincristine IV on days 1, 29, and 57, dexamethasone PO or IV on days 1-5, 29-33, 57-61, and PO on days 1-84, methotrexate PO on days 22, 29, 36, 43, 50, 57, 64, 71, and 78, dasatinib PO daily on days 1-84, and methotrexate IT on days 1 and 29. Patients without treatment of pronatinib and in CMR after Course 4 receive vincristine IV on days 1, 29, and 57, dexamethasone PO or IV on days 1-5, 29-33, 57-61, and PO on days 1-84, methotrexate PO on days 22, 29, 36, 43, 50, 57, 64, 71, and 78, ponatinib PO daily on days 1-84, and methotrexate IT on days 1 and 29. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 12 weeks.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
University of Chicago Comprehensive Cancer Center

Principal Investigator
Wendy Stock

  • Primary ID IRB20-1749
  • Secondary IDs NCI-2021-02767
  • Clinicaltrials.gov ID NCT04747912