Inotuzumab Ozogamicin with Standard Chemotherapy Regimen for the Treatment of Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia
Inotuzumab Ozogamicin with Standard Chemotherapy Regimen for the Treatment of Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia
This phase I trial studies the side effects and best dose of inotuzumab ozogamicin when given with 3 and 4 drug standard chemotherapy regimen in treating patients with B-cell acute lymphoblastic leukemia that has come back (relapsed) or does not respond to treatment (refractory). Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a toxic agent called ozogamicin. Inotuzumab attaches to CD22 positive cancer cells in a targeted way and delivers ozogamicin to kill them. Chemotherapy drugs, such as daunorubicin, vincristine, cytarabine, methotrexate, and pegaspargase, 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. Anti-inflammatory drugs, such as prednisone lower the bodys immune response and are used with other drugs in the treatment of some types of cancer. Giving inotuzumab ozogamicin with standard chemotherapy may work better in treating patients with B-cell acute lymphoblastic leukemia compared to inotuzumab ozogamicin alone.
Leukemia,
Phase I
Phase I
Adults
Chemotherapy - cytotoxic,
Mol. targeted/Immunotherapy/Biologics
Daunorubicin (Daunomycin),
Inotuzumab Ozogamicin,
Pegaspargase (PEG-ASP),
Prednisone,
Vincristine
Oluwole, Olalekan
International
Vanderbilt University
08-09-2021
Treatment
VICCHEMP20108
NCT03962465
Eligibility
16 Years
BOTH
NO
Inclusion Criteria:
Provision of signed and dated informed consent form
Stated willingness to comply with all study procedures and availability for the duration of the study
Diagnosed with CD-22 positive B-cell acute lymphoblastic leukemia or B-cell lymphoblastic lymphoma (Philadelphia chromosome negative) * For the purposes of this study, CD-22 positive will be defined based on the analysis completed for diagnostic purposes
Male or female, aged 16-60 years
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Left ventricular ejection fraction > 50% measured by echocardiogram or multigated acquisition scan (MUGA)
Either relapsed following remission after initial induction therapy or refractory to induction therapy
Serum creatinine / creatinine clearance = 50 ml/min by Cockcroft-Gault formula
Bilirubin =
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =
Alkaline phosphatase =
For females of reproductive potential: negative pregnancy test
For females and males of reproductive potential: agreement to use adequate contraception during study participation and for an additional 1 year after the end of study treatment
Agreement to adhere to lifestyle considerations throughout study duration and for 1 year following last study treatment
Exclusion Criteria:
Past receipt of a total of >= 300 mg/m^2 doxorubicin equivalents (600 mg/m^2 daunorubicin, 60 mg/m^2 idarubicin, 75 mg/m^2 mitoxantrone)
Current or past history of pancreatitis
QT interval on electrocardiogram (ECG) > 0.45 by Framingham formula
Known congestive heart failure
Known allergy to asparaginase (only an exclusion criteria for participants enrolling in part 2)
Presence of central nervous system (CNS) disease
Pregnancy or lactation
Chronic liver disease including chronic active hepatitis and/or cirrhosis
Active hepatitis B virus (HBV) by core antibody, surface antigen (HBsAg) or viral load
Active hepatitis C virus (HCV) (positive antibody test confirmed by viral load if antibody test is positive)
Known history of infection with human immunodeficiency virus (HIV)
Active or uncontrolled infections
Abnormal baseline hepatic ultrasound (including Dopplers)
Prior allogeneic stem cell transplant
Prior use of inotuzumab ozogamicin
Known diagnosis of hemochromatosis with iron overload
Treatment with steroids or hydroxyurea for more than 7 days with each within the 2 weeks prior to registration - that is, each is allowed for up to 7 days
Gastrointestinal tract disease causing the inability to take oral medication, malabsorption syndrome, a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory gastrointestinal (GI) disease, or inability to swallow medications
Philadelphia chromosome positive B-cell acute lymphoblastic leukemia (ALL)
Provision of signed and dated informed consent form
Stated willingness to comply with all study procedures and availability for the duration of the study
Diagnosed with CD-22 positive B-cell acute lymphoblastic leukemia or B-cell lymphoblastic lymphoma (Philadelphia chromosome negative) * For the purposes of this study, CD-22 positive will be defined based on the analysis completed for diagnostic purposes
Male or female, aged 16-60 years
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Left ventricular ejection fraction > 50% measured by echocardiogram or multigated acquisition scan (MUGA)
Either relapsed following remission after initial induction therapy or refractory to induction therapy
Serum creatinine / creatinine clearance = 50 ml/min by Cockcroft-Gault formula
Bilirubin =
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =
Alkaline phosphatase =
For females of reproductive potential: negative pregnancy test
For females and males of reproductive potential: agreement to use adequate contraception during study participation and for an additional 1 year after the end of study treatment
Agreement to adhere to lifestyle considerations throughout study duration and for 1 year following last study treatment
Exclusion Criteria:
Past receipt of a total of >= 300 mg/m^2 doxorubicin equivalents (600 mg/m^2 daunorubicin, 60 mg/m^2 idarubicin, 75 mg/m^2 mitoxantrone)
Current or past history of pancreatitis
QT interval on electrocardiogram (ECG) > 0.45 by Framingham formula
Known congestive heart failure
Known allergy to asparaginase (only an exclusion criteria for participants enrolling in part 2)
Presence of central nervous system (CNS) disease
Pregnancy or lactation
Chronic liver disease including chronic active hepatitis and/or cirrhosis
Active hepatitis B virus (HBV) by core antibody, surface antigen (HBsAg) or viral load
Active hepatitis C virus (HCV) (positive antibody test confirmed by viral load if antibody test is positive)
Known history of infection with human immunodeficiency virus (HIV)
Active or uncontrolled infections
Abnormal baseline hepatic ultrasound (including Dopplers)
Prior allogeneic stem cell transplant
Prior use of inotuzumab ozogamicin
Known diagnosis of hemochromatosis with iron overload
Treatment with steroids or hydroxyurea for more than 7 days with each within the 2 weeks prior to registration - that is, each is allowed for up to 7 days
Gastrointestinal tract disease causing the inability to take oral medication, malabsorption syndrome, a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory gastrointestinal (GI) disease, or inability to swallow medications
Philadelphia chromosome positive B-cell acute lymphoblastic leukemia (ALL)
