AALL1621 A Phase 2 Study of Inotuzumab Ozogamicin (NSC# 772518, IND#133494) in Children and Young Adults with Relapsed or Refractory CD22+ B-Acute Lymphoblastic Leukemia (B-ALL)
Johns Hopkins Kimmel Cancer Center in Baltimore
In this study, we would like to test an experimental drug called inotuzumab ozogamicin (InO). InO is an antibody which is linked to a chemotherapy drug. Antibodies are large proteins which function to identify and remove foreign substances. Cancer cells have molecules on the surface of the cell called CD22. InO searches for cancer cells with CD22 and once found, InO will attach itself to the cancer cell. Once attached, the chemotherapy is brought into the cell causing the cancer cell to die. InO is considered experimental because it is not approved by the Food and Drug Administration (FDA) and is only used in research studies like this one. InO has been shown to be well-tolerated and effective against leukemia in adults. InO has only been given to a small number of children and there is limited information about the side effects children may experience. This study will help doctors understand what kind of side effects InO has in children and how well InO works to get rid of the cancer. Study doctors hope that using InO will improve the success of treatment in children and young adults with relapsed or refractory B-ALL.The overall goal of this study is to find out what effect, good and/or bad, the drug inotuzumab ozogamicin has on children and young adults with relapsed or refractory B-ALL.
Ages Eligible for Study: 1 Year to 21 Years (Child, Adult) *******Inclusion Criteria:*******•Patients must have B-ALL with greater than equal to 5% (M2 or M3) bone marrow blasts with or without extramedullary disease•Leukemic blasts must demonstrate surface expression of CD22 at the time of relapse by local/institutional flow cytometry of a bone marrow aspirate sample; (assessment of CD22 using a phycoerythrin [PE] fluorophore is strongly recommended)---In the case of an inadequate aspirate sample (dry tap), flow cytometry of peripheral blood specimen may be substituted if the patient has at least 1000/uL circulating blasts; alternatively, CD22 expression may be documented by immunohistochemistry of a bone marrow biopsy specimen•Patient must have one of the following:-Second or greater relapse;-Primary refractory disease with at least 2 prior induction attempts;-First or greater relapse refractory to at least one prior re-induction attempt•Relapsed patients previously diagnosed with B-lymphoblastic lymphoma are eligible if they have an M2 or M3 marrow at the time of enrollment on this study•Patients with Philadelphia chromosome (Ph)+ ALL must have had two prior therapy attempts including two different tyrosine kinase inhibitors (TKIs)•Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy, defined as resolution of all such toxicities to equal to less than grade 2 or lower per the inclusion/exclusion criteria prior to entering this study---Myelosuppressive chemotherapy:-Patients who relapse while receiving standard maintenance therapy will not be required to have a waiting period prior to enrollment onto this study; otherwise, at least 14 days must have elapsed since the completion of cytotoxic therapy, with the exceptions of hydroxyurea or corticosteroids used for cytoreduction-Intrathecal cytotoxic therapy: No waiting period is required for patients having received intrathecal cytarabine, methotrexate, and/or hydrocortisone; intrathecal chemotherapy given at the time of diagnostic lumbar puncture (LP) to evaluate for relapse prior to study enrollment is allowed-At least 7 days must have elapsed since the completion of therapy with a growth factor; at least 14 days must have elapsed after receiving pegfilgrastim-At least 7 days must have elapsed since completion of therapy with a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period prior to enrollment must be extended beyond the time during which adverse events are known to occur-At least 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody with the exception of blinatumomab; patients must have been off blinatumomab infusion for at least 7 days and all drug related toxicity must have resolved to grade 2 or lower as outlined in the inclusion/exclusion criteria- greater than equal to 2 weeks must have elapsed since local palliative radiation therapy (XRT) (small port); greater than equal to 3 months must have elapsed if prior cranial or craniospinal XRT was received, if greater than equal to 50% of the pelvis was irradiated, or if total-body irradiation (TBI) was received; greater than equal to 6 weeks must have elapsed if other substantial bone marrow irradiation was given-At least 90 days must have elapsed since stem cell transplant; patient must have had no more than one previous HSCT and currently have no evidence of active graft versus (vs.) host disease (GVHD)-At least 42 days must have elapsed since chimeric antigen receptor (CAR)-T cell therapy•Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2; use Karnofsky for patients greater than 16 years of age and Lansky for patients equal to less than 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score•Creatinine clearance or radioisotope glomerular filtration rate (GFR) greater than equal to 70 mL/min/1.73 m^2 or•A serum creatinine based on age/gender as follows:*1 to less than 2 years: maximum serum creatinine 0.6 mg/dL (both male and female)*2 to less than 6 years: maximum serum creatinine 0.8 mg/dL (both male and female)*6 to less than 10 years: maximum serum creatinine 1 mg/dL (both male and female)*10 to less than 13 years: maximum serum creatinine 1.2 mg/dL (both male and female)*13 to less than 16 years: maximum serum creatinine 1.5 mg/dL (male), 1.4 mg/dL (female)* greater than equal to 16 years: maximum serum creatinine 1.7 mg/dL (male), 1.4 mg/dL (female)•Direct bilirubin equal to less than 1.5 x upper limit of normal (ULN) for age, and•Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) equal to less than 3 x ULN for age
Experimental: Treatment (inotuzumab ozogamicin) Patients receive inotuzumab ozogamicin IV over 60 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
03/05/2019 05:03 AM