Patient case: 69-year-old female with melanoma; genetic feature: high serum LDH levels

Clinical trial: Study of Blinatumomab in Japanese Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia

Summary: Open-label combined two-part multi-center clinical study to evaluate the efficacy, safety, and tolerabillity of blinatumomab in adult and pediatric Japanese subjects with R/R B-precursor ALL.
  The Phase 1b part will investigate the safety, efficacy, PK and PD of blinatumomab in adult Japanse subects with R/R B-precursor ALL to determine the MTD (maximum tolerated dose) in both adult and pediatric subjects. Once a dose has been selected in the Phase 1b part, the Phase 2 part will assess the safety and efficacy of the recommeded dose level of blinatumomab identified in the Phase 1b portion of the study in the adult study population.


Eligibility: Adult Subjects Key Inclusion Criteria:
  -  Age >/= 18 years old at enrollment
  -  Subjects with Philadelphia-negative B-precursor ALL, with any of the following:
  -  Relapsed or refractory after first line therapy with first remission duration
  ≤ 12 months; or
  -  Relapsed or refractory after first salvage therapy; or
  -  Relapsed or refractory within 12 months of alloHSCT
  -  Greater than 5% blasts in bone marrow
  Pediatric Subjects Key Inclusion Criteria:
  -  Age < 18 years-old at enrollment
  -  Relapsed/refractory disease, defined as one of the following:
  -  second or later bone marrow relapse;
  -  any marrow relapse after alloHSCT; or
  -  Refractory to other treatments: o For subjects in first relapse: failure to achieve a CR following a full standard reinduction chemotherapy regimen o For subjects who have not achieved a first remission: failure to achieve remission following a full standard induction regimen
  -  Greater than 5% blasts in bone marrow
  -  Karnofsky performance status ≥ 50% for subjects ≥ 16 years
  -  Lansky performance status ≥ 50% for subjects < 16 years
  Exclusion Criteria:
  -  History of malignancy other than ALL within 5 years prior to start of protocol-specified therapy with the exception of:
  -  Malignancy treated with curative intent and with no known active disease present for 5 years before enrollment and felt to be at low risk for recurrence by the treating physician
  -  Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  -  Adequately treated cervical carcinoma in situ without evidence of disease
  -  Adequately treated breast ductal carcinoma in situ without evidence of disease
  -  Prostatic in situ without evidence of disease
  -  Adequately treated mucosal gastric cancer or mucosal colorectal cancer without evidence of disease
  -  Diagnosis of Burkitt's Leukemia according to World Health Organization (WHO) classification
  -  History or presence of clinically relevant cental nervous system (CNS) pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis; with the exception of well controlled CNS leukemia
  -  Active ALL in the CNS (confirmed by cerebrospinal fluid [CSF analysis]) or testes
  -  Isolated extramedullary disease
  -  Current autoimmune disease or history of autoimmune disease with potential CNS involvement
  -  Autologous HSCT within 6 weeks prior to start of blinatumomab treatment
  -  AlloHSCT within 12 weeks prior to start of blinatumomab treatment
  -  Any active acute Graft-versus-Host Disease (GvHD), grade 2-4 according to Glucksberg criteria or active chronic GvHD requiring systemic treatment
  -  Any systemic therapy against GvHD within 2 weeks prior to start of blinatumomab treatment
  -  Cancer chemotherapy within 2 weeks prior to start of blinatumomab treatment (Intrathecal chemotherapy and dexamethasone are allowed until start of blinatumomab treatment. Pediatric subjects only: Tyrosine kinase inhibitors and/or low dose maintenance therapy such as vinca alkaloids, mercaptopurine, methotrexate, glucocorticoids, intrathecal chemotherapy and dexamethasone are allowed until start of blinatumomab)
  -  Radiotherapy within 2 weeks prior to start of blinatumomab treatment
  -  Immunotherapy (eg, rituximab) within 6 weeks prior to start of blinatumomab treatment
  -  Subject received prior anti-CD19 therapy
  -  Eligibility for alloHSCT at the time of enrollment (as defined by disease status, performance status and availability of donor)
  -  Abnormal screening laboratory values as defined below:
  -  AST (SGOT) and/or ALT (SGPT) and/or ALP >= 5 x upper limit of normal (ULN)
  -  Total bilirubin >= 1.5 x ULN (unless related to GilbertLs or Meulengracht disease)
  -  Creatinine >= 1.5 ULN for age, or creatinine clearance < 60 mL/min
  -  Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HBsAg positive) or hepatitis C virus (anti-HCV positive)
  -  Currently receiving treatment in another investigational device or drug study, or less than 4 weeks since ending treatment on another investigational device or drug study(s). Other investigational procedures while participating in this study are excluded.
  -  Subject has known sensitivity to immunoglobulins or any of the products or components to be administered during dosing
  -  Subject likely to not be available to complete all protocol-required study visits or procedures, including follow-up visits, and/or to comply with all required study procedures to the best of the subject's and investigator's knowledge
  -  Previous treatment with blinatumomab
  -  Chemotherapy related toxicities (excluding hematologic) that have not resolved to <= grade 2
  -  Symptoms and/or clinical signs and/or radiological and/or sonographic signs that indicate an acute or uncontrolled chronic infection, any other concurrent disease or medical condition that could be exacerbated by the treatment or would seriously complicate compliance with the protocol
  -  Pregnant or breastfeeding women, or women who are planning to become pregnant or breastfeed during treatment and for an additional time period after discontinuing treatment (time period will match required female contraception timeframe outlined in Section 6.12.1)
  -  Female subjects of childbearing potential unwilling to use contraception as outlined in Section 6.12.1. Note: The pregnancy, breastfeeding and contraceptive requirements are specific for blinatumomab. The investigator is responsible for providing the subject (male and female) with pregnancy and breastfeeding (female only) avoidance requirements for other medications given during the study.

Relevance to patient case: not relevant