Inotuzumab ozogamicin for Acute Lymphoblastic Leukemia
- Conditions
- pediatric CD22-positive relapsed/refractory Acute Lymphoblastic LeukemiaMedDRA version: 21.0Level: LLTClassification code: 10063625Term: Acute lymphoblastic leukemia recurrent Class: 10029104Therapeutic area: Diseases [C] - Hemic and Lymphatic Diseases [C15]
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 169
Age (for all patients) • Patients must be = 1 and < 18 years of age at the time of enrollment. Additional criteria for limited to Stratum 1A and 1B only: • The first 3 BCP-ALL patients on dose level 1 must be aged 6 years to less than 18 years. • Then at least 2 additional patients must be enrolled from age 1 year to less than 6 years at the same dose level. • After this requirement is met, subsequent dose levels may enroll patients aged 1 year to less than 18 years. • In case 2 younger patients are not yet recruited, patients aged 6 years up to less than 18 years may continue to be enrolled at dose level 1 until a maximum of 6 patients are enrolled., Stratum 1A, Phase 2 and Stratum 1B/1B-ASP: Diagnosis Patients must have either • First relapse of BCP-ALL post allogeneic HSCT • Second or greater relapsed or refractory BCP-ALL • Refractory disease, defined as newly diagnosed patients who are induction failures after at least 2 previous regimens without attainment of remission, or patients with refractory first relapse after 1 previous reinduction regimen without attainment of remission. AND must meet the following criteria: • Patients must have M2 or M3 marrow status (= 5% blasts by morphology) • The malignant clone needs to be CD22 surface antigen positive (in either the bone marrow or peripheral blood) by institutional standards as determined by the local immunophenotyping laboratory. • The first 6 patients (Stratum 1A only) must have M3 marrow status (= 25% blasts by morphology)., Stratum 2: Diagnosis Patients must have second or greater relapsed or refractory CD22-positive B-cell malignancy including but not limited to diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), Burkitt lymphoma, Burkitt leukemia or B-cell precursor lymphoblastic lymphoma: • There must be histologic verification of disease at original diagnosis or subsequent relapse. • Patient must have evaluable or measurable disease documented by radiographic criteria or bone marrow disease present at study entry. • The malignant cells need to be CD22 surface antigen positive (in either biopsy material, the bone marrow or peripheral blood) by institutional standards as determined by the local immunophenotyping laboratory., Stratum 3: Diagnosis • First BM or combined relapse of CD22+ VHR BCP-ALL defined as any relapse <18 months from initial diagnosis and/or cytogenetic-high risk characteristics: KTM2A/AF4, E2A/TCF3-PBX1 t(1;19) or E2A/TCF3-HLF t(17;19), hypodiploidy (less than 40 chromosomes), TP53 mutation and/or deletion, as also shown in Table 2 (excluding patients who received a HSCT in 1st CR). AND must meet the following criteria: • Patients must have M2 or M3 marrow status (= 5% blasts by morphology) • The malignant clone needs to be CD22 surface antigen positive (in either the bone marrow or peripheral blood) by institutional standards as determined by the local immunophenotyping laboratory. • Evidence of prior fusion gene abnormalities is acceptable as they tend to be stable during the course of the disease. • Laboratory techniques acceptable to test the presence of the above mentioned cytogenetic-high risk characteristics are chromosome banding analysis (CBA), FISH, PCR and/or Next Generation Sequencing (inclusion is based on local laboratory results)., For all patients Performance Level and Life Expectancy • Karnofsky > 60% for patients > 16 years
Isolated extramedullary relapse • Patients with isolated extramedullary disease are excluded (not applicable to lymphoma patients except for isolated CNS-relapse), VOD/SOS • Patients with any history of prior or ongoing VOD/SOS per the modified Seattle criteria are excluded, as specified in Appendix 3, or prior liver-failure [defined as severe acute liver injury with encephalopathy and impaired synthetic function (INR of =1.5)]., Infection • Patients will be excluded if they have a systemic fungal, bacterial, viral or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment. • The patient may not have: • A requirement for vasopressors; • Positive blood culture within 48 hours of study enrollment; • Fever above 38.2 degrees Celsius within 48 hours of study enrollment with clinical signs of infection. Fever that is determined to be due to tumor burden is allowed if patients have documented negative blood cultures for at least 48 hours prior to enrollment and no concurrent signs or symptoms of active infection or hemodynamic instability. • A positive fungal culture within 30 days of study enrollment. • Active fungal, viral, bacterial, or protozoal infection requiring IV or oral treatment. Chronic prophylaxis therapy to prevent infections is allowed., Other anti-cancer therapy • Patients will be excluded if there is a plan to administer non-protocol anti-cancer therapy including but not limited to chemotherapy, radiation therapy, or immunotherapy during the study period. • Patients will be excluded if they have received prior treatment with anti-tumor vaccines., Allergic reaction • Patients with prior Grade 3/4 allergic reaction to a monoclonal antibody are excluded., Concurrent disease • Patients will be excluded if they have significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance with protocol therapy, interfere with consent, study participation, follow up, or interpretation of study results. • Children with Down syndrome are excluded from participation in the dose finding parts (stratum 1A and 1B), but not in the single-agent phase 2 cohort or the VHR cohort., Additional exclusion criteria for Stratum 1B • Patients with grade 3-4 peripheral neuropathy (as defined in the Delphi consensus of acute toxic effects for childhood ALL by Schmiegelow et al.12). • Patients with prior history of thrombosis during steroid and/or asparaginase are eligible provided they use adequate anti-coagulant prophylaxis, according to institutional guidelines. • Patients in whom prior experience suggests that a timely delivery of therapy is unlikely or associated with an undue risk because of intolerance., Additional exclusion criteria for Stratum 1B-ASP cohort only • Patients with any history of PEG-asparaginase intolerance due to allergic reactions or silent inactivation during prior treatment. • Patients with any history of prior asparaginase-associated acute pancreatitis (any grade as defined in the Delphi consensus12. Patients who are excluded from Stratum 1B-ASP may potentially be enrolled in Stratum 1B expansion cohort., Additional exclusion criteria for Stratum 3 (VHR cohort) only • Patients who are transplanted in CR1 (such patients are eligible for the phase 1B cohort).
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method