Inotuzumab ozogamicine in pediatric ALL patients
- Conditions
- pediatric CD22-positive relapsed/refractory Acute LymphoblasticLeukemiaMedDRA version: 21.0Level: LLTClassification code 10063625Term: Acute lymphoblastic leukemia recurrentSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2016-000227-71-GB
- Lead Sponsor
- Erasmus MC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 111
Age: Patients must be = 1 and < 18 years of age
Additional criteria for Stratum 1A and 1B:
•First 3 patients on dose level 1 must be 6-18 yrs.
•Then at least 2 additional patients must be enrolled from age 1-6 yrs at the same dose level.
•After this: subsequent dose levels may enroll patients aged 1-18 yrs.
•In case 2 younger patients are not yet recruited, patients aged 6-18yrs 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 1st relapsed BCP-ALL after allo-HSCT or 2nd or greater relapsed or refractory BCP-ALL, or refractory disease (after at least 2 prior regimens):
•M2 or M3 marrow status (= 5% blasts by morphology)
•CD22 surface antigen positive (either BM or PB)
•Stratum 1 only: The first 6 patients must have M3 marrow status (= 25% blasts by morphology).
Stratum 2: Diagnosis
Patients must have 2nd 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:
•Histologic verification of disease at original diagnosis or subsequent relapse
•Evaluable or measurable disease (by radiographic criteria or BM disease present)
• CD22 surface antigen positive (either biopsy material, BM or PB)
All Strata
Performance Level and Life Expectancy:
•Karnofsky > 60% for patients > 16 years of age and Lansky > 60% for
patients = 16 years of age.
•life expectancy of at least 6 weeks.
Prior Therapy:
Patients must have fully recovered from the acute toxic effects of all
prior chemotherapy, immunotherapy, or radiotherapy defined as
resolution of all such non-hematologic toxicities to = Grade 2 per the
CTCAE 4.03.
•Chemotherapy: At least 7 days wash-out; except for hydroxyurea, 6-mp
and steroids (wash-out 48 hrs) and intrathecal therapy (no wash-out).
Patients who relapse while receiving maintenance chemotherapy will not
be required to have a waiting period.
•Radiotherapy: At least 28 days must have elapsed since any prior
radiation therapy.
•Hematopoietic Stem Cell Transplant: At least 90 days must have
elapsed since previous allo-HSCT. No evidence of active GVHD; not
receiving GVHD prophylaxis or treatment.
•Hematopoietic growth factors: At least 7 days wash-out of therapy with
GCSF or other growth factors. At least 14 days wash-out of pegfilgrastim
(Neulasta®).
•Immunotherapy: At least 42 days wash-out of any type of
immunotherapy, e.g. CART therapy. No prior CD22-
targeted therapy or tumor vaccines permitted.
•Monoclonal antibodies: wash-out of at least 3 half-lives of the antibody
(ie: Rituximab = 66 days, Epratuzumab = 69 days), with the exclusion of
blinatumomab. Patients must have been off blinatumomab infusion for at
least 14 days and all drug-related toxicity must have resolved to grade 2
or lower.
•Investigational drugs: At least 7 days or 5 drug half-lives (whichever is
longer) must have elapsed since prior treatment with any experimental
drug (with the exception of monoclonal antibodies).
•no prior treatment with a calicheamicin-conjugated antibody (e.g.
gemtuzumab ozogamicin).
Renal and Hepatic Function:
•serum creatinine = 1.5 x ULN according to age. If the serum creatinine
is > than 1.5 xULN, the patient must have a radioisotope GFR =
70mL/min/1.73m2.
•AST and ALT = 2.5 x ULN.
•total bilirubin = 1.5 x ULN (unless pati
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 liverfailure
[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 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.
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.
•Patients with Down syndrome are excluded for the phase 1 dose finding
part (stratum 1A and 1B), but not in the stratum 1 phase 2 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.1 ). 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 consensus.1).
Patients who are excluded from Stratum 1B-ASP may potentially be enrolled in Stratum 1B expansion 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