The safety and efficacy of the medicine Inotuzumab Ozogamicin in children with relapsed/refractory acute lymphatic leukemia (ALL)
- Conditions
- pediatric CD22-positive relapsed/refractory Acute Lymphoblastic LeukemiaMedDRA 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-DE
- Lead Sponsor
- Erasmus Medical Center
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 156
Age for all strata (Str1A, ph2, Str1B, Str2 and Str3): Patients must be =
1 and < 18 years of age
Patients with Down syndrome are excluded in Stratum 1A and 1B/1BASP
but not in the phase 2 cohort and Stratum 3
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)
Str3: diagnosis:
• 1st 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
• excluding patients transplanted in 1st CR.
• M2 or M3 marrow status (= 5% blasts by morphology)
• CD22 surface antigen positive (in either the BM or PB)
• Evidence of prior fusion gene abnormalities is acceptable
• cytogenetic-high risk characteristics determined by chromosome
banding analysis (CBA), FISH, PCR and/or Next Generation Sequencing
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: w
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 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 in the dose finding
parts (stratum 1A and 1B), but not in the phase 2 cohort or 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.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.
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