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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: Netherlands Trial Register
Last refreshed on: 24 February 2020
Main ID:  NTR5736
Date of registration: 31/03/2016
Prospective Registration: Yes
Primary sponsor: ErasmusMC, Rotterdam
Public title: Inotuzumab Ozogamicin for pediatric CD22-positive relapsed/refractory ALL
Scientific title: A phase I/II study of Inotuzumab Ozogamicin as a single agent and in combination with chemotherapy for pediatric CD22-positive relapsed/refractory Acute Lymphoblastic Leukemia
Date of first enrolment: 01/07/2016
Target sample size: 96
Recruitment status: Recruiting
URL:  https://trialregister.nl/trial/5629
Study type:  Interventional
Study design:  Randomized: No, Masking: None, Control: Not applicable, Group: undefined, Type: Single arm  
Phase: 
Countries of recruitment
The Netherlands
Contacts
Name: C.M.  Zwaan
Address: 
Telephone: +31 10 703 66 91
Email: c.m.zwaan@erasmusmc.nl
Affiliation: 
Name: C.M.  Zwaan
Address: 
Telephone: +31 10 703 66 91
Email: c.m.zwaan@erasmusmc.nl
Affiliation: 
Key inclusion & exclusion criteria
Inclusion criteria: Age
Patients must be ≥ 1 and < 18 years of age at the time of enrollment.
• 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 to less than 18 years may continue to be enrolled at dose level 1 until a maximum of 6 patients are enrolled.

Stratum 1A: Diagnosis
Patients must have either second or greater relapsed or refractory BCP-ALL, or refractory disease as defined below, 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 must have M3 marrow status (≥ 25% blasts by morphology).
• Refractory is 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.

Phase 2 Cohort: Diagnosis
Patients must have either second or greater relapsed or refractory BCP-ALL, or refractory disease as defined below, 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 must have M3 marrow status (≥ 25% blasts by morphology).
• Refractory is 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.

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.

Performance Level and Life Expectancy
• Karnofsky > 60% for patients > 16 years of age and Lansky > 60% for patients ≤ 16 years of age. (See Appendix I for Performance Scales).
• Patient must have a 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 prior to entering this study, with the exception of the authorized laboratory a

Exclusion criteria: 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.


Age minimum:
Age maximum:
Gender:
Health Condition(s) or Problem(s) studied
pediatric CD22-positive relapsed / refractory Acute Lymphoblastic Leukemia
Intervention(s)
A course of therapy is defined as 3 doses of InO administered weekly on days 1, 8 and 15. Course 1 will last 22 days (with delays allowed up to 42 days, depending on response and recovery from toxicity), and all subsequent courses will last 28 days, again with delays up to 42 days.
In addition to InO they will receive Anti-emetics and Methylprednisolone on day 1,8 and 15 and intrathecal MTX at day 1.
Patients will receive up to 6 cycles of treatment. Disease evaluation will take place after each course.
Primary Outcome(s)
In stratum 1A: Dose-limiting toxicities (DLTs) during the first course of therapy.

In phase 2 cohort: Overall Response Rate, measured as best response during InO treatment

Stratum 2: Safety and tolerability
Secondary Outcome(s)
In stratum 1A: Safety and tolerability, Measures of anti-leukemic activity, Serum pharmacokinetic parameters of InO and unconjugated calicheamicin, Pharmacodynamic parameters.

Phase 2 cohort: safety, other measures of anti-leukemic activity, Serum pharmacokinetic parameters of InO and unconjugated calicheamicin, Pharmacodynamic parameters.

Stratum 2: Measures of anti-tumor activity, Serum pharmacokinetic parameters of InO and unconjugated calicheamicin
Secondary ID(s)
Source(s) of Monetary Support
o.a. Pfizer
Secondary Sponsor(s)
Ethics review
Status:
Approval date:
Contact:
Results
Results available:
Date Posted:
Date Completed:
URL:
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