E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
B-lineage (CD19 positive) ALL (B, pro-B, pre-B or c-ALL) refractory to standard treatment or with relapsed disease |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10024338 |
E.1.2 | Term | Leukemia lymphoblastic acute |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Part I: To determine the recommended dose of MOR00208 in pediatric patients on the basis of the maximum tolerated dose (MTD). Part II: To evaluate the time until hematological relapse (> 5% leukemic blasts) or increase of MRD ≥ 2 log in bone marrow during an observation time of 545 days accounting for competing risks. |
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E.2.2 | Secondary objectives of the trial |
Part I: 1. To evaluate the pharmacokinetics with measurement of plasma concentrations of MOR00208 2. Assessment of Safety of MOR00208 by NCI Common Toxicity Criteria, version 5.0. Part II: 1. To determine the rate of patients with "Success of treatment", defined as survival without newly emerging MRD or increasing MRD ≥ 2 log in bone marrow or peripheral blood or unacceptable toxicity/infections. 2. To evaluate the overall survival. 3. To evaluate changes in minimal residual disease during and after treatment in bone marrow aspirates with evaluation of the rate of patients with MRD reduction of at least 1 log at any time point compared to baseline. 4. To evaluate changes in peripheral B cell numbers by flow cytometry in peripheral blood until the end of follow-up. 5. To evaluate the cytotoxicity of patient derived PBMCs against cell lines (NALM) and cryopreserved autologous blasts. 6. Assessment of Safety of MOR00208 by NCI Common Toxicity Criteria, version 5.0. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age < 18 years at enrollment o only children ≥ 3 years at enrollment will be enrolled prior to the identification of the recommended Phase II dose (maximum tolerated dose, MTD) • B-lineage (CD19 positive) ALL (B, pro-B, pre-B or c-ALL) • Patients must have either underwent a first allogeneic stem cell transplantation with newly emerging or persistent MRD load posttransplant or have received stem cell transplantation without having reached a sufficient molecular remission prior to transplant (defined as MRD ≥10E-4) irrespective of MRD after SCT or underwent a second or subsequent allogeneic stem cell transplantation irrespective of MRD after SCT • Informed consent must be given by patients or legal representatives |
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E.4 | Principal exclusion criteria |
• Frank relapse (>5% leukemic blasts) • Philadelphia chromosome-positive (Ph+) ALL • Ejection fraction <25% on echocardiography • Cystatin C-clearance <40ml/min • Liver function abnormalities with bilirubin >4 mg/dL and elevation of transaminases higher than 400 U/L • Severe infection (HIV, Chronic active viral hepatitis), tests have to be conducted at screening • Acute GvHD III-IV or extensive chronic GvHD • The following immunosuppressive drugs (≥ 1 week of administration): steroids ≥ 1mg/kg body weight, cytostatics (except intrathecal/intracerebroventricular application for CNS treatment) • Application of other experimental therapy modalities in the last 4 weeks • Significant psychiatric disabilities, uncontrolled seizure disorders or severe peripheral neuropathy/ leukencephalopathy • Signs of autoimmune disease (i.e. idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia) • Subjects that do not agree to refrain from donating blood while on study drug • Concurrent severe or uncontrolled medical disease which by assessment of the treating physician could compromise participation in the study • Women during pregnancy and lactation • History of hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Recommended dose of MOR00208 in pediatric patients, determined on the basis of the maximum tolerated dose (MTD) 2. Time until hematological relapse (> 5% leukemic blasts) or increase of MRD ≥ 2 log in bone marrow during an observation time of 545 days accounting for competing risks. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. End of Part I. 2. Day 545. |
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E.5.2 | Secondary end point(s) |
- Pharmacokinetic of MOR00208 - Safety and toxicity of MOR00208 - Rate of patients with treatment success defined as survival without newly emerging MRD or increasing MRD ≥ 2 log in bone marrow or peripheral blood or unacceptable toxicity. - Overall survival. - Rate of patients with MRD reduction of at least 1 log at any time point compared to basline MRD measurement between SCT and start of study treatment. - B cell numbers at several time points. - Cytotoxicity of patient derived PBMCs against cell lines (NALM) and cryopreserved autologous blasts at several time points. - Safety and toxicity of MOR00208 Safety endpoints: • Any toxicity irrespective of grade • Number of Deaths • Number of Relapses • Adverse events will be presented in line listings and also in cumulative tabulations. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Day 365 for the rate of patients with treatment success. Day 545 for the other endpoints. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
First in pediatric patients. |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the study is defined as the completion of the trial report. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |