E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pediatric Subjects with Relapsed or Refractory Pediatric Acute Lymphoblastic Leukemia (pALL) of B-cell Origin |
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E.1.1.1 | Medical condition in easily understood language |
Pediatric Acute Lymphoblastic Leukemia |
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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 | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000845 |
E.1.2 | Term | Acute lymphoblastic leukemia |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Assess the efficacy defined as Composite Complete Response (CRc) |
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E.2.2 | Secondary objectives of the trial |
• Assess safety and tolerability • Assess immunogenicity and pharmacokinetics • Progression-free survival (PFS), overall survival (OS), Duration of complete response (DOCR), Duration of overall response (DOR) • Minimal residual disease negative CRc rate • Number eligible for stem cell transplant • Overall response rate (ORR) • Hematologic activity |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria Subjects must meet all of the following criteria: 1) Between the ages of ≥ 6 months and < 18 years of age 2) Written informed consent and written informed assent (if applicable) 3) Must have histologically proven B-cell ALL with marrow involvement 4) Measurable or evaluable disease 5) Disease status: • Subjects must have relapsed or refractory disease and received at least 1 standard chemotherapy and either 1 salvage regimen or allogeneic HSCT. • In event of relapse after prior allogeneic HSCT, subjects must be at least 3 months post-transplant, have no evidence of active graft-vs-host disease, and been off immunosuppression for at least 4 weeks • Must have resolution of the acute toxic effects to ≤ Grade 2 from prior chemotherapy before entry, in the opinion of the investigator 6) Adequate Performance status. 7) Subjects with the following central nervous system (CNS) status 1 or 2 are eligible only in the absence of neurologic symptoms, such as cranial nerve palsy, suggestive of CNS leukemia. 8) Female subjects of childbearing potential and post-pubertal male subjects must agree to use an approved method of contraception for the study (if sexually active) or abstinence to meet eligibility criteria. |
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E.4 | Principal exclusion criteria |
Exclusion Criteria Any of the following would exclude the subject from participation in the study: 1) Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results 2) Concurrent enrollment in another clinical study, unless it is a non-interventional, observational study or the subject is in the follow-up period from a previous study, or prior sponsor approval is obtained 3) Employees of the study site directly involved with the conduct of the study at the site of proposed enrollment, or immediate family members of any such individuals 4) Isolated testicular or CNS ALL 5) Subjects with mixed-lineage leukemia (MLL) gene rearrangement 6) Inadequate hepatic function 7) Inadequate renal function 8) Radiologically-detected CNS lymphoma 9) Laboratory findings or clinical evidence consistent with Grade ≥ 3 disseminated intravascular coagulation (DIC) or any Grade 2 DIC that does not correct 10) Hyperleukocytosis (WBC ≥ 50,000/μL) or rapidly progressive disease that in the estimation of the investigator and sponsor would compromise ability to complete study therapy 11) Pregnant or breast-feeding females 12) A QTcF interval (manually overread) of ≥ 481 msec (ie, ≥ Grade 2) confirmed by medically qualified staff on at least 2 separate electrocardiograms (ECGs) performed at least 5 min apart within 28 days prior to enrollment 13) Prior treatment with CAT-3888 (BL22), moxetumomab pasudotox, or any pseudomonas-exotoxin-containing compound 14) Prior treatment with any anticancer biologic therapy within 2 weeks prior to enrollment, including but not limited to therapeutic monoclonal antibodies or antibody-drug conjugates 15) Systemic chemotherapy ≤ 2 weeks (6 weeks for nitrosoureas) and radiation therapy ≤ 3 weeks prior to starting study drug with exceptions per protocol 16) Other investigational antineoplastic agents within 30 days prior to Cycle 1, Dose of study treatment 17) Seropositivity for Human immunodeficiency virus (HIV) 18) Seropositivity for hepatitis B (HBsAg) or hepatitis C (HCV antibody) 19) Clinically significant ophthalmologic findings (evidence of retinal damage or injury) during the screening 20) Uncontrolled, symptomatic, intercurrent illness including, but not limited to infection, congestive heart failure, cardiac arrhythmia, malaria infection or any other condition that would limit compliance with study requirements 21) Presence of a second invasive malignancy 22) Any physical, social, or psychiatric condition, or any other condition which in the opinion of the principal investigator or designee would prevent effective study cooperation or participation in the study 23) Uncontrolled pulmonary infection, presence of pulmonary edema 24) Inadequate oxygen saturation 25) Serum albumin < 2 g/dL 26) Radioimmunotherapy within 2 years prior to enrollment in study 27) Subject with prior history of thrombotic microangiopathy or HUS. 28) Previous life-threatening anaphylactic reactions to prior monoclonal antibody-based immunotherapy or any component of the moxetumomab pasudotox formulation 29) T-cell ALL or T-cell lymphoblastic lymphoma 30) History of known congenital hypercoaguable condition 31) Subjects receiving high-dose estrogen therapy 32) For German Investigative Sites: Subjects with B-cell lymphoblastic lymphoma will be excluded.
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E.5 End points |
E.5.1 | Primary end point(s) |
Assess the efficacy defined as composite complete response (CRc) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Disease assessments will be completed prior to the first cycle and subsequent cycles |
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E.5.2 | Secondary end point(s) |
• Assess safety and tolerability • Assess immunogenicity and pharmacokinetics • PFS, OS, DOCR, DOR • Minimal residual disease negative CRc rate • Number eligible for stem cell transplant • ORR • Hematologic activity |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
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) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 29 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
France |
Germany |
Italy |
Netherlands |
Spain |
United Kingdom |
United States |
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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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12 months after last subject begins treatment or earlier if interim analysis performed after enrollment of the first 33 evaluable subjects shows CRc ≤ 21% |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 9 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 9 |