E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed or Refractory Pediatric Acute Lymphoblastic Leukemia (pALL) or Lymphoblastic Lymphoma of B-cell Origin |
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E.1.1.1 | Medical condition in easily understood language |
Pediatric Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma |
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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 | 14.1 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003939 |
E.1.2 | Term | B-lymphoblastic lymphoma (Kiel Classification) |
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 |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 or B-cell lymphoblastic lymphoma
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) For non-leukemic subjects, an absolute neutrophil count (ANC) > 1000/µL, and platelet count > 50,000/mm2 are required, unless cytopenias are judged by the investigator to be due to underlying disease (ie, potentially reversible with anti-neoplastic therapy).
7) Adequate Performance status.
8) Subjects with 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.
9) Sexually active subjects must agree to use an approved method of contraception or abstinence to meet eligibility criteria. |
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E.4 | Principal 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 study at the site of enrollment, or immediate family members of such individuals
4) Isolated testicular or CNS ALL
5) Inadequate hepatic function
6) Inadequate renal function
7) Radiologically-detected CNS lymphoma
8) Laboratory findings consistent with Grade ≥ 3 disseminated intravascular coagulation (DIC) or any Grade 2 DIC that does not correct
9) 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
10) Pregnant or breast-feeding females
11) Prior treatment with CAT-3888 (BL22), moxetumomab pasudotox, or any pseudomonas-exotoxin-containing compound
12) 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
13) Systemic chemotherapy ≤ 2 weeks (6 weeks for nitrosoureas) and radiation therapy ≤ 3 weeks prior to starting study drug with exceptions per protocol
14) Other investigational antineoplastic agents within 30 days prior to Cycle 1, Dose of study treatment
15) Human immunodeficiency virus (HIV) positive serology
16) Seropositivity for hepatitis B (HBsAg) or hepatitis C (HCV antibody)
17) Clinically significant ophthalmologic findings during the screening
18) Uncontrolled, symptomatic, intercurrent illness that would limit study compliance
19) Presence of a second invasive malignancy
20) Any physical, social, or psychiatric condition, or any other condition which in the opinion of the investigator would prevent effective study cooperation or participation
21) Uncontrolled pulmonary infection, presence of pulmonary edema
22) Inadequate oxygen saturation
23) Serum albumin < 2 g/dL
24) Radioimmunotherapy within 2 years prior to study enrollment
25) Subject with prior history of thrombotic microangiopathy or HUS. |
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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 | 5 |
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
|
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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
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 |