Clinical Trials Register

Summary
EudraCT Number:	2012-003101-10
Sponsor's Protocol Code Number:	CD-ON-CAT-80151036
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-05-08
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2012-003101-10

A.3

Full title of the trial

A Phase 2, Multicenter, Single-arm Study of Moxetumomab Pasudotox in Pediatric Subjects with Relapsed or Refractory Pediatric Acute Lymphoblastic Leukemia (pALL) or Lymphoblastic Lymphoma of B-cell Origin

Studio di Fase 2, multicentrico, a braccio singolo di Moxetumomab Pasudotox in soggetti pediatrici affetti da leucemia linfoblastica acuta pediatrica (Pediatric Acute Lymphoblastic Leukemia, pALL) recidivante o refrattaria o da linfoma linfoblastico originato da cellule B

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A Phase 2, Multicenter Study in Pediatric Subjects with Relapsed or Refractory Pediatric Acute Lymphoblastic Leukemia (pALL) or Lymphoblastic Lymphoma

Studio di Fase 2, multicentrico, in soggetti pediatrici affetti da leucemia linfoblastica acuta pediatrica (Pediatric Acute Lymphoblastic Leukemia, pALL) recidivante o refrattaria o da linfoma linfoblastico

A.4.1

Sponsor's protocol code number

CD-ON-CAT-80151036

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	MedImmune, LLC
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	MedImmune, LLC
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	MedImmune, LLC
B.5.2	Functional name of contact point	Clinical Trial Enquiries
B.5.3	Address:
B.5.3.1	Street Address	One MedImmune Way
B.5.3.2	Town/ city	Gaithersburg, Maryland
B.5.3.3	Post code	20878
B.5.3.4	Country	United States
B.5.6	E-mail	clinicaltrialenquiries@medimmune.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Moxetumomab Pasudotox
D.3.2	Product code	CAT-8015
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Moxetumomab Pasudotox
D.3.9.1	CAS number	1020748-57-5
D.3.9.2	Current sponsor code	CAT-8015
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	0.85
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

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

Leucemia linfoblastica acuta pediatrica (Pediatric Acute Lymphoblastic Leukemia, pALL) recidivante o refrattaria o da linfoma linfoblastico originato da cellule B

E.1.1.1

Medical condition in easily understood language

Pediatric Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

Leucemia linfoblastica acuta pediatrica o linfoma linfoblastico

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

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

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)

Valutare l’efficacia misurata tramite la risposta completa composita (composite complete response, CRc)

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

• Valutare la sicurezza e la tollerabilità
• Valutare l'immunogenicità e la farmacocinetica
• La sopravvivenza senza progressione (Progression-free survival, PFS), la sopravvivenza complessiva (overall survival, OS),
la durata della risposta completa (duration of complete response, DOCR), la durata della risposta complessiva (duration of overall response, DOR).
• Tasso della malattia residua minima negativa come risposta completa composita (composite complete response, CRc)
• Numero elegibili per il trapianto di cellule staminali
• Il tasso di risposta complessivo (overall response rate, ORR)
• L'attività ematologica

E.2.3

Trial contains a sub-study

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.

I soggetti devono soddisfare tutti i seguenti criteri:
1) Età compresa tra ≥ 6 mesi < 18 ann.
2) Consenso informato scritto e assenso informato scritto (laddove previsto)
3) Presenza di ALL a cellule B o linfoma linfoblastico a cellule B
4) Malattia misurabile o valutabile.
5) Stato di malattia:
• i soggetti devono presentare malattia recidivante o refrattaria ed essere stati sottoposti ad almeno un trattamento chemioterapico standard e a un regime di salvataggio oppure a un trapianto allogenico di cellule staminali;
• in caso di recidiva successiva a pregresso HSCT allogenico, il periodo post-trapianto dei soggetti deve essere di almeno 3 mesi, i soggetti non devono presentare evidenze di malattia acuta da rigetto (GVHD, Graft versus Host Disease) in fase attiva e la terapia immunosoppressiva deve essere sospesa da almeno 4 settimane;
• gli effetti tossici acuti dovuti a pregressa chemioterapia prima dell’ingresso nello studio devono essere risolti a un grado ≤ 2, secondo l’opinione dello sperimentatore.
6) Per i soggetti non leucemici si richiede una conta assoluta dei neutrofili (ANC) > 1000/µl e una conta piastrinica > 50.000/mm2, a meno che un’eventuale citopenia non sia, a giudizio dello sperimentatore, dovuta a una patologia di base (ossia, potenzialmente reversibile con una terapia antineoplastica)..
7) Stato prestazionale adeguato
8) I soggetti con CNS 1 o 2 sono idonei solo in assenza di sintomi neurologici, come paralisi dei nervi cranici, indicativa di leucemia con interessamento del CNS.
9) I soggetti sessualmente attivi dovranno, per essere elegibili,acconsentire all’adozione di un metodo contraccettivo approvato oppure praticare l’astinenza.

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.

La presenza di una delle seguenti condizioni comporta l’esclusione del soggetto dalla partecipazione allo studio:
1) Qualsiasi stato che, secondo l’opinione dello sperimentatore, potrebbe interferire con la valutazione del prodotto sperimentale o con l’interpretazione dei risultati dello studio o dei risultati relativi alla sicurezza del soggetto.
2) Iscrizione concomitante ad un altro studio clinico, a meno che non si tratti di uno studio osservazionale non interventistico, oppure che il soggetto non si trovi nel periodo di follow-up di uno studio precedente, o non si ottenga la previa approvazione da parte dello sponsor.
3) I soggetti sono dipendenti del centro dello studio e direttamente coinvolti nella conduzione dello studio stesso presso il centro di iscrizione, oppure sono familiari diretti di un tale dipendente.
4) ALL testicolare isolata o con interessamento del CNS
5) Funzionalità epatica inadeguata.
6) Funzionalità renale inadeguata.
7) Linfoma del CNS rilevato all’esame radiologico.
8) Dati di laboratorio in linea con coagulazione intravascolare disseminata (CID) di grado ≥ 3 o eventuale CID di grado 2 non suscettibile di correzione.
9) Iperleucocitosi (definita come conta leucocitaria totale ≥ 50.000/μl) o malattia in rapida progressione che, nelle previsioni dello sperimentatore e dello sponsor, comprometterebbe la capacità di portare a termine la terapia prevista dallo studio.
10) Soggetti in stato di gravidanza o allattamento.
11) Pregresso trattamento con CAT-3888 (BL22), moxetumomab pasudotox o qualsiasi altro composto contenente esotossine di Pseudomonas.
12) Pregresso trattamento con terapia antineoplastica biologica nelle 2 settimane precedenti all’iscrizione incluse, ma non soltanto, terapie con anticorpi monoclonali o coniugati farmaco-anticorpo.
13) Chemioterapia sistemica ≤ 2 settimane (6 settimane in caso di nitrosouree) e radioterapia ≤ 3 settimane prima di avviare l’assunzione del farmaco in studio, fatta eccezione per i casi previsti dal protocollo.
14) Altri agenti antineoplastici sperimentali somministrati nei 30 giorni precedenti alla somministrazione della Dose 1, Ciclo 1 del farmaco in studio.
15) Sieropositività al virus dell’immunodeficienza umana (HIV).
16) Sieropositività per epatite B (HBsAg) o epatite C (anticorpi anti-HCV).
17) Dati oftalmologici clinicamente significativi emersi allo screening.
18) Patologia concomitante sintomatica non controllata che limiti la compliance ai requisiti dello studio.
19) Presenza di seconda malignità invasiva.
20) Qualsiasi condizione fisica, sociale o psichiatrica o di altro genere che, secondo l’opinione dello sperimentatore, impedirebbe la partecipazione o la cooperazione effettiva durante lo studio.
21) Infezione polmonare non controllata, presenza di edema polmonare.
22) Saturazione di ossigeno inadeguata.
23) Albumina sierica < 2 g/dl.
24) Radioimmunoterapia nei 2 anni precedenti alla data di arruolamento in studio.
25) Soggetto con anamnesi pregressa di microangiopatia trombotica o HUS.

E.5 End points

E.5.1

Primary end point(s)

Assess the efficacy defined as composite complete response (CRc)

Valutare l’efficacia misurata dalla risposta completa composita (composite complete response, CRc)

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

Le valutazioni della malattia saranno completate prima del primo ciclo e cicli successivi

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

• Valutare la sicurezza e la tollerabilità
• Valutare l'immunogenicità e la farmacocinetica
• sopravvivenza senza progressione (Progression-free survival, PFS), sopravvivenza complessiva (overall survival, OS),
durata della risposta completa (duration of complete response, DOCR), durata della risposta complessiva (duration of overall response, DOR).
• Tasso della malattia residua minima negativa come risposta completa composita (composite complete response, CRc)
• Numero elegibili per il trapianto di cellule staminali
• Risposta complessiva (overall response rate, ORR)
• Attività ematologica

E.5.2.1

Timepoint(s) of evaluation of this end point

Duration of study

Durata dello studio

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

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

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised