Clinical Trials Register

Summary
EudraCT Number:	2013-005240-28
Sponsor's Protocol Code Number:	PTCL-Dasa01
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2014-02-26
Trial 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

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2013-005240-28

A.3

Full title of the trial

OPEN LABEL, PHASE IIA MULTICENTER STUDY OF DASATINIB IN THE TREATMENT OF PATIENTS WITH PERIPHERAL T-CELL LYMPHOMA (PTCL) RELAPSED/REFRACTORY OR NOT AMENABLE TO CONVENTIONAL THERAPY-PTCL-DASA01

Studio di fase IIa in aperto, multicentrico sul ruolo di dasatinib nel trattamento di pazienti con linfoma a cellule T periferiche (PTCL) ricaduto/refrattario o non candidabile a terapia convenzionale

A.3.1

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

OPEN LABEL, PHASE IIA MULTICENTER STUDY OF DASATINIB IN THE TREATMENT OF PATIENTS WITH PERIPHERAL T-CELL LYMPHOMA (PTCL) RELAPSED/REFRACTORY OR NOT AMENABLE TO CONVENTIONAL THERAPY-PTCL-DASA01

A.4.1

Sponsor's protocol code number

PTCL-Dasa01

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	AOU di Bologna, Policlinico S.Orsola-Malpighi
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Bristol-Myers-Squibb S.r.l.
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	AOU di Bologna, Policlinico S.Orsola-Malpighi
B.5.2	Functional name of contact point	U.O.Ematologia (P.I. Pier Luigi Zin
B.5.3	Address:
B.5.3.1	Street Address	Via Massarenti 9
B.5.3.2	Town/ city	Bologna
B.5.3.3	Post code	40138
B.5.3.4	Country	Italy
B.5.4	Telephone number	00390516364042
B.5.5	Fax number	00390516364037
B.5.6	E-mail	pierluigi.zinzani@unibo.it

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	Yes
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DASATINIB
D.3.9.1	CAS number	302962-49-8
D.3.9.4	EV Substance Code	SUB23322
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	No
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

PATIENTS WITH PERIPHERAL T-CELL LYMPHOMA (PTCL)

pazienti con linfoma a cellule T periferiche (PTCL)

E.1.1.1

Medical condition in easily understood language

PATIENTS WITH PERIPHERAL T-CELL LYMPHOMA (PTCL)

pazienti con linfoma a cellule T periferiche (PTCL)

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutic techniques [E02]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.1
E.1.2	Level	PT
E.1.2	Classification code	10002230
E.1.2	Term	Anaplastic large cell lymphoma T- and null-cell types refractory
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Assessment of clinical responses in the clinical setting of relapsed/refractory peripheral T-cell lymphomas expressing PDGFRA.

Valutare le risposte cliniche nel setting clinico dei linfomi a cellule T periferiche che esprimono PDGFRA.

E.2.2

Secondary objectives of the trial

To asses safety and tolerability of dasatinib in the clinical setting of relapsed/refractory peripheral T-cell lymphomas expressing PDGFRA.
Identification of clinico-pathological correlates with treatment response.
Assessment of the clinical response duration and of patients’ survival

• Valutare la sicurezza e la tollerabilità di dasatinib nel setting clinico dei linfomi a cellule T periferiche che esprimono PDGFRA.
• Identificare le correlazioni clinico-patologiche con la risposta al trattamento.
• Valutare la durata della risposta clinica e la sopravvivenza dei pazienti.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients diagnosed of PTCL (any subtype according to the REAL/WHO classification), expressing PDGFRA, with one of the following:
a. have relapsed at least 1 month after conventional cytoreductive chemotherapy, or,
b. are refractory to at least 1 month of cytoreductive chemotherapy, or
c. are, for whatever reason, not considered candidates for therapy with conventional cytoreductive chemotherapy.
2. Not a candidate for allogeneic bone marrow transplantation.
3. ECOG Performance score of 0, 1, 2 or 3 (Karnofsky Performance Score >40%).
4. Life expectancy >4 weeks.
5. Adequate hepatic and renal function, as defined by serum transaminases <2.5x ULN, bilirubin <1.5x ULN, and creatinine <1.5x ULN.
6. Age 18 years or greater.
7. Women who are pregnant or breast feeding or women of childbearing potential (WOCBP) willing to use a double method of contraception during the study and 3 months after the end of treatment. One of these methods of contraception must be a barrier method. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months or had menses any time in the preceding 12 consecutive months. WOCBP must have a negative serum pregnancy test at baseline
8. Male patient whose sexual partner(s) are WOCBP who are willing to use a double method of contraception, one of which includes a condom, during the study and for 3 months after the end of treatment
9. Documentation of written informed consent to participate in the trial.
10. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.

• Pazienti con diagnosi di PTCL (qualsiasi sottotipo in accordo con la classificazione REAL/WHO), che esprimano PDGFRA e con almeno uno delle seguenti condizioni:
o Siano ricaduti almeno 1 mese dopo chemioterapia citoriduttiva o
o siano risultati refrattari a una chemioterapia citoriduttiva di almeno 1 mese o
o siano, per qualsiasi ragione, considerati non candidabili alle chemioterapia citoriduttiva convenzionale.
• Non candidabili per il trapianto di midollo osseo allogenico.
• ECOG performance status ≤3 (Karnofsky >40%).
• Aspettativa di vita >4 settimane.
• Funzioni renale ed epatica adeguate, definite da valori di transaminasi sieriche <2.5 ULN, bilirubina <1.5 ULN e creatinina < 1.5 ULN.
• Consenso informato scritto firmato.

E.4

Principal exclusion criteria

1. Lack of recovery from the acute toxic effects of previous chemotherapy (to CTCAE grade >1) with the exception of chemotherapy-induced alopecia.
2. Treatment with any investigational agent within 4 weeks prior to study therapy.
3. Major surgeries within 4 weeks from study start or not fully recovered from any previous surgical procedure.
4. Presence of any medical or psychiatric condition which may limit full compliance with the study or increase the risk associated with study participation or study drug administration, including but not limited to:
a. Presence of central nervous system (CNS) lymphoma.
b. Active uncontrolled bacterial infection.
c. Known human immunodeficiency virus (HIV) infection and/or known positivity for Hepatitis B (core) and/or HCV (patients who are negative by PCR are eligible).
d. Grade 3 or 4 bleeding.
e. Significant cardiovascular disease (i.e., uncontrolled arrhythmias, unstable angina), or a major thromboembolic event (myocardial infarction, stroke, transient ischemic attack, pulmonary embolism, or non-catheter-related deep-vein thrombosis) in the last 6 months.
f. Patients with known adrenal insufficiency.
g. Presence of any other incurable malignancy.
h. Pregnancy or breast-feeding.
i. Malabsorption syndromes.

Criteri di esclusione: (elencare)
1 . Mancanza di recupero dagli effetti tossici acuti della chemioterapia precedente (grado CTCAE > 1 ) con l'eccezione di alopecia indotta da chemioterapia .
2 . Il trattamento con qualsiasi farmaco sperimentale nelle 4 settimane precedenti alla terapia in studio .
3 . Interventi chirurgici maggiori entro 4 settimane dall'inizio studio o non completo recupero da una qualsiasi procedura chirurgica precedente.
4 . Presenza di qualsiasi condizione medica o psichiatrica che può limitare la piena aderenza alle procedure dello studio, aumentare il rischio associato alla partecipazione allo studio o aumentare il rischio relato alla somministrazione del farmaco in studio, ad esempio (elenco non esaustivo ) :
a . Presenza di un linfoma che interessa il sistema nervoso centrale ( SNC ) .
b . Infezione batterica incontrollata attiva .
c . Noto virus dell'immunodeficienza umana ( HIV) e / o positività nota per l'epatite B ( core) e / o HCV (i pazienti che sono negativi per PCR sono ammissibili ) .
d . Sanguinamento di grado 3 o 4.
a. e. Significativa malattia cardiovascolare ( ad esempio , aritmie non controllate , angina instabile ) , o un grande evento tromboembolico ( infarto miocardico, ictus , attacco ischemico transitorio , embolia polmonare , o trombosi venosa profonda non-catetere-relata ) negli ultimi 6 mesi.
f . I pazienti con nota insufficienza renale .
g . Presenza di qualsiasi altro tumore maligno incurabile .
h . Gravidanza o allattamento .
i. Sindromi da malassorbimento .

E.5 End points

E.5.1

Primary end point(s)

Assessment of clinical response in terms of complete remission, partial remission, stable disease

valutazione della risposta clinica in termini di tasso di risposte complete, remissioni parziali e malatta stabile

E.5.1.1

Timepoint(s) of evaluation of this end point

12 months

12 mesi

E.5.2

Secondary end point(s)

2. Assessment of toxicity in terms of type, frequency, severity, timing, and relatedness to the investigational treatment of adverse events (AE), by using the NCI CTCAE v 4.0 during the entire study period.
3. Assessment of clinico-pathological features related to treatment response assessed by gene expression profiling and gene sequencing.
4. Overall survival using Kaplan-Meier estimate (OS) at 12th month.
5. Progression free survival using Kaplan-Meier estimate (PFS) at 12th month

E.5.2.1

Timepoint(s) of evaluation of this end point

24 months

24 mesi

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

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

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

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

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

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

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

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2014-05-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-06-10

P. End of Trial
P.	End of Trial Status	Ongoing

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