Clinical Trials Register

Summary
EudraCT Number:	2011-002307-14
Sponsor's Protocol Code Number:	ICLL01
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-12-15
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

France - ANSM

A.2

EudraCT number

2011-002307-14

A.3

Full title of the trial

ICLL01 BOMP Study

Phase II salvage treatment with Bendamustine, Ofatumumab and MethylPrednisolone (BOMP) in relapsed B-cell chronic lymphocytic leukemia (B-CLL).

A.3.1

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

Phase II salvage treatment with Bendamustine, Ofatumumab and MethylPrednisolone (BOMP) in relapsed B-cell chronic lymphocytic leukemia (B-CLL).

Traitement de phase II par Bendamustine, Ofatumumab et MethylPrednisolone (BOMP) dans les leucémies lymphoïdes chroniques B (LLC-B) en rechute.

A.3.2

Name or abbreviated title of the trial where available

ICLL 01 BOMP study

A.4.1

Sponsor's protocol code number

ICLL01

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	Groupe Est Ouest des Leucémies et Autres Maladies du Sang
B.1.3.4	Country	France
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	Groupe Est Ouest des Leucémies et Autres Maladies du Sang
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Groupe Est Ouest des Leucémies et Autres Maladies du Sang
B.5.2	Functional name of contact point	DELEPINE Roselyne
B.5.3	Address:
B.5.3.1	Street Address	CHU Bretonneau Hématologie et Thérapie Cellulaire 2 bd Tonnellé
B.5.3.2	Town/ city	TOURS
B.5.3.3	Post code	37044
B.5.3.4	Country	France
B.5.4	Telephone number	+33247 47 37 98
B.5.5	Fax number	+ 33247 37 35 12
B.5.6	E-mail	r.delepine@chu-tours.fr

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.2.1.1.1	Trade name	Chlorhydrate de bendamustine
D.2.1.1.2	Name of the Marketing Authorisation holder	Astellas pharma GMBH
D.2.1.2	Country which granted the Marketing Authorisation	France
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	LEVACT 2,5 mg/ml powder for infusion
D.3.4	Pharmaceutical form	Powder 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	BENDAMUSTINE HYDROCHLORIDE
D.3.9.1	CAS number	3543-75-7
D.3.9.4	EV Substance Code	SUB00696MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2.5
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.IMP: 2
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.2.1.1.1	Trade name	Arzerra ®
D.2.1.1.2	Name of the Marketing Authorisation holder	Glaxo Group Ltd
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Ofatumumab
D.3.2	Product code	GSK 1841157
D.3.4	Pharmaceutical form	Concentrate and solvent for 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	OFATUMUMAB
D.3.9.1	CAS number	679818-59-8
D.3.9.4	EV Substance Code	SUB25221
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
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	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	Yes
D.3.11.13.1	Other medicinal product type	monoclonal antibody

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 B-cell chronic lymphocytic leukemia (B-CLL).

LLC B

E.1.1.1

Medical condition in easily understood language

relapsed B-cell chronic lymphocytic leukemia (B-CLL).

leucémies lymphoïdes chroniques B (LLC-B) en rechute

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

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	10003946
E.1.2	Term	B-Lymphocytic, CLL (Kiel Classification)
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

- Response rate (ORR, CR, PR) at 6 cycles of BOMP according to IWCLL 2008 guidelines

- taux de réponse après 6 cycles de BOMP

E.2.2

Secondary objectives of the trial

- Tolerance and safety of the BOMP regimen according to the CTC criteria
- Rate of achievement of a negative minimal residual disease (MRD) at 6 cycles of BOMP
- Survival including progression free survival (PFS), event free Survival (EFS), overall Survival (OS) and time to next treatment (TTNT)
- Impact of P53 mutation status/function/expression on response and survival

-Tolérance et sécurité du traitement BOMP

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Age superior to 18 years old and inferior to 80 years
2. Diagnosis of CLL according IWCLL 2008 criteria and fulfilling a Matutes- Moreau score ≥ 4
3. Relapsed or refractory CLL stage A, B or C with active disease requiring therapy according to IWCLL 2008 criteria
4. Relapse or refractory after 1 to 3 previous lines including at least one with fludarabine
5. ECOG Performans status and general condition.
• ECOG Performance status ≤ 2
• Fit Patients : CIRS Cumulative Illness Rating Scale)  6
• Life expectancy of more than 3 months

- patients with any rate 17p deletion
- patients candidate for of allogeneic transplantation, provided these patients will be planned to receive the full BOMP treatment and will have the final restaging
- patients fludarabine refractory
- patients with a prior diagnostic of CLL, who relapse without the criteria of a CLL, but with the criteria of a lymphocytic lymphoma
- prior monoclonal antibody (alemtuzumab or rituximab) exposure provided a washout period of 3 months prior to start of therapy.

E.4

Principal exclusion criteria

1. Untreated CLL
2. ECOG Performance Status > 2
3. Serious accompanying disorder or impaired organ function as indicated by:
- Abnormal renal function with creatinine clearance < 30 ml/min calculated according to the formula of Cockcroft and Gault
- Liver tests : total bilirubin >1.5 times UNL (unless due to CLL involvement of liver or a known history of Gilbert’s disease) transaminase (ALAT, ASAT) and/or alkaline phosphatase >2.5 times UNL (unless due to CLL involvement of liver)
- Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to randomization, congestive heart failure (NYHA III-IV), and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities.
- Severe chronic obstructive pulmonary disease with hypoxemia or pulmonary diffusion capacity < 40 %
- Uncontrolled diabetes mellitus,
- Uncontrolled hypertension
- History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae
- Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which in the opinion of the investigator may represent a risk for the patient.
4- CIRS (Cumulative Illness Rating Scale) > 6
5- Clinically significant auto-immune anemia : i.e. any drop in hemogolobin level related to an hemolytic autoimmune process attested by the following markers : elevated indirect bilirubin, elevated LDH, low haptoglobin levels, high reticulocytes count along with a positive direct anti-erythrocyte test (in ditrect test
6- Transformation to aggressive B-cell malignancy (e.g. diffuse large cell lymphoma, Hodgkin lymphoma, or prolymphocytic leukaemia)
7- Prior treatment with anti-CD20 monoclonal antibody or alemtuzumab within 3 months prior to start of therapy.
8- Prior autologous transplantation
9- Prior treatment with bendamustine and or ofatumumab
10- Active second malignancy currently requiring treatment (except basal cell carcinoma, in situ cervix carcinoma and incidental prostate carcinoma). Subjects who have been free of malignancy for at least 5 years are eligible.
11- Known HIV-positivity
12 Positive serology for

E.5 End points

E.5.1

Primary end point(s)

- Response rate (ORR, CR, PR) at 6 cycles of BOMP according to IWCLL 2008 guidelines

E.5.1.1

Timepoint(s) of evaluation of this end point

10-12 weeks after the day one of the 6th cycle of BOMP.

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

end of study treatment + 3 years Follow up

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

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)

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

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

First patient : january 2012
last patient : january 2015
last patient out of treatment : October 2015
End of observation time : October 2018
Duration of the entire trial= january 2012 to October 2018

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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

115

F.4.2

For a multinational trial

F.4.2.2

In the whole clinical trial

115

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)

patients Follow-up every 3 months during 2 years and every 6 months after

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

2012-02-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-04-05

P. End of Trial
P.	End of Trial Status	Completed

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