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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00426764




Registration number
NCT00426764
Ethics application status
Date submitted
23/01/2007
Date registered
25/01/2007
Date last updated
30/05/2019

Titles & IDs
Public title
A Trial of Romidepsin for Progressive or Relapsed Peripheral T-cell Lymphoma
Scientific title
A Phase II, Multicenter, Open-Label Trial Evaluating The Activity And Tolerability Of Romidepsin (Depsipeptide, FK228) In Progressive Or Relapsed Peripheral T-Cell Lymphoma Following Prior Systemic Therapy (GPI-06-0002)
Secondary ID [1] 0 0
2006-006228-21
Secondary ID [2] 0 0
GPI-06-0002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Peripheral T-cell Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Romidepsin

Experimental: Romidepsin - Participants received romidepsin 14 mg/m^2 administered intravenously over 4 hours on Days 1, 8, and 15 of a 28-day cycle. Participants continued on monthly cycles of romidepsin. The planned duration of study therapy was 6 cycles. Patients who responded could continue beyond 6 cycles until disease progression or other withdrawal criteria were met. For participants treated for 12 or more cycles, maintenance dosing (2 doses per cycle) was permitted.


Treatment: Drugs: Romidepsin
Romidepsin intravenously (through a vein) over 4 hours on Days 1, 8 and 15 of each 28-day cycle.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With a Complete Response According to the International Workshop Response Criteria (IWC) for Non-Hodgkin's Lymphomas (NHL) Assessed by an Independent Review Committee - Complete Response (CR): >75% decrease in size aggregate of nodal index lesions (large and small), complete disappearance of extranodal and non-index lesions; total disappearance of clinical disease including skin involvement; disease-related signs and symptoms, normalization of biochemical abnormalities and reduction in size of spleen or liver so no longer palpable. Unconfirmed CR: all above criteria except all nodal index lesions must have regressed >75% in the sum of the product diameters (SPD) from baseline. Individual nodes previously confluent must have regressed by >75% in their SPD.
Timepoint [1] 0 0
Response was assessed after every 2 cycles of treatment and at completion of therapy, up until 30 September 2012 (data cutoff for analysis). Maximum duration on study was 1931 days.
Secondary outcome [1] 0 0
Percentage of Participants With Objective Disease Response - Objective disease response was defined as patients with a Complete Response, Unconfirmed Complete Response or a Partial Response (PR) according to the IWC 1999 assessed by an independent review committee: CR, Cru defined above, PR defined as =50% decrease in size of 6 largest dominant nodes and/or nodal masses & extranodal index lesions and no increase of non-index lesions, liver, or spleen; no new sites of disease evident; skin lesions decreased by =50%.
Timepoint [1] 0 0
Response was assessed after every 2 cycles of treatment and at completion of therapy, up until 30 September 2012 (data cutoff for analysis). Maximum duration on study was 1931 days.
Secondary outcome [2] 0 0
Duration of Objective Disease Response - Duration of response was defined as the number of days from the date of the first disease response (Complete, Unconfirmed Complete or Partial Response) until the date of progression and was determined using Kaplan-Meier product-limit estimates. Progression was defined as: a =50% increase from the nadir in the individual sum of the products of the diameters of any index lesion; the reappearance of pathology, enlargement of liver/spleen, or unequivocal progression of non-measurable disease or appearance of any new lesions.
Timepoint [2] 0 0
Response was assessed after every 2 cycles of treatment and at completion of therapy, up until 30 September 2012 (data cutoff for analysis). Maximum duration on study was 1931 days.
Secondary outcome [3] 0 0
Duration of Complete Disease Response - Duration of response was defined as the number of days from the date of the first disease response (Complete or Unconfirmed Complete) until the date of progression and was determined using Kaplan-Meier product-limit estimates. Progression was defined as: a =50% increase from the nadir in the individual sum of the products of the diameters of any index lesion; the reappearance of pathology, enlargement of liver/spleen, or unequivocal progression of non-measurable disease or appearance of any new lesions.
Timepoint [3] 0 0
Response was assessed after every 2 cycles of treatment and at completion of therapy, up until 30 September 2012 (data cutoff for analysis). Maximum duration on study was 1931 days.
Secondary outcome [4] 0 0
Time to Disease Progression - Time to progression (=50% increase from the nadir in the individual sum of the products of the diameters of any index lesion; the reappearance of pathology, enlargement of liver/spleen, or unequivocal progression of non-measurable disease or appearance of any new lesions) was defined as the duration from the date of the first study drug dose to the date of relapse or progression as reported by the independent review committee and was determined using Kaplan-Meier product-limit estimates.
Timepoint [4] 0 0
Response was assessed after every 2 cycles of treatment and at completion of therapy, up until 30 September 2012 (data cutoff for analysis). Maximum duration on study was 1931 days.
Secondary outcome [5] 0 0
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status - The ECOG scale is as follows: Grade 0: Fully active, able to perform all pre-disease activities without restriction; Grade 1: Restricted in physically strenuous activity, ambulatory, able to carry out light work; Grade 2: Ambulatory and capable of all self-care but unable to work. Up and about more than 50% of waking hours; Grade 3: Capable of only limited self-care, confined to bed or chair > 50% of waking hours; Grade 4: Completely disabled. Cannot carry on any self-care. Confined to bed or chair. Data reported is the shift from Baseline ECOG score to best on-study assessment score.
Timepoint [5] 0 0
From Baseline up until 30 September 2012 (data cutoff for analysis). Maximum duration on study was 1931 days.
Secondary outcome [6] 0 0
Number of Participants With Treatment Emergent Adverse Events (TEAEs) - An adverse event or experience (AE) is defined as any untoward medical occurrence, which does not necessarily have to have a causal relationship with this treatment. A serious AE is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is an important medical event or condition. Related AEs are defined as those considered by the Investigator to have a possible, probable, or very likely/certain relationship to the study drug. AEs were graded as mild (1), moderate (2), severe (3), lifethreatening (4), or death (5). TEAEs occurred from the first dose of study medication through the end of the study (30 days post last dose) or any event that was present at baseline but worsened in intensity or was subsequently considered drug-related by the Investigator through end of study.
Timepoint [6] 0 0
From first dose of study treatment until the final study visit, which occurred 30 days after receiving the last dose. Mean duration of treatment up until 30 September 2012 (data cutoff for analysis) was 169 days.

Eligibility
Key inclusion criteria
Patients must fulfill all of the following criteria to be eligible for study participation
and have:

- Histologically confirmed PTCL not otherwise specified, angioimmunoblastic T-cell
lymphoma, extranodal natural killer (NK)/T-cell lymphoma nasal type, enteropathy- type
T-cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma, cutaneous ?d T-cell
lymphoma (excludes mycosis fungoides or Sezary syndrome), transformed mycosis
fungoides, hepatosplenic T-cell lymphoma, anaplastic large cell lymphoma (ALCL;
anaplastic lymphoma kinase [ALK]-1 negative), or patients with ALK 1 expressing ALCL
(ALK-1 positive) who have relapsed disease after autologous stem cell transplant
(ASCT);

- Age =18 years;

- Written informed consent;

- Progressive disease following at least one systemic therapy or refractory to at least
one prior systemic therapy;

- Measurable disease according to the International Workshop Response (IWC) criteria
and/or measurable cutaneous disease;

- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;

- Serum potassium =3.8 mmol/L and magnesium =0.85 mmol/L (electrolyte abnormalities can
be corrected with supplementation to meet inclusion criteria);

- Negative urine or serum pregnancy test on females of childbearing potential; and

- All women of childbearing potential must use an effective barrier method of
contraception (either an intrauterine contraceptive device [IUCD] or double barrier
method using condoms or a diaphragm plus spermicide) during the treatment period and
for at least 1 month thereafter. Male patients should use a barrier method of
contraception during the treatment period and for at least 1 month thereafter.
Hormonal methods of contraception such as the contraceptive pill or patch
(particularly those containing ethinyl-estradiol) should be avoided due to a potential
drug interaction.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients are ineligible for entry if any of the following criteria are met:

- Known central nervous system (CNS) lymphoma [computed tomography (CT) or magnetic
resonance imaging (MRI) scans are required only if brain metastasis is suspected
clinically];

- Chemotherapy or immunotherapy within 4 weeks of study entry (6 weeks if nitrosoureas
given);

- Initiation of corticosteroids during study (defined as 7 days prior to Cycle 1 Day
1[C1D1] until study drug discontinuation)

- Patients treated with a pulse of steroids were to discontinue steroid use 7 days
prior to C1D1 and have a repeat CT scan and disease assessment after
discontinuation of corticosteroids and before starting romidepsin;

- Concomitant use of any other anti-cancer therapy;

- Concomitant use of any investigational agent;

- Use of any investigational agent within 4 weeks of study entry;

- Any known cardiac abnormalities such as:

- Congenital long QT syndrome;

- QTc interval >480 milliseconds (msec);

- A myocardial infarction within 6 months of C1D1. Patients with a history of
myocardial infraction between 6 and 12 months prior to C1D1 who are asymptomatic
and have had a negative cardiac risk assessment (treadmill stress test, nuclear
medicine stress test, or stress echocardiogram) since the event may participate;

- Other significant electrocardiogram (ECG) abnormalities including 2nd degree
atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia
(ventricular rate less than 50 beats/min).

- Symptomatic coronary artery disease (CAD), e.g., angina Canadian Class II-IV. In
any patient in whom there is doubt, the patient should be referred to a
cardiologist for evaluation;

- An ECG recorded at screening showing significant ST depression (ST depression of
=2 mm, measured from isoelectric line to the ST segment at a point 60 msec at the
end of the QRS complex). If in any doubt, the patient should have a stress
imaging study and, if abnormal, angiography to define whether or not CAD is
present;

- Congestive heart failure (CHF) that meets New York Heart Association (NYHA) Class
II to IV definitions and/or ejection fraction <40% by MUGA scan or <50% by
echocardiogram and/or MRI;

- A known history of sustained ventricular tachycardia (VT), ventricular
fibrillation (VF), Torsade de Pointes, or cardiac arrest unless currently
addressed with an automatic implantable cardioverter defibrillator (AICD);

- Hypertrophic cardiomyopathy or restrictive cardiomyopathy from prior treatment or
other causes (if in doubt, see ejection fraction criteria above);

- Uncontrolled hypertension, i.e., blood pressure (BP) of =160/95; patients who
have a history of hypertension controlled by medication must be on a stable dose
(for at least one month) and meet all other inclusion criteria;

- Any cardiac arrhythmia requiring anti-arrhythmic medication;

- Serum potassium <3.8 mmol/L or serum magnesium <0.85 mmol/L (electrolyte abnormalities
can be corrected with supplementation to meet inclusion criteria);

- Concomitant use of drugs that may cause a significant prolongation of the QTc;

- Concomitant use of CYP3A4 significant or moderate inhibitors;

- Concomitant use of therapeutic warfarin or another anticoagulant due to a potential
drug interaction. Use of a small dose of a anticoagulant to maintain patency of venous
access port and cannulas is permitted;

- Clinically significant active infection;

- Known infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C;

- Previous extensive radiotherapy involving =30% of bone marrow (e.g., whole pelvis,
half spine), excluding patients who have had total body irradiation as part of a
conditioning regimen for ASCT;

- Major surgery within 2 weeks of study entry;

- Previous allogeneic stem cell transplant;

- Inadequate bone marrow or other organ function as evidenced by:

- Hemoglobin <9 g/dL (transfusions and/or erythropoietin are permitted);

- Absolute neutrophil count (ANC) =1.0 × 10^9 cells/L [patients with neutropenia
(ANC 1-1.5 10^9 cells/L) as a function of their disease may be supported with
granulocyte-colony stimulating factor (G-CSF)];

- Platelet count <100 × 10^9 cells/L or platelet count <75 × 10^9 cells/L if bone
marrow disease involvement is documented;

- Total bilirubin >2.0 × upper limit of normal (ULN) or >3.0 × ULN in the presence
of demonstrable liver metastases;

- Aspartate transaminase/serum glutamic oxaloacetic transaminase (AST/SGOT) and
alanine transaminase/serum glutamic pyruvic transaminase (ALT/SGPT) >2.0 × ULN or
>3.0 × ULN in the presence of demonstrable liver metastases; or

- Serum creatinine >2.0 × ULN;

- Patients who are pregnant or breast-feeding;

- Coexistent second malignancy or history of prior solid organ malignancy within
previous 3 years (excluding basal or squamous cell carcinoma of the skin, and in situ
carcinoma of the cervix (CIN 1) that has been treated curatively);

- Any prior history of a hematologic malignancy (other than T-cell lymphoma);

- Any significant medical or psychiatric condition that might prevent the patient from
complying with all study procedures; or

- Prior exposure to romidepsin (other histone deacetylase inhibitors are allowed).

Study design
Purpose of the study
Treatment
Allocation to intervention
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Mater Private Medical Centre - Haematology and Oncology Clinics of Australasia Research Centre - South Brisbane
Recruitment hospital [2] 0 0
Peter MacCallum Cancer Centre - East Melbourne
Recruitment hospital [3] 0 0
St. Vincent Hospital - Fitzroy
Recruitment hospital [4] 0 0
Royal North Shore Hospital - St Leonards
Recruitment postcode(s) [1] 0 0
4101 - South Brisbane
Recruitment postcode(s) [2] 0 0
3002 - East Melbourne
Recruitment postcode(s) [3] 0 0
3065 - Fitzroy
Recruitment postcode(s) [4] 0 0
2065 - St Leonards
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
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United States of America
State/province [4] 0 0
District of Columbia
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United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
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United States of America
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Illinois
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United States of America
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Kentucky
Country [9] 0 0
United States of America
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Maryland
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United States of America
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Massachusetts
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Michigan
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Minnesota
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Missouri
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United States of America
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Nebraska
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United States of America
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New Jersey
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United States of America
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New York
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United States of America
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Ohio
Country [18] 0 0
United States of America
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Oregon
Country [19] 0 0
United States of America
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Tennessee
Country [20] 0 0
United States of America
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Texas
Country [21] 0 0
United States of America
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Washington
Country [22] 0 0
Czechia
State/province [22] 0 0
Brno
Country [23] 0 0
Czechia
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Hradec Kralove
Country [24] 0 0
Czechia
State/province [24] 0 0
Prague 10
Country [25] 0 0
Czechia
State/province [25] 0 0
Prague 2
Country [26] 0 0
France
State/province [26] 0 0
Bordeaux
Country [27] 0 0
France
State/province [27] 0 0
Créteil
Country [28] 0 0
France
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Lille
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France
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Nantes
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France
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Paris
Country [31] 0 0
France
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Pessac
Country [32] 0 0
France
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Pierre Bénite
Country [33] 0 0
France
State/province [33] 0 0
Rennes
Country [34] 0 0
France
State/province [34] 0 0
Rouen Cedex
Country [35] 0 0
Germany
State/province [35] 0 0
Berlin
Country [36] 0 0
Germany
State/province [36] 0 0
Frankfurt a.M.
Country [37] 0 0
Germany
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Göttingen
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Germany
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Köln
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Germany
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Muenchen
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Germany
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Nürnberg
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Germany
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Tuebingen
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Poland
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Gdansk
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Poland
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Kraków
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Poland
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Lodz
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Poland
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Warszawa
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Pamplona
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Spain
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Salamanca
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Spain
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Santandar
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Sweden
State/province [51] 0 0
Lund
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Sweden
State/province [52] 0 0
Uppsala
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Ukraine
State/province [53] 0 0
Dnipropetrovsk
Country [54] 0 0
Ukraine
State/province [54] 0 0
Kyiv
Country [55] 0 0
Ukraine
State/province [55] 0 0
Lviv
Country [56] 0 0
United Kingdom
State/province [56] 0 0
London Hampstead
Country [57] 0 0
United Kingdom
State/province [57] 0 0
London
Country [58] 0 0
United Kingdom
State/province [58] 0 0
Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Celgene
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate the activity of romidepsin in patients with
progressive or relapsed peripheral T-cell lymphoma (PTCL) who have already been treated with
systemic therapy.
Trial website
https://clinicaltrials.gov/show/NCT00426764
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Myron Czuczman, MD
Address 0 0
Celgene
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications