Clinical Trials Register

Summary
EudraCT Number:	2019-001381-14
Sponsor's Protocol Code Number:	VS-0145-229
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2019-09-19
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

UK - MHRA

A.2

EudraCT number

2019-001381-14

A.3

Full title of the trial

A Phase 2, Randomized, Open-label, 2-Arm Study Comparing 2 Intermittent Dosing Schedules of Duvelisib in Subjects with Indolent Non-Hodgkin Lymphoma (iNHL)

A.3.2

Name or abbreviated title of the trial where available

A Phase 2 Study of Intermittent Dosing Schedules of Duvelisib in Indolent Non-Hodgkin Lymphoma(iNHL)

A.4.1

Sponsor's protocol code number

VS-0145-229

A.5.4

Other Identifiers

Name:

IND

Number:

112,486

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	Verastem, Inc.
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	Verastem, Inc.
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	Verastem, Inc.
B.5.2	Functional name of contact point	Gloria Patrick
B.5.3	Address:
B.5.3.1	Street Address	117 Kendrick St., Suite 500
B.5.3.2	Town/ city	Needham, MA
B.5.3.3	Post code	02494
B.5.3.4	Country	United States
B.5.6	E-mail	gpatrick@verastem.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	Yes
D.2.5.1	Orphan drug designation number	EU/3/13/1157
D.3 Description of the IMP
D.3.1	Product name	Duvelisib
D.3.2	Product code	IPI-145
D.3.4	Pharmaceutical form	Capsule, hard
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	DUVELISIB
D.3.9.1	CAS number	1386861-49-9
D.3.9.2	Current sponsor code	IPI-145
D.3.9.4	EV Substance Code	SUB180102
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	15
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	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/13/1157
D.3 Description of the IMP
D.3.1	Product name	Duvelisib
D.3.2	Product code	IPI-145
D.3.4	Pharmaceutical form	Capsule, hard
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	DUVELISIB
D.3.9.1	CAS number	1386861-49-9
D.3.9.2	Current sponsor code	IPI-145
D.3.9.4	EV Substance Code	SUB180102
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	25
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

Indolent Non-Hodgkin Lymphoma (iNHL)

E.1.1.1

Medical condition in easily understood language

iNHL is a form of cancer that starts in white blood cells called lymphocytes part of body's immune system. This cancer grows and spreads slowly, often without symptoms. Men and women can develop it.

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	20.0
E.1.2	Level	HLT
E.1.2	Classification code	10029621
E.1.2	Term	Non-Hodgkin's lymphomas unspecified histology indolent
E.1.2	System Organ Class	100000004851

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

Evaluate the efficacy of duvelisib administered with prescribed drug holidays in subjects with iNHL (based on Cheson 2007)

E.2.2

Secondary objectives of the trial

- Evaluate supportive efficacy measures of duvelisib administered with prescribed drug holidays in subjects with iNHL (Based on Cheeson 2014);
- Evaluate the safety and tolerability of duvelisib administered with prescribed drug holidays in subjects with iNHL;
- Characterize the pharmacokinetics (PK) of duvelisib and metabolite(s) when duvelisib is
administered with prescribed drug holidays in subjects with iNHL;
EXPLORATORY OBJECTIVES :
- Evaluate Quality of Life (QoL) in subjects with iNHL treated with duvelisib with prescribed drug holidays;
- Evaluate potential biomarkers of clinical efficacy and/or safety of duvelisib administered with prescribed drug holidays in subjects with iNHL

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female subjects ≥ 18 years of age
2. Histologically confirmed diagnosis of iNHL. Histologic subtypes include FL Grades 1 to 3a, marginal zone lymphoma (splenic, nodal, or extranodal), or SLL.
3. Must have received at least 1 prior systemic regimen for iNHL
4. Must have documented radiologic evidence of disease progression, and at least 1 Bidimensionally measurable lesion ≥ 1.5 cm (which has not been previously irradiated), according to 2007 revised IWG criteria (Cheson 2007)
5. Must have adequate organ function defined by the following laboratory parameters:
a. Absolute neutrophil count (ANC) ≥ 1.0 × 109/L
b. Platelet count ≥ 75 × 109/L
c. Serum creatinine < 2.0 mg/dL (197 μmol/L)
d. Total bilirubin ≤ 1.5 × upper limit of normal (ULN) (exception: subjects with Gilbert's Syndrome may have a bilirubin > 1.5 × ULN)
e. Aspartate transaminase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum pyruvic transaminase (SGPT) ≤ 3.0 × ULN
6. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
7. Willingness of male and female subjects of reproductive potential (i.e., not surgically sterile or female subjects who are not postmenopausal) to use effective methods of contraception (see Section 10.4) for the duration of the study intervention and for 3 months after the last dose of duvelisib
8. Negative serum human chorionic gonadotropin (hCG) pregnancy test within 7 days before first dose of study intervention if the subject is a woman of childbearing potential (WCBP) (defined in Section 10.4)
9. Signed and dated institutional review board (IRB)/independent ethics committee (IEC)-approved informed consent form before any study specific-screening procedures are performed

E.4

Principal exclusion criteria

1. Anticancer treatment, major surgery, or use of any investigational drug within 28 days before the start of study intervention; palliative radiation therapy is allowed if > 7 days before planned first dose of study interventions and any toxicity is Grade ≤ 1.
2. Clinical or histological evidence of transformation to a more aggressive subtype of Lymphoma or grade 3b FL or Richter’s transformation or CLL
3. Received prior allogeneic hematopoietic stem cell transplant (HSCT)
4. Previous treatment with a PI3K inhibitor
5. Known hypersensitivity to duvelisib and/or its excipients
6. History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function
7. Prior history of drug-induced colitis or drug-induced pneumonitis
8. History of tuberculosis treatment within the 2 years prior to randomization
9. Administration of a live or live attenuated vaccine within 6 weeks of randomization
10. Ongoing treatment with chronic immunosuppressants (e.g., cyclosporine) or systemic steroids > 20 mg of prednisone (or equivalent) per day
11. Ongoing treatment for systemic bacterial, fungal, or viral infection at screening
• Note: Subjects on antimicrobial, antifungal, or antiviral prophylaxis are not specifically excluded if all other inclusion/exclusion criteria are met
12. Active cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection (i.e., subjects with detectable viral load)
13. Unable to receive prophylactic treatment for pneumocystis, herpes simplex virus (HSV), or herpes zoster (VZV) at screening
14. Infection with hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or human T-lymphotropic virus type 1
• Subjects with a positive hepatitis B surface antigen [HBsAg] or hepatitis C antibody [HCV Ab] will be excluded
• Subjects with a positive hepatitis B core antibody (HBcAb) must have negative hepatitis B virus (HBV) deoxyribonucleic acid (DNA) to be eligible, must receive prophylaxis with entecavir (or equivalent) concomitant with duvelisib treatment, and must be periodically monitored for HBV reactivation by institutional guidelines
• Investigators who strongly believe that a positive HBcAb is false due to passive immunization from previous immunoglobulin infusion therapy should discuss the potential to defer HBV prophylaxis with the Medical Monitor
15. Concurrent administration of medications or foods that are strong inhibitors or inducers of cytochrome P450 3A (CYP3A). No prior use within 2 weeks before the start of study intervention.
16. Subjects with clinically significant medical condition of malabsorption, inflammatory bowel disease, chronic conditions which manifest with diarrhea, refractory nausea, vomiting, or any other condition that will interfere significantly with drug absorption
17. Central nervous system non-Hodgkin lymphoma (NHL); lumbar puncture not required unless central nervous system involvement is clinically suspected
18. Baseline QTcF > 500 ms (average of triplicate readings). NOTE: This criterion does not apply to subjects with a right or left bundle branch block (BBB).
19. Concurrent active malignancy other than non-melanoma skin cancer or carcinoma in situ of the cervix, bladder cancer, or prostate cancer not requiring treatment. Subjects with previous malignancies are eligible if they have been disease-free for 2 years or more.
20. History of chronic liver disease, veno-occlusive disease/sinusoidal obstruction syndrome, alcohol abuse, or illicit drug use
21. History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months prior to first dose of study intervention
22. Unstable or severe uncontrolled medical condition (e.g., unstable cardiac function, unstable pulmonary condition). Any important medical illness or abnormal laboratory finding that would, in the Investigator’s judgment, increase the subject’s risk to participating in this study.
23. Female subjects who are pregnant or breastfeeding

E.5 End points

E.5.1

Primary end point(s)

Overall Response Rate (ORR) according to the 2007 revised International Working Group (IWG) Criteria (Cheson 2007)

E.5.1.1

Timepoint(s) of evaluation of this end point

ORR by Cheson 2007 (IWG criteria): 36 months

E.5.2

Secondary end point(s)

• ORR according to 2014 Lugano criteria (Cheson 2014) Note: all additional secondary response endpoints as well as progression-free survival (PFS), will be assessed separately using 2007 revised IWG criteria (Cheson 2007) and 2014 Lugano criteria (Cheson 2014)
• ORR, at 6, 12, 18, and 24 months after first dose of study intervention
• Progression-free Survival
• Time to Treatment Failure (TTF)
• Duration of Response (DOR)
• Overall Survival (OS)
• Lymph Node Response Rate (LNRR)
• Time to the First Response (TTFR)
• Adverse events (AEs), serious AEs (SAEs), vital signs, physical exams, and clinical laboratory values
• PK parameters for duvelisib and metabolite(s)
EXPLORATORY END POINTS
• Eastern Cooperative Oncology Group (ECOG) Performance Score
• EQ-5D-3L questionnaire responses, Blood assessments of immune cell populations, chemokines, cytokines, phosphorylated proteins, and/or circulating tumor ctDNA
• Fecal assessments of protein, DNA, and or RNA
• Tumor biopsy evaluation of biomarkers such as gene and copy number variation, RNA
expression, protein expression, and/or immune cell content

E.5.2.1

Timepoint(s) of evaluation of this end point

ORR by Cheson 2014 ( Lugano criteria) at 6, 12, 18 and 34 months: 36 months
PFS by Cheson 2007: 5 years
TTF: 5 years
DOR 5 years
OS: 5 years
LNRR: 36 months
TTFR: 36 months
Safety: 36 months
PK: 36 months

Exploratory
ECOG: 5 years
EQ-5D-3L: 5 years
Biomarkers: 5 years

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

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

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

Yes

E.8.1.2

Open

Yes

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.8.2.4

Number of treatment arms in the trial

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

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

Czech Republic

France

Germany

Italy

Korea, Republic of

Poland

Russian Federation

Spain

United Kingdom

United States

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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial 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.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

102

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)

Subjects receiving clinical benefit may continue receiving treatment even if the study has either met the primary endpoint or has followed the last randomized subject for 5 years, whichever is later. If the study is ended prior to all subjects discontinuing treatment, any subject continuing to receive benefit will be provided the opportunity to continue to receive duvelisib. Long-term treatment will be provided either in a separate clinical study or EAP consistent with local
regulations.

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

2019-11-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-01-15

P. End of Trial
P.	End of Trial Status	GB - no longer in EU/EEA

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