Phase 2 study to evaluate efficacy and safety of PQR309 in patients with relapsed or refractory lymphoma

• Register: EUCTR
• Last refreshed on: 8 August 2016
• Main ID: EUCTR2014-005384-33-DE
• Date of registration: 08/06/2015
• Prospective Registration: Yes
• Primary sponsor: PIQUR Therapeutics AG
• Public title: Phase 2 study to evaluate efficacy and safety of PQR309 in patients with relapsed or refractory lymphoma
• Scientific title: Open-Label, Non-randomized Phase 2 study with Safety Run-in Evaluating Efficacy and Safety of PQR309 in Patients with Relapsed or Refractory Lymphoma
• Date of first enrolment: 04/08/2015
• Target sample size: 72
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-005384-33
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Bosnia and Herzegovina, France, Germany, Israel, Serbia, Switzerland, United Kingdom, United States

Contacts

• Name: Chief Development Officer
• Affiliation: PIQUR Therapeutics AG

• Name: Chief Development Officer
• Affiliation: PIQUR Therapeutics AG

Key inclusion & exclusion criteria

Inclusion criteria:
1. Histologically confirmed diagnosis* of relapsed or refractory lymphoma, received at least two prior lines of therapy including immuno-chemotherapy. Patients with relapsed Chronic Lymphoid Leukemia (CLL) are eligible if they have received one or more prior lines of any standard therapy.
* archival biopsies may be used if obtained up to a year prior to enrollment; re-biopsy is strongly recommended if last biopsy was obtained more than a year ago.
2. Only for patients in the phase 2 part: At least one measurable nodal or extra-nodal lesion defined as follows: Clearly measurable (i.e., well-defined boundaries) in at least two perpendicular dimensions on imaging scan, or lymph node or nodal mass bi-dimensional measurement with > 1.5 cm in longest transverse diameter.
3. Age = 18 years.
4. Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-1.
5. Adequate organ system functions defined as follows:
a. Absolute neutrophil count (ANC) =1.0x10^9/l
b. Platelets = 75x10^9/l
c. Haemoglobin = 85g/L
d. Adequate hepatic function, defined as total bilirubin = 1.5 times the upper limit of normal (ULN) and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 times ULN (or ALT/AST = 5 times ULN in patients with liver involvement)
e. Adequate renal function, defined as serum creatinine = 1.5 times ULN
f. Fasting glucose <7.0 mmol/l; Glycated haemoglobin (HbA1c) <6.4%.
6. Ability and willingness to swallow and retain oral medication.
7. Willingness and ability to comply with the trial procedures.
8. Female and male patients with reproductive potential must agree to use effective contraception from screening until 90 days after discontinuation of PQR309.
9. Signed informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 36
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 36

Exclusion criteria:
1. Immunosupression due to:
-Allogeneic hematopoietic stem cell transplant (HSCT)
-Any immune-supressive therapy within 4 weeks prior to trial treatment start
-Known HIV infection.
2. Autologous stem cell transplant within 3 months prior to trial treatment start.
3. Concomitant anticancer therapy (e.g. chemotherapy, radiotherapy, hormonal therapy, immunotherapy, biological response modifier, signal transduction inhibitors).
4. Concomitant treatment with medicinal products that increase the pH (reduce acidity) of the upper gastrointestinal tract, including, but not limited to, proton-pump inhibitors (e.g. omeprazole), H2-antagonists (e.g. ranitidine) and antacids. Patients may be enrolled in the study after a wash-out period sufficient to terminate their effect.
5. Use of any investigational drug within 21 days prior to trial treatment start.
6. Patients who experienced National Cancer Institute (NCI) Common Terminology Criteria For Adverse Events (CTCAE) = Grade 3 on PI3K/mTOR inhibitors.
7. Any major surgery, chemotherapy or immunotherapy within 21 days prior to trial treatment start.
8. Symptomatic or progressing Central Nervous System (CNS) involvement. Exception: Patients with meningeal involvement can be included upon discussion between the sponsor and the investigator.
9. Persisting toxicities NCI CTCAE =2 related to prior anticancer therapy.
10. Presence of gastrointestinal disease or any other condition that could interfere significantly with the absorption of the study drug.
11. Severe/unstable angina, myocardial infarction or coronary artery bypass within the last 3 years prior to trial treatment start, symptomatic congestive heart failure New York Heart Association (NYHA) Class 3 or 4, hypertension BP>150/100mmHg.
12. A serious active infection at the time of treatment, or another serious underlying medical condition that could impair the ability of the patient to receive treatment.
13. Lack of appropriate contraceptive measures (male and female).
14. Pregnant or lactating women.
15. Known HIV infection.
16. Significant medical conditions which could jeopardize compliance with the protocol.
17. Uncontrolled diabetes mellitus; patients with controlled diabetes may be enrolled (see fasting glucose and HbA1c levels in inclusion criteria).


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Relapsed or refractory lymphoma
MedDRA version: 18.1 Level: PT Classification code 10025310 Term: Lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: PQR309
Product Code: PQR309
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Not available yet
CAS Number: 1225037-39-7
Current Sponsor code: PQR309
Other descriptive name: 5-(4,6-di-4-morpholinyl-1,3,5-triazin-2-yl)-4-(trifluoromethyl)-2-pyridinamine
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Product Name: PQR309
Product Code: PQR309
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Not available yet
CAS Number: 1225037-39-7
Current Sponsor code: PQR309
Other descriptive name: 5-(4,6-di-4-morpholinyl-1,3,5-triazin-2-yl)-4-(trifluoromethyl)-2-pyridinamine
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 80-

Primary Outcome(s)

Secondary Objective: To evaluate safety and pharmacokinetics of PQR309 in patients with relapsed or refractory lymphoma.

Main Objective: To evaluate the clinical efficacy of PQR309 in patients with relapsed or refractory lymphoma.

Primary end point(s): Efficacy of PQR309 in patients with relapsed or refractory lymphoma according to Cheson Criteria.

Timepoint(s) of evaluation of this end point: Radiological lymphoma evaluation will be performed at baseline (within 28 days prior to first PQR309 intake) and during treatment at the following time points: every 8 weeks during the first 6 months of PQR309 treatment, subsequently every 2 months up to 2 years and every 6 months afterwards.

Secondary Outcome(s)

Secondary end point(s): Safety parameters:
• Incidence and severity of AEs including SAEs
• Changes in vital signs (pulse rate, blood pressure, body temperature, ECOG performance status, physical examination, body weight and ECG)
• Changes of routine laboratory assessments (haematology, blood chemistry, urinalysis).

Additional Clinical Efficacy:
• Time to Response (TTR), defined as the time from the date of enrollment to the first documentation of response (complete or partial)
• Duration of response (DOR) defined as the time from the date of the first confirmed response to the first documentation of relapse or progressive disease, whichever occurs first
• Time to disease progression (TTP) defined as the time from the date of the first dose of study treatment to the first documentation of progressive disease or death as a result of lymphoma.

Pharmacokinetics:
•PQR309 plasma concentration and PK parameters: Cmax, tmax, AUC0-24, AUClast, AUC0–8, t1/2 and RAC.

Timepoint(s) of evaluation of this end point: Safety parameters:
AEs and SAEs: continuous monitoring from Day 1 to 30 days after last dose.
Vital signs and physical examination: all visits.
Physical examination and ECOG: all visits except Day 2.
Haematology and blood chemistry: all visits except Day 2.
ECG and urinalysis: Screening, Day 1, Day 22, Day 50 , end of treatment.

Pharmacokinetics:
PK Sampling Run In: Day 1, Day 2, Day 8, Day 15, Day 22 and Day 50.
PK Sampling Step 1+2: Day 1, Day 15, Day 22 and Day 50.

Secondary ID(s)

PQR309-002

Source(s) of Monetary Support

PIQUR Therapeutics AG