Phase 2 Study With PQR309 in Relapsed or Refractory Lymphoma Patients

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03127020
• Date of registration: 14/04/2016
• Prospective Registration: Yes
• Primary sponsor: PIQUR Therapeutics AG
• Public title: Phase 2 Study With PQR309 in Relapsed or Refractory Lymphoma Patients
• 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: June 2016
• Target sample size: 9
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03127020
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Germany, Switzerland

Contacts

• Name: Martin Dreyling
• Affiliation: Klinik Universität München

Key inclusion & exclusion criteria

Inclusion Criteria

1. Histologically confirmed diagnosis* of relapsed or refractory lymphoma, received at
least two prior lines of therapy regardless of transformation status. Patients with
relapsed chronic lymphoid leukemia (CLL) are eligible if they have received one or
more prior lines of any approved 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 with > 1.5 cm in longest transverse
diameter.

3. Age = 18 years

4. Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-1 (See Appendix 2).

5. Adequate organ system functions defined as:

1. Absolute neutrophil count (ANC) =1.0x109/l

2. Platelets = 75x109/l

3. Haemoglobin = 85g/L

4. 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

5. Adequate renal function, defined as serum creatinine = 1.5 times ULN

6. Fasting glucose < 7.0 mmol/L

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 consent1.5 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:

1. Absolute neutrophil count (ANC) >1.0x109/l

2. Platelets > 75x109/l

Exclusion Criteria:

Any of the following conditions precludes enrollment of a patient:

1. Immunosuppression due to:

- Allogeneic hematopoietic stem cell transplant (HSCT)

- Any immune-suppressive therapy within 4 weeks prior to trial treatment start

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 and
steroids (steroids as maintenance for adrenal insufficiency are allowed)).

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 (section 11.1.3.7).

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 4 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 (e.g. chronic active hepatitis) 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 levels in inclusion criteria).



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Lymphoma

Non-Hodgkin Lymphoma

Intervention(s)

Drug: PQR309

Primary Outcome(s)

Assessment of Change of Tumor Response Criteria in lymphoma patients During Treatment with PQR309 in patients with relapsed or refractory lymphoma according to Cheston Criteria (5) [Time Frame: 28 days prior to first treatment (baseline), during study treatment every 8 weeks during first 6 months and every 6 months afterwards up to 48 months]

Secondary Outcome(s)

Change in bodyweight/kg [Time Frame: Before treatment on Day 1,2 and after treatment started on Day 1,2, 8, 15, 22, 36, 50 and subsequently every 4 weeks , at the end of treatment and 30 days after last treatment]

Change in pulse rate [Time Frame: Before treatment on Day 1,2 and after treatment started on Day 1,2, 8, 15, 22, 36, 50 and subsequently every 4 weeks , at the end of treatment and 30 days after last treatment]

Change in AUC0-8, [Time Frame: During treatment on Day1, 2, 8, 15,22 and 50]

Change in blood chemistry [Time Frame: Before treatment on Day 1and after treatment started on Day 1, 22, 50 and subsequently every 4 weeks and at the end of treatment]

Change in ECOG (Eastern Cooperative Oncology Group) Performance Status [Time Frame: Before treatment on Day 1,2 and after treatment started on Day 1,8, 15, 22, 36, 50 and subsequently every 4 weeks , at the end of treatment and 30 days after last treatment]

Change in AUC0-24 • [Time Frame: During treatment on Day1, 2, 8, 15,22 and 50]

Change in blood pressure [Time Frame: Before treatment on Day 1,2 and after treatment started on Day 1,2, 8, 15, 22, 36, 50 and subsequently every 4 weeks , at the end of treatment and 30 days after last treatment]

Change in tmax [Time Frame: During treatment on Day1, 2, 8, 15,22 and 50]

Change in haemostasis [Time Frame: Before treatment on Day 1and after treatment started on Day 1, 22, 50 and subsequently every 4 weeks and at the end of treatment]

Change in t1/2 • [Time Frame: During treatment on Day1, 2, 8, 15,22 and 50]

Change in urine analysis [Time Frame: Before treatment on Day 1and after treatment started on Day 1, 22, 50 and subsequently every 4 weeks and at the end of treatment]

Incidence of serious adverse events (SAEs), incidence and severity of all adverse events (AEs) [Time Frame: During treatment on Day 1, 2, 8, 15, 22, 36 and 50; at the endof treatment and 30 days after last dose.]

Change in AUClast, [Time Frame: During treatment on Day1, 2, 8, 15,22 and 50]

Change in body temperature [Time Frame: Before treatment on Day 1,2 and after treatment started on Day 1, 8, 15, 22, 36, 50 and subsequently every 4 weeks , at the end of treatment and 30 days after last treatment]

Change in Cmax [Time Frame: During treatment on Day1, 2,8, 15,22 and 50]

Change in ECG (electrocardiogram) [Time Frame: Before treatment on Day 1and after treatment started on Day 1, 22, 50 and subsequently every 4 weeks and at the end of treatment]

Change in haematology [Time Frame: Before treatment on Day 1,2 and after treatment started on Day 1, 8, 15, 22, 36, 50 and subsequently every 4 weeks , at the end of treatment and 30 days after last treatment]

Change in RAC • [Time Frame: During treatment on Day1, 2, 8, 15,22 and 50]

Change in HbA1c [Time Frame: Before treatment on Day 1and after treatment started on Day 1, 22, 50 and subsequently every 4 weeks and at the end of treatment]

Secondary ID(s)

PQR309-002A

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

University Hospital Munich

Charite University, Berlin, Germany

University Hospital Freiburg

University Hospital, Basel, Switzerland

University of Stuttgart