Phase 2 Study With PQR309 in Relapsed or Refractory Lymphoma Patients

NCT03127020 | Completed Phase 2

• 1 other identifier: PQR309-002A
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

The main goal of this study is to determine the Maximum Tolerated Dose (MTD) and the Recommended Phase II Dose (RP2D) as well as preliminary antitumor activity of PQR309 administered orally, as once daily capsules continuously and on intermittent schedule, in patients with relapsed or refractory lymphomas.

Conditions

Lymphoma; Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• 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)

  Radiological lymphoma Evaluation (CT or other indicated according to institutional Standard practice), clinical examination and bone marrow biopsy

  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 Outcomes (19)

• Incidence of serious adverse events (SAEs), incidence and severity of all adverse events (AEs)

  During treatment on Day 1, 2, 8, 15, 22, 36 and 50; at the endof treatment and 30 days after last dose.

• Change in pulse rate

  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 blood pressure

  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 body temperature

  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 ECOG (Eastern Cooperative Oncology Group) Performance Status

  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

Other Outcomes (1)

• Change in insulin/ c-Peptide/ glucose

  During treatment on Day 1, 2, 8,15,22 and 50

Study Arms (1)

PQR309

EXPERIMENTAL

PQR309 being taken continuously on daily basis (60,80mg) or intermittent (120mg, 140mg, 160mg) dosing

Drug: PQR309

Interventions

PQR309 DRUG

taken continuously on daily basis (60mg, 80mg) or intermittent dosing (120mg, 140mg, 160mg)

Also known as: PI3K Inhibitor (phosphatidylinositol 3-kinase)

PQR309

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-1 (See Appendix 2).
• Adequate organ system functions defined as:
• Absolute neutrophil count (ANC) ≥1.0x109/l
• Platelets ≥ 75x109/l
• Haemoglobin ≥ 85g/L
• 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
• Adequate renal function, defined as serum creatinine ≤ 1.5 times ULN
• Fasting glucose \< 7.0 mmol/L
• Ability and willingness to swallow and retain oral medication.
• Willingness and ability to comply with the trial procedures
• Female and male patients with reproductive potential must agree to use effective contraception from screening until 90 days after discontinuation of PQR309
• Signed informed consent1.5 cm in longest transverse diameter.

You may not qualify if:

• Any of the following conditions precludes enrollment of a patient:
• Immunosuppression due to:
• Allogeneic hematopoietic stem cell transplant (HSCT)
• Any immune-suppressive therapy within 4 weeks prior to trial treatment start
• Autologous stem cell transplant within 3 months prior to trial treatment start.
• 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)).
• 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).
• Use of any investigational drug within 21 days prior to trial treatment start.
• Patients who experienced National Cancer Institute (NCI) Common Terminology Criteria For Adverse Events (CTCAE) grade 4 on PI3K/mTOR inhibitors
• Any major surgery, chemotherapy or immunotherapy within 21 days prior to trial treatment start.
• Symptomatic or progressing central nervous system (CNS) involvement. Exception: Patients with meningeal involvement can be included upon discussion between the sponsor and the investigator.
• Persisting toxicities NCI CTCAE ≥2 related to prior anticancer therapy
• Presence of gastrointestinal disease or any other condition that could interfere significantly with the absorption of the study drug.
• 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
• 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.

Sponsors & Collaborators

• PIQUR Therapeutics AG: lead
• University Hospital, Basel, Switzerland: collaborator
• University Hospital Munich: collaborator
• University Hospital Freiburg: collaborator
• Charite University, Berlin, Germany: collaborator
• University of Stuttgart: collaborator

Study Sites (1)

Medizinische Klinik und Poliklinik III

Munich, Bavaria, 81377, Germany

Location

MeSH Terms

Conditions

Lymphoma; Lymphoma, Non-Hodgkin

Interventions

Phosphatidylinositol 3-Kinase

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphatidylinositol 3-Kinases; Phosphotransferases (Alcohol Group Acceptor); Phosphotransferases; Transferases; Enzymes; Enzymes and Coenzymes; Intracellular Signaling Peptides and Proteins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Martin Dreyling

  Klinik Universität München

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2016
• First Posted: April 25, 2017
• Study Start: June 1, 2016
• Primary Completion: March 21, 2019
• Last Updated: June 28, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)