A Phase I/Ib, Dose Escalation Study to Evaluate Safety and Efficacy of RP6530, a dual PI3K delta/gamma inhibitor, in Patients with Relapsed or Refractory T-cell Lymphoma
The goal of this clinical research study is to find the highest tolerable dose of RP6530 that can be given to patients with cutaneous T-cell lymphoma (CTCL). Another goal of this study is to learn if RP6530 can help to control CTCL. The safety of the drug will also be studied.
Disease Group: Lymphoma,Skin
Treatment Agent: RP6530
Treatment Location: Both at MDACC & and Other Sites
Sponsor: Rhizen Pharmaceuticals SA
Primary Objective To evaluate the safety and the maximum tolerated dose (MTD) of RP6530 in patients with relapsed/refractory T-cell lymphoma (CTCL/PTCL). To evaluate the pharmacokinetic (PK) effects of RP6530. Secondary Objectives To examine the pharmacodynamic (PD) effects of RP6530. To assess and the overall response rate (ORR) and duration of response (DoR) in patients with relapsed/refractory T-cell lymphoma. Exploratory Objectives Correlation of treatment outcomes with biomarkers which include but are not limited to quantitative and qualitative measurements of cytokines, chemokines and aberrations indicative of PI3K function and RP6530 efficacy.
IRB Review and Approval Date: 09/24/2015
Recruitment Status: Open
Projected Accrual: 58
1) Histologically confirmed T cell Non-Hodgkin Lymphoma (T-NHL) as
approved by the Medical Monitor or PI/Co-PI.
2) Disease status defined as: --Refractory to or relapsed after > or = 1 prior treatment lines. --Patients who are not eligible for transplantation or any standard and/or approved therapy known to be life prolonging or life saving (patients who may be eligible for transplantation or any standard and/or approved therapy but have declined therapy, or in the investigators opinion based on the patient’s condition, an investigational therapy may benefit more than existing approved therapies are eligible for the study).
3) Patients with a measurable or evaluable disease. --In case of radiologically measurable lesions, the longest diameter should be > or = 2cm in PTCL patients. --PTCL patients with non-measurable lesions but assessable disease (e.g. marrow disease without other radiographically measurable disease) can be enrolled in dose-escalation phase as approved by PI/Co-PI.
4) Adequate organ system function, defined as follows: --Patients with haemoglobin levels and/or neutrophil and platelet counts under these values will be eligible in the case abnormalities are due to tumor dissemination or infiltration and according to physician's discretion and under his direct responsibility. (a) Hemoglobin > or = 8 g/dL, (b) Absolute neutrophil count (ANC) > or = 0.75 x 10^9/L (c)Platelets > or = 50 x 10^9/L --Total bilirubin < or =1.5 times the upper limit of normal (ULN) --Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < or = 2.5 x ULN if no liver involvement or 5 x the ULN if known liver involvement. --Creatinine < or = 2.0 mg/dL OR calculated creatinine clearance > or = 50 mL/min as calculated by the Cockcroft-Gault method
5) ECOG performance status < or = 2.
6) Life expectancy of at least 12 weeks.
7) Patients must be > or = 18 years of age.
8) Ability to swallow and retain oral medication.
9) Female patients who are not of child-bearing potential or female patients of child-bearing potential who have a negative serum pregnancy test within 72 hours prior to initial trial treatment. Female patients of child-bearing potential, and all male partners must consent to use a medically acceptable method of contraception throughout the study period and for 4 weeks plus 5T1/2 (48 hrs) after the last dose of RP6530. A barrier method of contraception must be included.
10) Male patients willing to use adequate contraceptive measures throughout the study period and for 12 weeks plus 5T1/2 (48 hrs) after the last dose of RP6530.
11) Willingness and ability to comply with trial and follow-up procedures.
12) Ability to understand the nature of this trial and give written informed consent.
1) Any cancer therapy (i.e., chemotherapy, radiation therapy,
immunotherapy, biologic therapy, hormonal therapy, surgery and/or tumor
embolization) in the last 3 weeks or the last 5T1/2 of the agent,
whichever is shorter. Limited palliative radiation <2 weeks.
2) Autologous hematologic stem cell transplant within 3 months of study entry. Allogeneic hematologic stem cell transplant within 12 months. Active graft-versus-host disease.
3) Active HBV, HCV or HIV infection.
4) Use of an investigational drug in the last 4 weeks prior to the first dose of RP6530
5) Treatment with GS-1101 (CAL-101, idelalisib), IPI-145, TGR-1202 or any drug that specifically inhibits PI3K/ mTOR (including temsirolimus, everolimus), AKT or BTK Inhibitor (including Ibrutinib) in last 6 months
6) Patient has received wide field radiotherapy (including therapeutic radioisotopes such as Yttrium-90) < or = 28 days or limited field radiation for palliation < or = 14 days prior to starting RP6530 or has not recovered from side effects of such therapy
7) Ongoing immunosuppressive therapy including systemic corticosteroids (prednisone or equivalent </=10 mg daily allowed as clinically warranted). Patients are allowed to use topical or inhaled corticosteroids.
8) Known history of drug-induced liver injury, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, ongoing extrahepatic obstruction caused by stones, cirrhosis of the liver or portal hypertension.
9) Patients with uncontrolled Diabetes Type I or Type II (HbA1c >8% assessed locally).
10) Any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: a) Symptomatic, or history of documented congestive heart failure (New York Heart Association functional classification III-IV b) QTcF > 470 msec c) Angina not well-controlled by medication d) Poorly controlled or clinically significant atherosclerotic vascular disease including cerebrovascular accident (CVA), transient ischemic attack (TIA), angioplasty, cardiac or vascular stenting in the past 6 months e) Active or uncontrolled severe infections requiring IV antibiotics f) Patients with hemophilia or even Von Willebrand’s disease should be excluded.
11) Herbal preparations/medications must be discontinued 7 days prior to first dose of study drug.
12) Presence of other active cancers, or history of treatment for invasive cancer < or =3 years. Patients with stage I cancer who have received definitive local treatment at least 3 years previously, and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e. non-invasive) are eligible, as are patients with history of non-melanoma skin cancer.
13) Women who are pregnant or lactating.
14) Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
15) Concurrent condition that in the investigator’s opinion would jeopardize compliance with the protocol.
16) Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol.
Information and next steps
For general questions about clinical trials: