Non Hodgkin Lymphoma
Conditions
Keywords
Non-Hodgkin lymphoma,, Tenalisib, RP6530
Brief summary
To assess the anti-tumor activity and safety of Tenalisib in patients with relapsed/refractory indolent Non-Hodgkin's Lymphoma (iNHL),
Interventions
DRUGTenalisib,
BID, Orally
Sponsors
Rhizen Pharmaceuticals SA
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients with histologically confirmed diagnosis of indolent B-cell NHL, with histological subtype limited to: 1. Follicular lymphoma (FL) G1, G2, or G3a 2. Marginal zone lymphoma (MZL) (splenic, nodal, or extra-nodal) 3. Lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (LPL/WM) 4. Small lymphocytic lymphoma (SLL) with absolute lymphocyte count \<5 x10\^9/L at the time of diagnosis and at study entry. 2. Relapsed or refractory after ≥ 2 prior lines of therapy (refractory defined as not responding to a standard regimen or progressing within 6 months of the last course of a standard regimen). Patients must have received rituximab and alkylating agents. 3. Patients must have at least one bi-dimensionally measurable lesion (that has not been previously irradiated) with the longest diameter ≥ 1.5 cm. 4. Male or female patients \> 18 years of age. 5. ECOG performance status ≤ 2. 6. Life expectancy of at least 3 months. 7. Adequate bone marrow, liver, and renal function as assessed by the following laboratory requirements conducted within 7 days before starting study treatment: 1. Hemoglobin ≥ 9 g/dl 2. Absolute neutrophil count (ANC) ≥ 1 x 10\^9/L 3. Platelets ≥50 x 10\^9/L (patient without BM involvement) and 30 x 10\^9/L (patient with BM involvement) 4. Total bilirubin ≤1.5 times the upper limit of normal (ULN) 5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x ULN if known liver involvement 6. Creatinine ≤ 1.5 mg/dL OR calculated creatinine clearance ≥ 50 mL/min (as calculated by the Cockcroft-Gault method) 8. Use of an effective means of contraception for female patients of child-bearing potential, and all male partners. 9. Willingness and ability to comply with trial and follow-up procedures, give written informed consent.
Exclusion criteria
1. FL grade 3b or transformed disease or CLL 2. Cancer therapy within 3 weeks (21 days) or 5 half-lives (whichever is shorter) prior to C1D1. Corticosteroids (prednisone or equivalent) at a dose of \< 20 mg daily are allowed. Corticosteroid should be stabilized for at least 1 week prior to C1D1 3. Auto-SCT within 3 months from C1D1 (patients must not have active graft versus- host disease) 4. History of having received an Allo-SCT 5. Active hepatitis B or C infection 6. Known history of human immunodeficiency virus (HIV) infection 7. Evidence of ongoing severe systemic bacterial, fungal or viral infection 8. Known primary central nervous system lymphoma or any preexisting neurologic manifestations 9. Known history of drug-induced liver injury, alcoholic liver disease, primary biliary cirrhosis, ongoing extrahepatic obstruction caused by stones, cirrhosis of the liver or portal hypertension; 10. Prior exposure to drug that specifically inhibits PI3K 11. Pregnancy or lactation 12. Myeloid growth factors or red blood cells/ platelet transfusion within 14 days prior to C1D1 13. Drug administration within 1 week prior to C1D1 1. Strong inhibitors or inducers of CYP3A4, CYP2C9, including grapefruit products, herbal supplements and drugs 2. Substrates of CYP3A4 enzyme with a narrow therapeutic range
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | 7 months | ORR is defined as sum of CR and PR rates and will be assessed according to the Lugano Classification for initial evaluation, staging, and response assessment of Non-Hodgkin lymphoma. (Cheson-2014) |
| Complete Response Rate | 7 months | CR rate will be assessed according to the Lugano Classification for initial evaluation, staging, and response assessment of non-Hodgkin lymphoma. |
| Progression Free Survival (PFS) | From date of first dose of tenalisib until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 7 months | PFS is defined as the time of the first dose of Tenalisib to disease progression or death. |
| Duration of Response (DoR) | 7 months | DoR is measured from the initial response to disease progression or death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events as Assessed by CTCAE v4.0 | 8 months | Safety and tolerability of Tenalisib |
Countries
Australia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tenalisib Participants receive Tenalisib 800 mg BID in 28-Days Cycle for 8 Cycles
Tenalisib,: BID, Orally | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Tenalisib |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 11 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Age, Continuous | 66.575 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 20 Participants |
| Region of Enrollment Australia | 9 participants |
| Region of Enrollment United States | 11 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 13 / 20 |
| serious Total, serious adverse events | 3 / 20 |
Outcome results
Primary
Complete Response Rate
CR rate will be assessed according to the Lugano Classification for initial evaluation, staging, and response assessment of non-Hodgkin lymphoma.
Time frame: 7 months
Population: Patients who received at least 1 dose of study medication and provided at least 1 post-baseline efficacy assessment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenalisib | Complete Response Rate | 0.00 Percent of participants |
Primary
Duration of Response (DoR)
DoR is measured from the initial response to disease progression or death
Time frame: 7 months
Population: Patients who received at least 1 dose of study medication and provide at least 1 post-baseline efficacy assessment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenalisib | Duration of Response (DoR) | 0 days |
Primary
Objective Response Rate (ORR)
ORR is defined as sum of CR and PR rates and will be assessed according to the Lugano Classification for initial evaluation, staging, and response assessment of Non-Hodgkin lymphoma. (Cheson-2014)
Time frame: 7 months
Population: Patients who received at least 1 dose of study medication and provided at least 1 post-baseline efficacy assessment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenalisib | Objective Response Rate (ORR) | 5.3 Percent of participants |
Primary
Progression Free Survival (PFS)
PFS is defined as the time of the first dose of Tenalisib to disease progression or death.
Time frame: From date of first dose of tenalisib until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 7 months
Population: Patients who received at least 1 dose of study medication and provide at least 1 post-baseline efficacy assessment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tenalisib | Progression Free Survival (PFS) | 113 days |
Secondary
Number of Participants With Treatment-emergent Adverse Events as Assessed by CTCAE v4.0
Safety and tolerability of Tenalisib
Time frame: 8 months
Population: Patients who received at least 1 dose of study medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenalisib | Number of Participants With Treatment-emergent Adverse Events as Assessed by CTCAE v4.0 | 18 participants |