Efficacy and Safety Study of Tenalisib (RP6530), a Novel PI3K δ/γ Dual Inhibitor in Patients With Relapsed/Refractory Indolent Non-Hodgkin's Lymphoma (iNHL)

• Sponsor: Rhizen Pharmaceuticals SA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03711578
• Collaborator: (none)
• Enrollment: 20
• Locations: 12
• Arm: 1
• Actual Duration (Months): 22.7
• Patients Per Site: 1.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

To assess the anti-tumor activity and safety of Tenalisib in patients with relapsed/refractory indolent Non-Hodgkin's Lymphoma (iNHL),

Condition or Disease	Intervention/Treatment	Phase
Non Hodgkin Lymphoma	Drug: Tenalisib,	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label, Phase II Study to Evaluate the Efficacy and Safety of Tenalisib (RP6530), a Novel PI3K δ/γ Dual Inhibitor in Adult Patients With Relapsed/Refractory Indolent Non-Hodgkin's Lymphoma (iNHL)
• Actual Study Start Date: Nov 25, 2018
• Actual Primary Completion Date: Jun 16, 2020
• Actual Study Completion Date: Oct 16, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tenalisib Participants receive Tenalisib 800 mg BID in 28-Days Cycle for 8 Cycles	Drug: Tenalisib,; BID, Orally; Other Names: RP6530

Outcome Measures

Primary Outcome Measures

1. 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)

2. 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.

3. 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.

4. Duration of Response (DoR) [7 months]

   DoR is measured from the initial response to disease progression or death

Secondary Outcome Measures

1. Number of Participants With Treatment-emergent Adverse Events as Assessed by CTCAE v4.0 [8 months]

   Safety and tolerability of Tenalisib

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients with histologically confirmed diagnosis of indolent B-cell NHL, with histological subtype limited to:

2. Follicular lymphoma (FL) G1, G2, or G3a

3. Marginal zone lymphoma (MZL) (splenic, nodal, or extra-nodal)

4. Lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (LPL/WM)

5. Small lymphocytic lymphoma (SLL) with absolute lymphocyte count <5 x10^9/L at the time of diagnosis and at study entry.

6. 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.

7. Patients must have at least one bi-dimensionally measurable lesion (that has not been previously irradiated) with the longest diameter ≥ 1.5 cm.

8. Male or female patients > 18 years of age.

9. ECOG performance status ≤ 2.

10. Life expectancy of at least 3 months.

11. Adequate bone marrow, liver, and renal function as assessed by the following laboratory requirements conducted within 7 days before starting study treatment:

12. Hemoglobin ≥ 9 g/dl

13. Absolute neutrophil count (ANC) ≥ 1 x 10^9/L

14. Platelets ≥50 x 10^{9/L (patient without BM involvement) and 30 x 10}9/L (patient with BM involvement)

15. Total bilirubin ≤1.5 times the upper limit of normal (ULN)

16. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x ULN if known liver involvement

17. Creatinine ≤ 1.5 mg/dL OR calculated creatinine clearance ≥ 50 mL/min (as calculated by the Cockcroft-Gault method)

18. Use of an effective means of contraception for female patients of child-bearing potential, and all male partners.

19. 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

14. Strong inhibitors or inducers of CYP3A4, CYP2C9, including grapefruit products, herbal supplements and drugs

15. Substrates of CYP3A4 enzyme with a narrow therapeutic range

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clearview Cancer Institute	Huntsville	Alabama	United States	35805
2	Colorado Blood Cancer Institute	Denver	Colorado	United States	80218
3	Florida cancer specialists & Research Institute	Florida City	Florida	United States	33401
4	Florida Cancer Specialist/ South	Fort Myers	Florida	United States	33908
5	Florida Cancer Specialists/North	Saint Petersburg	Florida	United States	33705
6	HCA Midwest Health Kansas City	Kansas City	Missouri	United States	64132
7	Tennessee Oncology	Chattanooga	Tennessee	United States	37404
8	Tennessee Oncology	Nashville	Tennessee	United States	37203
9	Blacktown Hospital, Blacktown Cancer and Haematology Center	Blacktown	New South Wales	Australia	2148
10	Brisbane Clinic for Lymphoma, Myeloma and Leukaemia,	Greenslopes,	Queensland	Australia	4120
11	John Flynn Private Hospital,	Tugun	Queensland	Australia	4224
12	Royal Adelaide Hospital	Adelaide	South Australia	Australia	5000

Sponsors and Collaborators

• Rhizen Pharmaceuticals SA

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Dec 4, 2018
• Statistical Analysis Plan - Aug 7, 2020

More Information

Publications

None provided.

• Responsible Party: Rhizen Pharmaceuticals SA
• ClinicalTrials.gov Identifier: NCT03711578
• Other Study ID Numbers: RP6530-1802
• First Posted: Oct 18, 2018
• Last Update Posted: Aug 12, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Rhizen Pharmaceuticals SA: Non-Hodgkin lymphoma,; Tenalisib; RP6530
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Tenalisib

Study Results

Participant Flow

Arm/Group Title	Tenalisib
Arm/Group Description	Participants receive Tenalisib 800 mg BID in 28-Days Cycle for 8 Cycles Tenalisib,: BID, Orally
Period Title: Overall Study
STARTED	20
COMPLETED	20
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Tenalisib
Arm/Group Description	Participants receive Tenalisib 800 mg BID in 28-Days Cycle for 8 Cycles Tenalisib,: BID, Orally
Overall Participants	20
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	9 45%
>=65 years	11 55%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	66.575
Sex: Female, Male (Count of Participants)
Female	7 35%
Male	13 65%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	20 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	11 55%
Australia	9 45%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR)
Description	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

Outcome Measure Data

Analysis Population Description

Patients who received at least 1 dose of study medication and provided at least 1 post-baseline efficacy assessment

Arm/Group Title	Tenalisib
Arm/Group Description	Participants receive Tenalisib 800 mg BID in 28-Days Cycle for 8 Cycles Tenalisib,: BID, Orally
Measure Participants	19
Number (95% Confidence Interval) [Percent of participants]	5.3 26.5%

2. Primary Outcome

Title	Complete Response Rate
Description	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

Outcome Measure Data

Analysis Population Description

Patients who received at least 1 dose of study medication and provided at least 1 post-baseline efficacy assessment

Arm/Group Title	Tenalisib
Arm/Group Description	Participants receive Tenalisib 800 mg BID in 28-Days Cycle for 8 Cycles Tenalisib,: BID, Orally
Measure Participants	19
Number (95% Confidence Interval) [Percent of participants]	0.00 0%

3. Primary Outcome

Title	Progression Free Survival (PFS)
Description	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

Outcome Measure Data

Analysis Population Description

Patients who received at least 1 dose of study medication and provide at least 1 post-baseline efficacy assessment

Arm/Group Title	Tenalisib
Arm/Group Description	Participants receive Tenalisib 800 mg BID in 28-Days Cycle for 8 Cycles Tenalisib,: BID, Orally
Measure Participants	19
Median (95% Confidence Interval) [days]	113

4. Primary Outcome

Title	Duration of Response (DoR)
Description	DoR is measured from the initial response to disease progression or death
Time Frame	7 months

Outcome Measure Data

Analysis Population Description

Patients who received at least 1 dose of study medication and provide at least 1 post-baseline efficacy assessment

Arm/Group Title	Tenalisib
Arm/Group Description	Participants receive Tenalisib 800 mg BID in 28-Days Cycle for 8 Cycles Tenalisib,: BID, Orally
Measure Participants	19
Number [days]	0

5. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events as Assessed by CTCAE v4.0
Description	Safety and tolerability of Tenalisib
Time Frame	8 months

Outcome Measure Data

Analysis Population Description

Patients who received at least 1 dose of study medication

Arm/Group Title	Tenalisib
Arm/Group Description	Participants receive Tenalisib 800 mg BID in 28-Days Cycle for 8 Cycles Tenalisib,: BID, Orally
Measure Participants	20
Number [participants]	18 90%

Adverse Events

Time Frame	8 months
Adverse Event Reporting Description	Summary of Treatment-Emergent Adverse Events-(Causality All). Patients were monitored for adverse events and both related and as well as non-related adverse events were captured during the study. All adverse events (irrespective of causality) are reported here.
Arm/Group Title	Tenalisib
Arm/Group Description	Participants receive Tenalisib 800 mg BID in 28-Days Cycle for 8 Cycles Tenalisib,: BID, Orally
All Cause Mortality
	Tenalisib
	Affected / at Risk (%)	# Events
Total	0/20 (0%)
Serious Adverse Events
	Tenalisib
	Affected / at Risk (%)	# Events
Total	3/20 (15%)
General disorders
Pyrexia	1/20 (5%)	1
Metabolism and nutrition disorders
Hypercalcemia	1/20 (5%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic carcinoma	1/20 (5%)	1
Other (Not Including Serious) Adverse Events
	Tenalisib
	Affected / at Risk (%)	# Events
Total	13/20 (65%)
Blood and lymphatic system disorders
Thrombocytopenia	1/20 (5%)	2
Anemia	2/20 (10%)	3
Neutropenia	1/20 (5%)	1
Cardiac disorders
Palpitations	1/20 (5%)	1
Ear and labyrinth disorders
Tinnitus	1/20 (5%)	1
Gastrointestinal disorders
Diarrhoea	4/20 (20%)	4
Nausea	3/20 (15%)	3
Abdominal pain	2/20 (10%)	2
Vomiting	2/20 (10%)	2
Constipation	2/20 (10%)	2
Abdominal discomfort	1/20 (5%)	1
Abdominal distension	1/20 (5%)	1
Abdominal pain upper	1/20 (5%)	1
Eructation	1/20 (5%)	1
General disorders
Fatigue	5/20 (25%)	5
Chills	1/20 (5%)	2
Pyrexia	2/20 (10%)	2
Influenza like illness	1/20 (5%)	1
Immune system disorders
Allergy to arthropod bite	1/20 (5%)	1
Infections and infestations
Upper respiratory tract infection	2/20 (10%)	2
Escherichia urinary tract infection	1/20 (5%)	1
Fungal infection	1/20 (5%)	1
Influenza	1/20 (5%)	1
Lower respiratory tract infection	1/20 (5%)	1
Oral candidiasis	1/20 (5%)	1
Serratia infection	1/20 (5%)	1
Viral infection	1/20 (5%)	1
Injury, poisoning and procedural complications
Fall	1/20 (5%)	1
Investigations
Gamma-glutamyltransferase increased	2/20 (10%)	2
Neutrophil Count Decreased	2/20 (10%)	3
Alanine aminotransferase increased	1/20 (5%)	3
Activated partial thromboplastin time prolonged	1/20 (5%)	2
Platelet count decreased	1/20 (5%)	3
Metabolism and nutrition disorders
Decreased appetite	3/20 (15%)	3
Hypophosphataemia	1/20 (5%)	1
Hyperuricaemia	1/20 (5%)	1
Hyperglycemia	2/20 (10%)	2
Musculoskeletal and connective tissue disorders
Muscle spasms	4/20 (20%)	5
Arthralgia	2/20 (10%)	2
Bone pain	1/20 (5%)	1
Muscular weakness	1/20 (5%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	1/20 (5%)	1
Malignant melanoma	1/20 (5%)	1
Nervous system disorders
Dysgeusia	2/20 (10%)	2
Dizziness	1/20 (5%)	1
Headache	1/20 (5%)	1
Neuropathy peripheral	1/20 (5%)	1
Neurological symptoms	1/20 (5%)	1
Psychiatric disorders
Insomnia	1/20 (5%)	1
Renal and urinary disorders
Dysuria	1/20 (5%)	1
Haematuria	1/20 (5%)	1
Nocturia	1/20 (5%)	1
Urinary retention	1/20 (5%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/20 (5%)	1
Dyspnoea	1/20 (5%)	1
Epistaxis	1/20 (5%)	1
Nasal congestion	1/20 (5%)	1
Nasal discomfort	1/20 (5%)	1
Productive cough	1/20 (5%)	1
Tachypnoea	1/20 (5%)	1
Upper-airway cough syndrome	1/20 (5%)	1
Wheezing	1/20 (5%)	1
Skin and subcutaneous tissue disorders
Pruritis	2/20 (10%)	2
Rash maculo-papular	1/20 (5%)	1
Hyperhidrosis	1/20 (5%)	1
Rash	1/20 (5%)	1
Rash generalized	1/20 (5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.