Safety and Efficacy Study of a Dual PI3K Delta/Gamma Inhibitor in T-cell Lymphoma

• Sponsor: Rhizen Pharmaceuticals SA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02567656
• Collaborator: (none)
• Enrollment: 58
• Locations: 8
• Arm: 1
• Duration (Months): 39.3
• Patients Per Site: 7.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety, PK and efficacy of RP6530, a dual PI3K delta/gamma inhibitor in patients with relapsed and refractory T-cell Lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell, Cutaneous	Drug: RP6530	Phase 1

Detailed Description

Safety: Treatment-Emergent AE; Treatment-Related AE, SAE and Clinical significant AE; Dose Limiting Toxicities (DLT). PK: Peak Plasma Concentration (Cmax), Area under the plasma concentration versus time curve (AUC), Time of Maximum concentration observed (Tmax). Efficacy: Overall Response Rate (ORR), Progression Free Survival (PFS), Overall Survival (OS) and Duration of Response.

Study Design

• Study Type: Interventional
• Actual Enrollment: 58 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/Ib, Dose Escalation Study to Evaluate Safety and Efficacy of RP6530, a Dual PI3K δ/γ Inhibitor, in Patients With Relapsed or Refractory T-cell Lymphoma
• Study Start Date: Sep 1, 2015
• Actual Primary Completion Date: Mar 1, 2018
• Actual Study Completion Date: Dec 10, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single arm RP6530 administered orally twice a day.	Drug: RP6530; Tablet starting at 200 mg; Other Names: PI3K inhibitor

Outcome Measures

Primary Outcome Measures

1. Safety of RP6530 [28 days]

   Number of participants with Treatment-Related Adverse Events as Assessed by CTACE v4.0

Secondary Outcome Measures

1. Overall Response Rate (ORR) With RP6530 [8 months]

   ORR is defined as sum of CR and PR rates, Response assessment for PTCL based on IWG criteria (Cheson 2007) and CTCL on mSWAT/Global assessment (ISCL/EORTC guideline).

2. Duration of Response (DOR) With RP6530 [24 months]

   The time period from the response achieved in patient until the disease progression.

3. Peak Plasma Concentration (Cmax) [Day 1 of Cycle 1]

   Peak Plasma Concentration (Cmax) of RP6530

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically confirmed T cell Non-Hodgkin Lymphoma (T-NHL)

• Refractory to or relapsed after at least 1 prior treatment line.

• ECOG performance status ≤2

• Patients must be ≥18 years of age

• Able to give a written informed consent.

Exclusion Criteria:

• Any cancer therapy in the last 3 weeks or limited palliative radiation <2 weeks

• Patients with HBV, HCV or HIV infection

• Previous therapy with GS-1101 (CAL-101, Idelalisib), IPI-145 (Duvelisib), TGR-1202 or any drug that specifically inhibits PI3K/ mTOR (including temsirolimus, everolimus), AKT or BTK Inhibitor (including Ibrutinib) in last 6 months

• Patients on immunosuppressive therapy including systemic corticosteroids.

• Patients with known history of liver disorders.

• Patients with uncontrolled Diabetes Type I or Type II

• Any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study.

• Women who are pregnant or lactating.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope	Duarte	California	United States	91010
2	Chao Family Comprehensive Cancer Center University of California Irvine	Orange	California	United States	92868
3	University of Colorado Cancer Center	Aurora	Colorado	United States	80045
4	Emory University School of Medicine	Atlanta	Georgia	United States	30322
5	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0944
6	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
7	University Hospitals Cleveland Medical Center	Cleveland	Ohio	United States	44106-5028
8	MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• Rhizen Pharmaceuticals SA

Investigators

• Principal Investigator: Auris Huen, MD, MD Anderson Cancer Center, Houston, Tx.

Study Documents (Full-Text)

• Study Protocol - May 23, 2018
• Statistical Analysis Plan - May 23, 2018

More Information

Publications

None provided.

• Responsible Party: Rhizen Pharmaceuticals SA
• ClinicalTrials.gov Identifier: NCT02567656
• Other Study ID Numbers: RP6530-1401; 124584
• First Posted: Oct 5, 2015
• Last Update Posted: Jan 13, 2020
• Last Verified: Dec 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Rhizen Pharmaceuticals SA: CTCL; PTCL; RP6530
• Additional relevant MeSH terms: Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell, Cutaneous; Tenalisib

Study Results

Participant Flow

Arm/Group Title	Dose escalation_Cohort 1_200 mg	Dose escalation_Cohort 2_400 mg	Dose escalation_Cohort 3_800 mg (Fasting)	Dose escalation_Cohort 4_800 mg (Fed)	Dose expansion_PTCL_800 mg (Fasting)	Dose expansion_CTCL_800 mg (Fasting)
Arm/Group Description	RP6530 administered 200 mg orally twice a day.	RP6530 administered 400 mg orally twice a day.	RP6530 administered 800 mg orally twice a day under fasting condition	RP6530 administered 800 mg orally twice a day under fed condition	RP6530 administered 800 mg orally twice a day under fasting condition	RP6530 administered 800 mg orally twice a day under fasting condition
Period Title: Overall Study
STARTED	4	4	5	6	19	20
COMPLETED	3	3	3	6	19	20
NOT COMPLETED	1	1	2	0	0	0

Baseline Characteristics

Arm/Group Title	Dose escalation_Cohort 1_200 mg	Dose escalation_Cohort 2_400 mg	Dose escalation_Cohort 3_800 mg (Fasting)	Dose escalation_Cohort 4_800 mg (Fed)	Dose expansion_PTCL_800 mg (Fasting)	Dose expansion_CTCL_800 mg (Fasting)	Total
Arm/Group Description	RP6530 administered 200 mg orally twice a day.	RP6530 administered 400 mg orally twice a day.	RP6530 administered 800 mg orally twice a day under fasting condition	RP6530 administered 800 mg orally twice a day under fed condition	RP6530 administered 800 mg orally twice a day under fasting condition	RP6530 administered 800 mg orally twice a day under fasting condition	Total of all reporting groups
Overall Participants	4	4	5	6	19	20	58
Age (Years) [Median (Full Range) ]
Median (Full Range) [Years]	63.45	65.03	67.89	65.86	63.95	67.07	67.07
Sex: Female, Male (Count of Participants)
Female	3 75%	2 50%	2 40%	1 16.7%	7 36.8%	13 65%	28 48.3%
Male	1 25%	2 50%	3 60%	5 83.3%	12 63.2%	7 35%	30 51.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	1 5.3%	0 0%	1 1.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	4 21.1%	4 20%	8 13.8%
White	4 100%	4 100%	5 100%	6 100%	14 73.7%	16 80%	49 84.5%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	4 100%	4 100%	5 100%	6 100%	19 100%	20 100%	58 100%

Outcome Measures

1. Primary Outcome

Title	Safety of RP6530
Description	Number of participants with Treatment-Related Adverse Events as Assessed by CTACE v4.0
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

DLT assessment performed in patients who participated in dose escalation phase; A toxicity will be considered dose-limiting if it occurs during the first cycle (4-weeks) treatment with Tenalisib and is considered related to Tenalisib.

Arm/Group Title	Dose escalation_Cohort 1_200 mg	Dose escalation_Cohort 2_400 mg	Dose escalation_Cohort 3_800 mg (Fasting)	Dose escalation_Cohort 4_800 mg (Fed)	Dose expansion_PTCL_800 mg (Fasting)	Dose expansion_CTCL_800 mg (Fasting)
Arm/Group Description	RP6530 administered 200 mg orally twice a day.	RP6530 administered 400 mg orally twice a day.	RP6530 administered 800 mg orally twice a day under fasting condition	RP6530 administered 800 mg orally twice a day under fed condition	RP6530 administered 800 mg orally twice a day under fasting condition	RP6530 administered 800 mg orally twice a day under fasting condition
Measure Participants	4	4	5	6	0	0
No.of Participants with Dose Limiting Toxicities	0 0%	0 0%	0 0%	2 33.3%	0 0%	0 0%
No.of Participants without Dose Limiting Toxicitie	4 100%	4 100%	5 100%	4 66.7%	0 0%	0 0%

2. Secondary Outcome

Title	Overall Response Rate (ORR) With RP6530
Description	ORR is defined as sum of CR and PR rates, Response assessment for PTCL based on IWG criteria (Cheson 2007) and CTCL on mSWAT/Global assessment (ISCL/EORTC guideline).
Time Frame	8 months

Outcome Measure Data

Analysis Population Description

Patients were considered for efficacy analysis as per protocol only if they had one post treatment efficacy assessment at C3D1

Arm/Group Title	Dose escalation_Cohort 1_200 mg	Dose escalation_Cohort 2_400 mg	Dose escalation_Cohort 3_800 mg (Fasting)	Dose escalation_Cohort 4_800 mg (Fed)	Dose expansion_PTCL_800 mg (Fasting)	Dose expansion_CTCL_800 mg (Fasting)
Arm/Group Description	RP6530 administered 200 mg orally twice a day.	RP6530 administered 400 mg orally twice a day.	RP6530 administered 800 mg orally twice a day under fasting condition	RP6530 administered 800 mg orally twice a day under fed condition	RP6530 administered 800 mg orally twice a day under fasting condition	RP6530 administered 800 mg orally twice a day under fasting condition
Measure Participants	3	2	3	5	10	12
Count of Participants [Participants]	1 25%	2 50%	2 40%	2 33.3%	4 21.1%	5 25%

3. Secondary Outcome

Title	Duration of Response (DOR) With RP6530
Description	The time period from the response achieved in patient until the disease progression.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

Duration of Response (DoR) is defined as the time when the measurement criteria are first met for PR or CR (whichever is reported first) until the date of documented disease progression or death. Overall number of Participants analyzed for DoR will be the participants who met response as CR or PR

Arm/Group Title	Dose escalation_Cohort 1_200 mg	Dose escalation_Cohort 2_400 mg	Dose escalation_Cohort 3_800 mg (Fasting)	Dose escalation_Cohort 4_800 mg (Fed)	Dose expansion_PTCL_800 mg (Fasting)	Dose expansion_CTCL_800 mg (Fasting)
Arm/Group Description	RP6530 administered 200 mg orally twice a day.	RP6530 administered 400 mg orally twice a day.	RP6530 administered 800 mg orally twice a day under fasting condition	RP6530 administered 800 mg orally twice a day under fed condition	RP6530 administered 800 mg orally twice a day under fasting condition	RP6530 administered 800 mg orally twice a day under fasting condition
Measure Participants	1	2	2	2	4	5
Median (Full Range) [Days]	147	72	313	99	141	307

4. Secondary Outcome

Title	Peak Plasma Concentration (Cmax)
Description	Peak Plasma Concentration (Cmax) of RP6530
Time Frame	Day 1 of Cycle 1

Outcome Measure Data

Analysis Population Description

Peak Plasma Concentration (Cmax) of RP6530 at Cycle 1 day 1

Arm/Group Title	Dose escalation_Cohort 1_200 mg	Dose escalation_Cohort 2_400 mg	Dose escalation_Cohort 3_800 mg (Fasting)	Dose escalation_Cohort 4_800 mg (Fed)
Arm/Group Description	RP6530 administered 200 mg orally twice a day.	RP6530 administered 400 mg orally twice a day.	RP6530 administered 800 mg orally twice a day under fasting condition	RP6530 administered 800 mg orally twice a day under fed condition
Measure Participants	4	4	5	6
Mean (Standard Deviation) [ng/mL]	1297.65 (622.81)	2196.65 (676.45)	3995.68 (1392.74)	2668.05 (1713.17)

Adverse Events

Time Frame	24 months
Adverse Event Reporting Description	Summary of Related Treatment Emergent Adverse Events - All Patients
Arm/Group Title	Dose escalation_Cohort 1_200 mg		Dose escalation_Cohort 2_400 mg		Dose escalation_Cohort 3_800 mg (Fasting)		Dose escalation_Cohort 4_800 mg (Fed)		Dose expansion_PTCL_800 mg (Fasting)		Dose expansion_CTCL_800 mg (Fasting)
Arm/Group Description	RP6530 administered 200 mg orally twice a day.		RP6530 administered 400 mg orally twice a day.		RP6530 administered 800 mg orally twice a day under fasting condition		RP6530 administered 800 mg orally twice a day under fed condition		RP6530 administered 800 mg orally twice a day under fasting condition		RP6530 administered 800 mg orally twice a day under fasting condition
All Cause Mortality
	Dose escalation_Cohort 1_200 mg		Dose escalation_Cohort 2_400 mg		Dose escalation_Cohort 3_800 mg (Fasting)		Dose escalation_Cohort 4_800 mg (Fed)		Dose expansion_PTCL_800 mg (Fasting)		Dose expansion_CTCL_800 mg (Fasting)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		1/4 (25%)		1/5 (20%)		1/6 (16.7%)		3/19 (15.8%)		1/20 (5%)
Serious Adverse Events
	Dose escalation_Cohort 1_200 mg		Dose escalation_Cohort 2_400 mg		Dose escalation_Cohort 3_800 mg (Fasting)		Dose escalation_Cohort 4_800 mg (Fed)		Dose expansion_PTCL_800 mg (Fasting)		Dose expansion_CTCL_800 mg (Fasting)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/4 (0%)		0/5 (0%)		0/6 (0%)		3/19 (15.8%)		3/20 (15%)
Eye disorders
Diplopia	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	0/19 (0%)	0	1/20 (5%)	1
Gastrointestinal disorders
Pyrexia	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	1/19 (5.3%)	1	0/20 (0%)	0
Immune system disorders
Hypersensitivity	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	1/19 (5.3%)	1	0/20 (0%)	0
Infections and infestations
Sepsis syndrome	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	0/19 (0%)	0	1/20 (5%)	1
Skin Infection	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	0/19 (0%)	0	1/20 (5%)	1
Investigations
International normalized ratio increased	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	1/19 (5.3%)	1	0/20 (0%)	0
Other (Not Including Serious) Adverse Events
	Dose escalation_Cohort 1_200 mg		Dose escalation_Cohort 2_400 mg		Dose escalation_Cohort 3_800 mg (Fasting)		Dose escalation_Cohort 4_800 mg (Fed)		Dose expansion_PTCL_800 mg (Fasting)		Dose expansion_CTCL_800 mg (Fasting)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		3/4 (75%)		5/5 (100%)		5/6 (83.3%)		11/19 (57.9%)		17/20 (85%)
Blood and lymphatic system disorders
Anemia	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	1/6 (16.7%)	1	1/19 (5.3%)	1	1/20 (5%)	1
Neutropenia	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	2/6 (33.3%)	2	0/19 (0%)	0	1/20 (5%)	1
Gastrointestinal disorders
Diarrhoea	1/4 (25%)	2	0/4 (0%)	0	1/5 (20%)	1	1/6 (16.7%)	1	2/19 (10.5%)	2	7/20 (35%)	8
Dyspepsia	0/4 (0%)	0	0/4 (0%)	0	1/5 (20%)	1	0/6 (0%)	0	0/19 (0%)	0	2/20 (10%)	2
Nausea	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	1/6 (16.7%)	2	0/19 (0%)	0	2/20 (10%)	2
Vomiting	1/4 (25%)	2	1/4 (25%)	1	0/5 (0%)	0	0/6 (0%)	0	0/19 (0%)	0	1/20 (5%)	1
General disorders
Fatigue	0/4 (0%)	0	1/4 (25%)	1	0/5 (0%)	0	1/6 (16.7%)	1	1/19 (5.3%)	1	6/20 (30%)	6
Pyrexia	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	1/19 (5.3%)	3	2/20 (10%)	2
Investigations
Alanine aminotransferase increased	1/4 (25%)	2	0/4 (0%)	0	2/5 (40%)	3	3/6 (50%)	3	4/19 (21.1%)	5	8/20 (40%)	13
Aspartate aminotransferase increased	1/4 (25%)	3	0/4 (0%)	0	2/5 (40%)	2	3/6 (50%)	10	4/19 (21.1%)	5	8/20 (40%)	15
Gamma-glutamyltransferase increased	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	2/6 (33.3%)	2	0/19 (0%)	0	5/20 (25%)	7
Blood thyroid stimulating hormone increased	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	2/6 (33.3%)	2	0/19 (0%)	0	2/20 (10%)	3
Blood alkaline phosphatase increased	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	1/6 (16.7%)	1	0/19 (0%)	0	2/20 (10%)	2
Metabolism and nutrition disorders
Dehydration	0/4 (0%)	0	1/4 (25%)	1	0/5 (0%)	0	0/6 (0%)	0	1/19 (5.3%)	1	2/20 (10%)	2
Musculoskeletal and connective tissue disorders
Muscle spasms	0/4 (0%)	0	0/4 (0%)	0	1/5 (20%)	1	1/6 (16.7%)	2	0/19 (0%)	0	3/20 (15%)	3
Nervous system disorders
Dizziness	0/4 (0%)	0	0/4 (0%)	0	1/5 (20%)	1	1/6 (16.7%)	1	0/19 (0%)	0	3/20 (15%)	3
Headache	1/4 (25%)	1	0/4 (0%)	0	1/5 (20%)	1	1/6 (16.7%)	2	0/19 (0%)	0	2/20 (10%)	2
Skin and subcutaneous tissue disorders
Rash	1/4 (25%)	1	0/4 (0%)	0	0/5 (0%)	0	1/6 (16.7%)	1	1/19 (5.3%)	1	2/20 (10%)	2
Pruritis	1/4 (25%)	1	0/4 (0%)	0	0/5 (0%)	0	0/6 (0%)	0	0/19 (0%)	0	3/20 (15%)	3
Erythema	0/4 (0%)	0	0/4 (0%)	0	0/5 (0%)	0	1/6 (16.7%)	1	0/19 (0%)	0	2/20 (10%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS 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.