PNT2258 for Treatment of Patients With Richter's Transformation (Brighton)

• Sponsor: Sierra Oncology, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02378038
• Collaborator: (none)
• Enrollment: 5
• Locations: 9
• Arm: 1
• Duration (Months): 10
• Patients Per Site: 0.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study is sponsored by Sierra Oncology, Inc. formerly ProNAi Therapeutics, Inc. It is a multi-center, single-arm, 2-stage, open-label phase II investigation of PNT2258 to characterize anti-tumor activity and collect safety data on patients with Richter's Transformation.

Condition or Disease	Intervention/Treatment	Phase
Richter's Transformation	Drug: PNT2258	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of PNT2258 in Patients With Richter's Transformation (RT)
• Study Start Date: Aug 1, 2015
• Actual Primary Completion Date: Jun 1, 2016
• Actual Study Completion Date: Jun 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PNT2258 PNT2258 will be administered at 120 mg/m2 on days 1-5 of a 21-day cycle for 8 induction cycles followed by continuation phase therapy at a dose of 100 mg/m2 on days 1-4 of a 28-day cycle.	Drug: PNT2258

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate [2 months]

   Proportion of subjects with complete response (CR/CMR) or partial response (PR/PMR)

Secondary Outcome Measures

1. Disease Control Rate [2 months]

   Proportion of subjects with stable disease or better (CR/CMR, PR/PMR or SD/NMR)

2. Duration of Overall Response [2 months]

3. Time to Response [2 months]

4. Progression Free Survival [2 months]

5. Overall Survival [2 months]

6. Safety - Assessment of Adverse Events [2 months]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Histologically confirmed Richter's transformation (RT) from chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

2. Availability of fresh or archived tumor tissue.

3. FDG PET-CT (disease) positive baseline scan with measurable disease.

4. ECOG performance status of 0-1.

5. Evidence of disease progression at study entry.

6. Discontinuation of prior anticancer therapy for ≥ 7 days prior to C1D1 and recovered to ≤ CTCAE grade 2 (or baseline) from any acute or chronic toxicity associated with prior therapy.

7. Must have previously received at least one prior chemotherapeutic regimen for RT.

• Previously untreated RT patients deemed ineligible for, or that refuse, intensive chemotherapy are eligible.

1. Adequate bone marrow, renal, and hepatic function.

2. Normal Coagulation profile.

3. Agreement to use acceptable methods of contraception during the study and for ≥ 120 days after the last dose of PNT2258 if sexually active and able to bear or beget children.

4. Ability to participate in the clinical study for a minimum of at least 2 cycles (6 weeks).

Exclusion Criteria:

1. Concurrent non-hematologic malignancies requiring treatment.

2. No more than 2 prior regimens for DLBCL.

3. Hodgkin's variant of Richter's lymphoma, accelerated CLL, composite lymphoma, interdigitating dendritic cell sarcoma, sarcoma, EBV-associated lymphoma or prolymphocytic transformation.

4. Ongoing risk of bleeding.

5. CNS or leptomeningeal involvement of lymphoma

6. Concurrent clinically significant illness, medical condition, surgical history, physical finding, electrocardiogram or laboratory finding that, in the opinion of the investigator, could adversely affect the safety of the subject or impair the assessment of the study results.

7. Pregnancy or breast-feeding.

8. Previous exposure to PNT2258.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UC Irvine Medical Center	Orange	California	United States	92868
2	Northwestern University Feinberg School of Medicine	Chicago	Illinois	United States	60611
3	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
4	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
5	Columbia University Medical Center	New York	New York	United States	10027
6	Duke University	Durham	North Carolina	United States	27705
7	University of Pennsylvania, Abramson Cancer Center	Philadelphia	Pennsylvania	United States	19104
8	Tyler Hematology Oncology	Tyler	Texas	United States	75701
9	Swedish Cancer Institute	Seattle	Washington	United States	98122

Sponsors and Collaborators

• Sierra Oncology, Inc.

Investigators

• Study Chair: Barbara Klencke, MD, Sierra Oncology, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sierra Oncology, Inc.
• ClinicalTrials.gov Identifier: NCT02378038
• Other Study ID Numbers: PNT2258-04-Richter's
• First Posted: Mar 4, 2015
• Last Update Posted: Mar 10, 2020
• Last Verified: Jan 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Sierra Oncology, Inc.: PNT2258; Richter's Transformation; NHL; Non-Hodgkin's Lymphoma; Lymphoma; DLBCL; Diffuse Large B-cell Lymphoma; Lymphoma, Large B-cell, Diffuse; Lymphoma, Non-Hodgkin; Lymphoma, B-cell

Study Results

Participant Flow

Recruitment Details	The study was initiated in August 2015 and the first subject was enrolled on 27 October 2015. Enrollment was closed as of 07 June 2016. Subjects were enrolled at oncology clinics in the USA.

Arm/Group Title	PNT2258
Arm/Group Description	PNT2258 administered at 120 mg/m2 on days 1-5 of a 21-day cycle for 8 induction cycles followed by continuation phase therapy at a dose of 100 mg/m2 on days 1-4 of a 28-day cycle.
Period Title: Overall Study
STARTED	5
COMPLETED	0
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	PNT2258
Arm/Group Description	PNT2258 administered at 120 mg/m2 on days 1-5 of a 21-day cycle for 8 induction cycles followed by continuation phase therapy at a dose of 100 mg/m2 on days 1-4 of a 28-day cycle.
Overall Participants	5
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	73
Sex: Female, Male (Count of Participants)
Female	2 40%
Male	3 60%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate
Description	Proportion of subjects with complete response (CR/CMR) or partial response (PR/PMR)
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PNT2258
Arm/Group Description	PNT2258 administered at 120 mg/m2 on days 1-5 of a 21-day cycle for 8 induction cycles followed by continuation phase therapy at a dose of 100 mg/m2 on days 1-4 of a 28-day cycle.
Measure Participants	5
Count of Participants [Participants]	0 0%

2. Secondary Outcome

Title	Disease Control Rate
Description	Proportion of subjects with stable disease or better (CR/CMR, PR/PMR or SD/NMR)
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PNT2258
Arm/Group Description	PNT2258 administered at 120 mg/m2 on days 1-5 of a 21-day cycle for 8 induction cycles followed by continuation phase therapy at a dose of 100 mg/m2 on days 1-4 of a 28-day cycle.
Measure Participants	5
Count of Participants [Participants]	0 0%

3. Secondary Outcome

Title	Duration of Overall Response
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

Analysis not performed as there were no responders.

Arm/Group Title	PNT2258
Arm/Group Description	PNT2258 administered at 120 mg/m2 on days 1-5 of a 21-day cycle for 8 induction cycles followed by continuation phase therapy at a dose of 100 mg/m2 on days 1-4 of a 28-day cycle.
Measure Participants	0

4. Secondary Outcome

Title	Time to Response
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

Analysis not performed as there were no responders.

Arm/Group Title	PNT2258
Arm/Group Description	PNT2258 administered at 120 mg/m2 on days 1-5 of a 21-day cycle for 8 induction cycles followed by continuation phase therapy at a dose of 100 mg/m2 on days 1-4 of a 28-day cycle.
Measure Participants	0

5. Secondary Outcome

Title	Progression Free Survival
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

Analysis not performed as the study was terminated.

Arm/Group Title	PNT2258
Arm/Group Description	PNT2258 administered at 120 mg/m2 on days 1-5 of a 21-day cycle for 8 induction cycles followed by continuation phase therapy at a dose of 100 mg/m2 on days 1-4 of a 28-day cycle.
Measure Participants	0

6. Secondary Outcome

Title	Overall Survival
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

Analysis not performed as the study was terminated.

Arm/Group Title	PNT2258
Arm/Group Description	PNT2258 administered at 120 mg/m2 on days 1-5 of a 21-day cycle for 8 induction cycles followed by continuation phase therapy at a dose of 100 mg/m2 on days 1-4 of a 28-day cycle.
Measure Participants	0

7. Secondary Outcome

Title	Safety - Assessment of Adverse Events
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PNT2258
Arm/Group Description	PNT2258 administered at 120 mg/m2 on days 1-5 of a 21-day cycle for 8 induction cycles followed by continuation phase therapy at a dose of 100 mg/m2 on days 1-4 of a 28-day cycle.
Measure Participants	5
Number [participants reporting at least 1 AE]	5 100%

Adverse Events

Time Frame	From the first dose of PNT2258 until 30 days after the last dose of PNT2258
Arm/Group Title	PNT2258
Arm/Group Description	PNT2258 administered at 120 mg/m2 on days 1-5 of a 21-day cycle for 8 induction cycles followed by continuation phase therapy at a dose of 100 mg/m2 on days 1-4 of a 28-day cycle.
All Cause Mortality
	PNT2258
	Affected / at Risk (%)	# Events
Total	2/5 (40%)
Serious Adverse Events
	PNT2258
	Affected / at Risk (%)	# Events
Total	4/5 (80%)
Cardiac disorders
Atrial fibrillation	1/5 (20%)
Cardiomyopathy	1/5 (20%)
General disorders
Pyrexia	1/5 (20%)
Disease progression	1/5 (20%)
Infections and infestations
Listeriosis	1/5 (20%)
Pneumonia	1/5 (20%)
Metabolism and nutrition disorders
Hypercalcaemia	1/5 (20%)
Nervous system disorders
Haemorrhage intracranial	1/5 (20%)
Other (Not Including Serious) Adverse Events
	PNT2258
	Affected / at Risk (%)	# Events
Total	5/5 (100%)
Blood and lymphatic system disorders
Anaemia	2/5 (40%)
Ear and labyrinth disorders
Hearing impaired	1/5 (20%)
Gastrointestinal disorders
Abdominal pain	1/5 (20%)
Diarrhoea	2/5 (40%)
Faecal incontinence	1/5 (20%)
Nausea	1/5 (20%)
Toothache	1/5 (20%)
General disorders
Chest discomfort	1/5 (20%)
Chest pain	2/5 (40%)
Chills	1/5 (20%)
Early satiety	1/5 (20%)
Fatigue	3/5 (60%)
Oedema peripheral	2/5 (40%)
Pain	1/5 (20%)
Infections and infestations
Cytomegalovirus viraemia	1/5 (20%)
Urinary tract infection	1/5 (20%)
Injury, poisoning and procedural complications
Infusion related reaction	1/5 (20%)
Investigations
Alanine aminotransferase increased	1/5 (20%)
Aspartate aminotransferase increased	1/5 (20%)
Blood alkaline phosphatase increased	1/5 (20%)
Blood bilirubin increased	1/5 (20%)
Blood creatinine increased	1/5 (20%)
Blood phosphorus decreased	1/5 (20%)
Neutrophil count decreased	1/5 (20%)
Platelet count decreased	2/5 (40%)
White blood cell count decreased	1/5 (20%)
Metabolism and nutrition disorders
Decreased appetite	1/5 (20%)
Dehydration	1/5 (20%)
Fluid overload	1/5 (20%)
Hyperglycaemia	1/5 (20%)
Hypermagnesaemia	1/5 (20%)
Hypokalaemia	2/5 (40%)
Hypomagnesaemia	1/5 (20%)
Hypophosphataemia	2/5 (40%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/5 (20%)
Joint stiffness	1/5 (20%)
Muscular weakness	1/5 (20%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain	1/5 (20%)
Nervous system disorders
Dizziness	1/5 (20%)
Dysgeusia	1/5 (20%)
Peripheral sensory neuropathy	1/5 (20%)
Psychiatric disorders
Confusional state	1/5 (20%)
Insomnia	1/5 (20%)
Renal and urinary disorders
Urinary incontinence	1/5 (20%)
Respiratory, thoracic and mediastinal disorders
Cough	1/5 (20%)
Dyspnoea	1/5 (20%)
Haemoptysis	1/5 (20%)
Pleural effusion	1/5 (20%)
Pulmonary hypertension	1/5 (20%)
Pulmonary oedema	1/5 (20%)
Skin and subcutaneous tissue disorders
Decubitus ulcer	1/5 (20%)
Pruritus	2/5 (40%)
Urticaria	1/5 (20%)
Vascular disorders
Embolism	1/5 (20%)
Hypertension	2/5 (40%)
Hypotension	1/5 (20%)

Limitations/Caveats

Early termination of enrollment, and thus very few subjects were analyzed.

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.