Study of Lenalidomide and Ofatumumab for the Treatment of Relapsed or Refractory Non-Hodgkin's Lymphoma

• Sponsor: University of Nebraska (Other)
• Overall Status: Completed
• CT.gov ID: NCT01060384
• Collaborator: Celgene Corporation (Industry), GlaxoSmithKline (Industry)
• Enrollment: 46
• Locations: 2
• Arm: 1
• Duration (Months): 94.1
• Patients Per Site: 23
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this trial is to investigate the efficacy (how well the drug works) of ofatumumab and lenalidomide in patients with lymphoma and to investigate if any possible unwanted side effects may occur. The purpose of the Phase I portion of this trial will be to determine the maximum dose of these medications that can be given with minimal side effects.

Condition or Disease	Intervention/Treatment	Phase
Non-Hodgkin's Lymphoma	Drug: Lenalidomide; Drug: ofatumumab	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I/II Study of Lenalidomide and Ofatumumab for the Treatment of Relapsed or Refractory Non-Hodgkin's Lymphoma
• Study Start Date: Mar 1, 2010
• Actual Primary Completion Date: Oct 25, 2016
• Actual Study Completion Date: Jan 1, 2018

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Phase 1/Phase II All participants will receive the same dose of Ofatumumab. There will be three planned dose cohorts for the Lenalidomide in the Phase 1 portion of this trial. A maximum of 18 patients will be enrolled in to Phase 1. Three evaluable patients will be enrolled in to each of the dose cohorts with an additional 3 patients to be enrolled in the maximum tolerated dose (MTD). An additional 29 evaluable patients will be enrolled in to Phase II using the MTD for Lenalidomide that was determined in Phase 1.

Drug: Lenalidomide; Dose Cohort -1^ 10mg daily on Days 1-21 every 28 days Dose Cohort +1^^ 15mg daily on Days 1-21, every 28 days Dose Cohort +2 20 mg daily on Days 1-21, every 28 days Dose Cohort #3 25 mg daily on Days 1-21, every 28 days ^Used only if Dose Cohort +1 requires further reduction ^^Starting Dose Cohort in Phase I; Drug: ofatumumab; 8 weekly infusions of ofatumumab 1000mg.

Outcome Measures

Primary Outcome Measures

1. Phase I: Maximum Tolerated Dose (MTD) of Lenalidomide [7 months]

   The maximum tolerated dose (MTD) will be defined as the next lowest dose cohort below where ≥ 2/3 or ≥ 3/6 patients experience dose limiting toxicities in cycle 1.

Secondary Outcome Measures

1. Phase I and Phase II: Event Free Survival and Overall Survival [2 years from start of treatment]

   Event free survival is defined as the time from start of treatment to disease progression or death from any cause. Overall survival (OS) is defined as the time from start of treatment to death from any cause. A response-evaluable subject will be considered anyone who completes at least 2 cycles of therapy with documented response or documented progression of disease after at least one complete cycle of therapy but, prior to 2 complete cycles of therapy. A response-evaluable subject will be considered anyone who completes at least 2 cycles of therapy with documented response or documented progression of disease after at least one complete cycle of therapy but, prior to 2 complete cycles of therapy. A non-evaluable subject will be one who receives less than one complete cycle of therapy (ie. 4 infusions of ofatumumab and 21 days of lenalidomide). A non-evaluable subject will also be one that has no documented response prior to treatment withdrawal.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically confirmed diagnosis of CD20+ non-Hodgkin's lymphoma that is recurrent or refractory after at least one prior therapy and for which no other potentially curative therapy is available.

• Subject, age > or = 19 years

• Patients must have relapsed or refractory disease after at least one prior systemic therapy, with at least a 3 week interval from the completion of the most recent chemotherapy or radiotherapy regimen (unless the patient has had progressive disease prior to the 3 weeks). Patient has resolved all toxicities to ≤ grade 1, felt to be related to prior therapy.

• Patients must be ineligible or relapsed after an autologous or allogeneic stem cell transplant if clinically appropriate.

• Adequate Laboratory Parameters:

• ANC ≥ 1500/μL

• Platelet count ≥75,000/μL

• Total bilirubin ≤ 1.5 times the institutional Upper Limit of Normal (ULN)- unless due to NHL

• Hepatic enzymes (AST, ALT ) ≤ 2.5 times the institutional ULN - unless due to NHL

• Serum Creatinine < 3.0 times the institutional ULN - unless due to NHL

• Creatinine clearance ≥60ml/min during phase I (See Appendix A) Creatinine clearance ≥ 30ml/min during phase II and patients with creatinine clearance ≥ 30ml/min and < 60ml/min should start Lenalidomide at a reduced dose. See Section 5.3.1

• Females of child-bearing potential (FCBP) must agree to:

Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours prior to prescribing lenalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. See Appendix B: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods.

Note: A FCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally postmenopausal (i.e., amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).

Male patients must:

• Agree to use a condom during sexual contact with a FCBP, even if they have had a vasectomy, throughout study drug therapy, during any dose interruption and 28 days after cessation of study therapy.

• Agree to not donate semen during study drug therapy and for a period after end of study drug therapy

• ECOG Performance status of 0-2 (See Appendix C)

• Signed written informed consent including HIPAA according to institutional guidelines

Exclusion Criteria:

• No malignancy [other than the one treated in this study] which required systemic treatment within the past 3 years.

• Patients not willing to take DVT prophylaxis

• Pregnant or lactating females

• Positive serology for hepatitis B (HB) defined as positive test of HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA test will be performed and if positive the subject will be excluded. Patients with documented vaccination against Hepatitis B will not be considered positive.

• Known seropositive for active viral infection with human immunodeficiency virus (HIV), or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine are eligible.

• Patients with ≥ Grade 2 neuropathy

• Active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)

• Known CNS involvement with lymphoma

• Significant concurrent, uncontrolled medical condition, that in the judgment of the investigator, may affect the patient's ability to sign the informed consent and comply with study procedures.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Saint Francis Medical Center	Grand Island	Nebraska	United States	68803
2	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198

Sponsors and Collaborators

• University of Nebraska
• Celgene Corporation
• GlaxoSmithKline

Investigators

• Principal Investigator: Julie M Vose, University of Nebraska

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Julie M Vose, MD, Professor, University of Nebraska
• ClinicalTrials.gov Identifier: NCT01060384
• Other Study ID Numbers: 514-09-FB
• First Posted: Feb 2, 2010
• Last Update Posted: Mar 5, 2019
• Last Verified: Feb 1, 2019

• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lenalidomide; Ofatumumab

Study Results

Participant Flow

Recruitment Details	All the patients will receive 8 weekly infusions of Ofatumumab 1000mg. Dose escalation of Lenalidomide planned in three dose cohorts. Dose reduction Cohort (-1) will be added if severe adverse events noted in 2/3 patients. Phase II will evaluate Lenalidomide at maximum tolerated dose (MTD) and Ofatumumab in 36 patients.

Arm/Group Title	Phase 1: Cohort -1	Phase 1: Cohort #1	Phase 1: Cohort #2	Phase 1: Cohort #3	Phase II: Event Free Survival and Overall Survival
Arm/Group Description	Cohort -1 received 10 mg Lenalidomide per day on days 1-21 every 28 days.	Cohort 1 received 15 mg Lenalidomide per day on days 1-21 every 28 days.	Cohort 2 received 20 mg Lenalidomide on days 1-21 every 28 days.	Cohort 3 received 25 mg Lenalidomide per day on days 1-21 every 28 days.	Event free and overall survival probabilities will be computed on all patients receiving the MTD dose, including those patients in the phase I portion of the study.
Period Title: Overall Study
STARTED	6	4	0	0	36
COMPLETED	6	3	0	0	34
NOT COMPLETED	0	1	0	0	2

Baseline Characteristics

Arm/Group Title	Phase 1/Phase II
Arm/Group Description	There will be three planned dose cohorts for the Lenalidomide in the Phase 1 portion of this trial. Three evaluable patients will be enrolled in to each of the dose cohorts with an additional 3 patients to be enrolled in the maximum tolerated dose (MTD). Patients will be enrolled in to Phase II using the MTD for Lenalidomide that was determined in Phase 1. Dose Cohort -1: 10 mg per day. This cohort will be used only if needed due to dose reduction in Dose cohort +1. Dose Cohort +1: 15 mg per day. Dose Cohort +2: 20 mg per day. Dose Cohort +3: 25 mg per day. Phase II: An additional 29 response-evaluable patients will be enrolled into Phase II using the MTD for Lenalidomide that was determined in Phase 1. All subjects will receive the same dosing schedule for Ofatumumab regardless of which Phase of the trial they are enrolled.
Overall Participants	46
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	63.4
Sex: Female, Male (Count of Participants)
Female	13 28.3%
Male	33 71.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	46 100%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	46 100%

Outcome Measures

1. Primary Outcome

Title	Phase I: Maximum Tolerated Dose (MTD) of Lenalidomide
Description	The maximum tolerated dose (MTD) will be defined as the next lowest dose cohort below where ≥ 2/3 or ≥ 3/6 patients experience dose limiting toxicities in cycle 1.
Time Frame	7 months

Outcome Measure Data

Analysis Population Description

Ten patients were enrolled in Phase 1. One patient was inevaluable, thus 9 patients are evaluable for outcome. Patients will be evaluable for Dose Limiting Toxicity (DLT) if they receive at least 75% of the planned doses of study drugs or they experience DLT in cycle 1 or and have sufficient followup data to determine whether DLT occurred.

Arm/Group Title	Phase 1
Arm/Group Description	Maximum Tolerated Dose (MTD) of Lenalidomide
Measure Participants	9
Number [milligrams]	10

2. Secondary Outcome

Title	Phase I and Phase II: Event Free Survival and Overall Survival
Description	Event free survival is defined as the time from start of treatment to disease progression or death from any cause. Overall survival (OS) is defined as the time from start of treatment to death from any cause. A response-evaluable subject will be considered anyone who completes at least 2 cycles of therapy with documented response or documented progression of disease after at least one complete cycle of therapy but, prior to 2 complete cycles of therapy. A response-evaluable subject will be considered anyone who completes at least 2 cycles of therapy with documented response or documented progression of disease after at least one complete cycle of therapy but, prior to 2 complete cycles of therapy. A non-evaluable subject will be one who receives less than one complete cycle of therapy (ie. 4 infusions of ofatumumab and 21 days of lenalidomide). A non-evaluable subject will also be one that has no documented response prior to treatment withdrawal.
Time Frame	2 years from start of treatment

Outcome Measure Data

Analysis Population Description

Six patients in Phase 1 were treated at the MTD and 34 patients enrolled in Phase II were eligible for evaluation. Data was analyzed for all patients treated at the MTD (n=40).

Arm/Group Title	Phase II: Lemalidomide at MTD and Ofatumumab
Arm/Group Description	Event free and overall survival probabilities will be computed on all patients receiving the MTD dose, including those patients in the phase I portion of the study.
Measure Participants	40
Estimated 1 year Event Free Survival	38 82.6%
Estimated 1 year Overall Survival	53 115.2%
Estimated 2 year Event Free Survival	20 43.5%
Estimated 2 year Overall Survival	44 95.7%

Adverse Events

Time Frame	6 years
Arm/Group Title	Phase I: Cohort -1		Phase 1: Cohort #1		Phase 1: Cohort #2		Phase 1: Cohort #3		Phase 1 and Phase II: Event Free Survival and Overall Survival
Arm/Group Description	Lenalidomide: 10 mg per day.		Lenalidomide: 15mg per day.		Lenalidomide: 20mg per day.		Lenalidomide: 25 mg per day.		Lenalidomide at maximum tolerated dose (MTD).
All Cause Mortality
	Phase I: Cohort -1		Phase 1: Cohort #1		Phase 1: Cohort #2		Phase 1: Cohort #3		Phase 1 and Phase II: Event Free Survival and Overall Survival
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/6 (16.7%)		1/4 (25%)		0/0 (NaN)		0/0 (NaN)		6/36 (16.7%)
Serious Adverse Events
	Phase I: Cohort -1		Phase 1: Cohort #1		Phase 1: Cohort #2		Phase 1: Cohort #3		Phase 1 and Phase II: Event Free Survival and Overall Survival
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/6 (66.7%)		3/4 (75%)		0/0 (NaN)		0/0 (NaN)		14/36 (38.9%)
Blood and lymphatic system disorders
Febrile neutropenia	0/6 (0%)	0	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0	0/36 (0%)	0
Platelet count decreased	1/6 (16.7%)	1	0/4 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	1/36 (2.8%)	1
Cardiac disorders
Chest pain	0/6 (0%)	0	0/4 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	1/36 (2.8%)	1
Myocardial infarction	0/6 (0%)	0	0/4 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	1/36 (2.8%)	1
Atrial flutter	0/6 (0%)	0	0/4 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	1/36 (2.8%)	1
Atrial fibrillation	0/6 (0%)	0	0/4 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	1/36 (2.8%)	1
Cardiac arrest	0/6 (0%)	0	0/4 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	1/36 (2.8%)	1
Aortic valve disease	0/6 (0%)	0	0/4 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	1/36 (2.8%)	1
Left ventricular systolic dysfunction	0/6 (0%)	0	0/4 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	1/36 (2.8%)	1
Gastrointestinal disorders
Dysphagia	0/6 (0%)	0	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0	0/36 (0%)	0
Abdominal Pain	0/6 (0%)	0	0/4 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	1/36 (2.8%)	1
Nausea	1/6 (16.7%)	2	0/4 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	1/36 (2.8%)	1
General disorders
Fever	0/6 (0%)	0	2/4 (50%)	6	0/0 (NaN)	0	0/0 (NaN)	0	2/36 (5.6%)	3
Weakness	0/6 (0%)	0	0/4 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	3/36 (8.3%)	3
Fatigue	0/6 (0%)	0	0/4 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	2/36 (5.6%)	2
Hepatobiliary disorders
Cholecystitis	1/6 (16.7%)	1	0/4 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/36 (0%)	0
Infections and infestations
Infections and infestations - Other, specify	0/6 (0%)	0	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0	1/36 (2.8%)	1
Infections and infestations - Other, specify	0/6 (0%)	0	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0	0/36 (0%)	0
Infections and infestations - Other, specify	0/6 (0%)	0	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0	0/36 (0%)	0
sepsis	0/6 (0%)	0	0/4 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	1/36 (2.8%)	1
Infections and infestations - Other, specify	1/6 (16.7%)	1	0/4 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/36 (0%)	0
Infections and infestations - Other, specify	0/6 (0%)	0	0/4 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	1/36 (2.8%)	1
Infections and infestations - Other, specify	1/6 (16.7%)	1	0/4 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	1/36 (2.8%)	1
Injury, poisoning and procedural complications
Injury, poisoning and prcedural complications - Other, specify	1/6 (16.7%)	1	0/4 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/36 (0%)	0
Vascular access complication	0/6 (0%)	0	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0	0/36 (0%)	0
Injury, poisoning and procedural complications - Other, specify	0/6 (0%)	0	0/4 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	1/36 (2.8%)	1
Investigations
Neutrophil count decreased	0/6 (0%)	0	2/4 (50%)	2	0/0 (NaN)	0	0/0 (NaN)	0	0/36 (0%)	0
Neutrophil count decreased	1/6 (16.7%)	1	2/4 (50%)	2	0/0 (NaN)	0	0/0 (NaN)	0	2/36 (5.6%)	2
Metabolism and nutrition disorders
Acidosis	0/6 (0%)	0	0/4 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	1/36 (2.8%)	1
Hypokalemia	0/6 (0%)	0	0/4 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	1/36 (2.8%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	0/6 (0%)	0	0/4 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	1/36 (2.8%)	2
Nervous system disorders
Stroke	1/6 (16.7%)	1	0/4 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/36 (0%)	0
Ataxia	0/6 (0%)	0	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0	0/36 (0%)	0
Nervous system disorders - )ther, specify	0/6 (0%)	0	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0	0/36 (0%)	0
Encephalopathy	0/6 (0%)	0	0/4 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	1/36 (2.8%)	2
Psychiatric disorders
confusion	1/6 (16.7%)	2	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0	1/36 (2.8%)	2
Renal and urinary disorders
Renal and urinary disorders - Other, specify	0/6 (0%)	0	0/4 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	1/36 (2.8%)	2
Reproductive system and breast disorders
Testicular pain	1/6 (16.7%)	1	0/4 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/36 (0%)	0
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and medicastinal disorders - Other, specify	0/6 (0%)	0	0/4 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	1/36 (2.8%)	1
Respiratory Failure	0/6 (0%)	0	0/4 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	1/36 (2.8%)	1
Pleural effusion	0/6 (0%)	0	0/4 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	1/36 (2.8%)	1
Cough	0/6 (0%)	0	0/4 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	1/36 (2.8%)	1
Respiatory, thoracic and mediastinal disorders - Other, specify	0/6 (0%)	0	0/4 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	1/36 (2.8%)	1
Other (Not Including Serious) Adverse Events
	Phase I: Cohort -1		Phase 1: Cohort #1		Phase 1: Cohort #2		Phase 1: Cohort #3		Phase 1 and Phase II: Event Free Survival and Overall Survival
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100%)		4/4 (100%)		0/0 (NaN)		0/0 (NaN)		18/36 (50%)
General disorders
Infusion related reaction	0/6 (0%)	0	0/4 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	3/36 (8.3%)	3
Fatigue	1/6 (16.7%)	1	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0	0/36 (0%)	0
Investigations
Neutrophil count decreased	3/6 (50%)	22	4/4 (100%)	20	0/0 (NaN)	0	0/0 (NaN)	0	16/36 (44.4%)	45
Platelet count decreased	1/6 (16.7%)	2	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0	2/36 (5.6%)	2
White blood cell decreased	1/6 (16.7%)	4	2/4 (50%)	2	0/0 (NaN)	0	0/0 (NaN)	0	0/36 (0%)	0
Investigations - Other, specify	1/6 (16.7%)	5	0/4 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/36 (0%)	0
Investigations - Other, specify	0/6 (0%)	0	0/4 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	2/36 (5.6%)	2
Metabolism and nutrition disorders
Hypokalemia	0/6 (0%)	0	1/4 (25%)	1	0/0 (NaN)	0	0/0 (NaN)	0	0/36 (0%)	0

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.