Melphalan and Panobinostat (LBH589) for the Treatment of Patients With Recurrent Multiple Myeloma

• Sponsor: Oncotherapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00743288
• Collaborator: Novartis (Industry)
• Enrollment: 40
• Locations: 4
• Arm: 1
• Duration (Months): 53
• Patients Per Site: 10
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Panobinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving melphalan together with panobinostat may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of melphalan when given together with panobinostat in treating patients with recurrent multiple myeloma.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Melphalan; Drug: Panobinostat	Phase 1/Phase 2

Detailed Description

OBJECTIVES:

Primary

• To establish the maximum tolerated dose (MTD) and determine the dose-limiting toxicities (DLT) of panobinostat in combination with melphalan in patients with relapsed or refractory multiple myeloma. (Phase I)

• To determine the dose of this regimen to be used in the Phase II portion of the study. (Phase I)

• To determine the efficacy as evidenced by the response rate (combined complete response, very good partial response, partial response, and minimal response) in patients treated with this regimen. (Phase II)

Secondary

• To obtain preliminary evidence of efficacy of the combination of LBH589 and melphalan for patients with relapsed or refractory multiple myeloma. (Phase I)

• To determine the safety and tolerability of this regimen in these patients. (Phase II)

• To determine time to disease progression, time to response, and duration of response in patients treated with this regimen. (Phase II)

• To determine progression-free survival and overall survival of patients treated with this regimen. (Phase II)

OUTLINE: This is a multicenter, phase I, dose-escalation study followed by a phase II study.

Patients receive oral panobinostat once daily on days 1, 3, 5, 8, 10, and 12 and oral melphalan once daily on days 1, 3 and 5. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II Study of Oral Melphalan Combined With LBH589 for Patients With Relapsed or Refractory Multiple Myeloma (MM)
• Study Start Date: Jul 1, 2008
• Actual Primary Completion Date: Nov 1, 2012
• Actual Study Completion Date: Dec 1, 2012

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Melphalan and Panobinostat Schedule A: 10mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1-4 of a 28-day cycle and melphalan PO at 0.05 mg/kg on days 1-5 of week 1. Toxicity led to the following changes in dose and schedule Schedule B1: 10mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1-4 and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1. Schedule B2: 20mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1-4 and 0.05 mg/kg melphalan POon days 1, 3 and 5 of week 1. Schedule C: 20mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1 and 2 and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1 Schedule D1: 15 mg/daily LBH589 PO and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1. Schedule D2: 15 mg/daily LBH589 PO and 0.10 mg/kg melphalan PO on days 1, 3 and 5 of week 1. Schedule D3: 20 mg/daily LBH589 PO and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1.

Drug: Melphalan; Same as above; Other Names: Phenylalanine mustard, Alkeran ; Drug: Panobinostat; Other Names: LBH589

Outcome Measures

Primary Outcome Measures

1. Maximum Tolerated Dose (MTD) [12 months]

   Phase 1: to determine the MTD of panobinostat (LBH589) in combination with melphalan to be used in the Phase 2 portion of the study

2. MTD [12 months]

   Phase 1: to determine MTD of melphalan in combination with panobinostat to be used in the Phase 2 portion of the study

3. Overall Response Rate (ORR) and Clinical Benefit Rate (CBR) [ORR= Complete Response (CR) + Very Good Partial Response (VGPR) + Partial Response (PR)]; CBR=ORR + Minimal Response (MR)] Following Treatment With Panobinostat and Melphalan [24 months]

   Responses were evaluated according to criteria modified from those developed by Blade et al., 1998 The reference point for evaluating response improvement is the baseline. This baseline reference point is also valid when a patient has already achieved a response and transitions through into a better response grade.

Secondary Outcome Measures

1. Duration of Response [First evidence of PR or better (for overall response) and MR or better (for clinical benefit response) to start of disease progression or death]

2. Time to Progression [Time from the start of treatment to progressive disease]

Eligibility Criteria

Criteria

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

Inclusion criteria:

• Diagnosis of multiple myeloma, based on the following criteria:

• Major criteria

• Plasmacytomas on tissue biopsy (1)

• Bone marrow plasmacytosis (> 30% plasma cells) (2)

• Monoclonal immunoglobulin (Ig) spike on serum electrophoresis, IgG > 3.5 g/dL or IgA > 2.0 g/dL, and kappa or lambda light chain excretion > 1 g/day on 24-hour urine protein electrophoresis (3)

• Minor Criteria

• Bone marrow plasmacytosis (10-30% plasma cells) (a)

• Monoclonal immunoglobulin present but of lesser magnitude than given under major criteria (b)

• Lytic bone lesions ©)

• Normal IgM < 50 mg/dL, IgA < 100 mg/dL, or IgG < 600 mg/dL (d)

• Meets any of the following sets of multiple myeloma diagnostic criteria:

• Any two of the major criteria

• Major criterion 1 plus minor criterion b, c, or d

• Major criterion 3 plus minor criterion a or c

• Minor criteria a, b, and c, OR a, b, and d

• Measurable disease, defined as a monoclonal immunoglobulin spike on serum electrophoresis of ≥ 1 g/dL and/or urine monoclonal immunoglobulin spike of ≥ 200 mg/24 hours, or evidence of lytic bone disease

• Must have received ≥ 1 prior treatment regimen OR refractory to most recent chemotherapy

• Relapsed following stabilization or response to standard first-line chemotherapy (e.g., vincristine, doxorubicin hydrochloride, and prednisone or melphalan and prednisone) or first-line high-dose chemotherapy

• Refractory (i.e., failure to achieve at least complete or partial response or stable disease) to most recent chemotherapy, whether or not containing systemic corticosteroids

• Prior treatment with ≤ 4 days of a total of 400 mg of prednisone (or an equivalent potency of another steroid) for myeloma is not considered a regimen

• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

• Life expectancy > 3 months

• Platelet count ≥ 75 x 10^{9/L (≥ 50 x 10}9/L if bone marrow is extensively infiltrated)

• Absolute neutrophil count ≥ 1.5 x 10^{9/L (≥ 1.0 x 10}9/L if bone marrow is extensively infiltrated)

• Aspartate transaminase (AST) and Alanine transaminase (ALT) ≤ 2.5 times upper limit of normal (ULN)

• Serum bilirubin ≤ 1.5 times ULN

• Creatinine clearance ≥ 30 mL/min; creatinine > 10 mL/min and < 30 mL/min due to significant myelomatous involvement of the kidneys allowed with medical director approval

• Serum potassium ≥ lower limit of normal (LLN)

• Serum magnesium ≥ LLN

• Serum phosphorus ≥ LLN

• Prior localized radiotherapy

Exclusion criteria:

• Plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS syndrome)

• Plasma cell leukemia

• Pregnant or nursing females; fertile patients must use effective contraception

• Peripheral neuropathy > grade 2

• Impaired cardiac function or clinically significant cardiac disease (including congenital long QT syndrome, history or presence of sustained ventricular tachyarrhythmia; history of ventricular fibrillation or Torsade de Pointes; bradycardia, defined as heart rate (HR) < 50 beats per minute (bpm) [pacemaker allowed provided HR ≥ 50 bpm]; corrected QT interval > 450 msec on screening ECG; left ventricular ejection fraction below normal on screening ECHO or multigated acquisition (MUGA) scan; right bundle branch block with left anterior hemiblock (bifascicular block); myocardial infarction or unstable angina within the past 6 months; New York Heart Association class III-IV congestive heart failure; uncontrolled hypertension; history of labile hypertension; history of poor compliance with an antihypertensive regimen)

• Impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of panobinostat

• Prior malignancy within the past 5 years except basal cell or squamous cell carcinoma or carcinoma in situ of the cervix

• Other concurrent severe and/or uncontrolled medical or psychiatric conditions (e.g., uncontrolled diabetes or active or uncontrolled infection), including abnormal laboratory values that could cause unacceptable safety risks or compromise protocol compliance

• Known positivity for HIV or hepatitis B or C

• Severe hypercalcemia (i.e., serum calcium ≥ 14 mg/dL)

• Significant history of non-compliance to medical regimens or unwillingness or inability to comply with instructions given by the study staff

• Concurrent medication that risk prolonging the QT interval or inducing Torsades de Pointes

• Prior panobinostat

• Received chemotherapy, bortezomib, thalidomide, lenalidomide or arsenic trioxide within 3 wks of enrollment (with the exception of nitrosoureas within 6 wks of enrollment)

• Received corticosteroids (>10 mg/day prednisone or equivalent) within three weeks before enrollment.

• Received immunotherapy within < 8 weeks; antibody within < 4 weeks; or radiation therapy to > 30% of marrow-bearing bone within < 2 weeks prior to starting study treatment; or who have not yet recovered from side effects of such therapies.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Comprehensive Blood and Cancer Center	Bakersfield	California	United States	93309-0633
2	James R. Berenson MD, Incorporated	West Hollywood	California	United States	90069
3	Rocky Mountain Cancer Centers - Denver Midtown	Denver	Colorado	United States	80218
4	Center for Cancer and Blood Disorders	Bethesda	Maryland	United States	20817

Sponsors and Collaborators

• Oncotherapeutics
• Novartis

Investigators

• Principal Investigator: James R. Berenson, MD, Oncotherapeutics

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Oncotherapeutics
• ClinicalTrials.gov Identifier: NCT00743288
• Other Study ID Numbers: CDR0000612441; ONCOTHER-CLBH589BUS15T; LBH
• First Posted: Aug 28, 2008
• Last Update Posted: May 8, 2014
• Last Verified: Apr 1, 2014

• Keywords provided by Oncotherapeutics: stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma; refractory multiple myeloma
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Melphalan; Panobinostat

Study Results

Participant Flow

Recruitment Details	This is a multicenter study

Arm/Group Title	Melphalan and Panobinostat Schedule A	Melphalan and Panobinostat Schedule B1	Melphalan and Panobinostat Schedule B2	Melphalan and Panobinostat Schedule C	Melphalan and Panobinostat Schedule D1	Melphalan and Panobinostat Schedule D2	Melphalan and Panobinostat Schedule D3
Arm/Group Description	10mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1-4 of a 28-day cycle and melphalan PO at 0.05 mg/kg on days 1-5 of week 1.	10mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1-4 of a 28-day cycle and melphalan PO at 0.05 mg/kg on days 1, 3 and 5 of week 1.	20mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1-4 of a 28-day cycle and melphalan PO at 0.05 mg/kg on days 1, 3 and 5 of week 1.	20 mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1 and 2 of a 28-day cycle and melphalan PO at 0.05 mg/kg on days 1, 3 and 5 of week 1.	15 mg/daily of LBH589 PO and melphalan PO at 0.05 mg/kg on days 1, 3 and 5 of weeks 1 of a 28-day cycle	15 mg/daily of LBH589 PO and melphalan PO at 0.10 mg/kg on days 1, 3 and 5 of weeks 1 of a 28-day cycle	20 mg/daily of LBH589 PO and melphalan PO at 0.05 mg/kg on days 1, 3 and 5 of weeks 1 of a 28-day cycle
Period Title: Overall Study
STARTED	3	3	6	7	6	6	9
COMPLETED	0	0	1	0	0	1	0
NOT COMPLETED	3	3	5	7	6	5	9

Baseline Characteristics

Arm/Group Title	Melphalan and Panobinostat (LBH589)
Arm/Group Description	Schedule A: 10mg/daily of LBH589 per orem (PO) on days 1, 3 and 5 of weeks 1-4 of a 28-day cycle and melphalan PO at 0.05 mg/kg on days 1-5 of week 1. Toxicity led to the following changes in dose and schedule Schedule B1: 10mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1-4 and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1. Schedule B2: 20mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1-4 and 0.05 mg/kg melphalan POon days 1, 3 and 5 of week 1. Schedule C: 20mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1 and 2 and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1 Schedule D1: 15 mg/daily LBH589 PO and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1. Schedule D2: 15 mg/daily LBH589 PO and 0.10 mg/kg melphalan PO on days 1, 3 and 5 of week 1. Schedule D3: 20 mg/daily LBH589 PO and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1.
Overall Participants	40
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	65.4
Sex: Female, Male (Count of Participants)
Female	15 37.5%
Male	25 62.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	2 5%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	4 10%
White	32 80%
More than one race	0 0%
Unknown or Not Reported	2 5%
Region of Enrollment (participants) [Number]
United States	40 100%
Prior regimens (number of prior regimens) [Median (Full Range) ]
Number of prior regimens	4
Number of Bortezomib-containing prior regimens	2

Outcome Measures

1. Secondary Outcome

Title	Duration of Response
Time Frame	First evidence of PR or better (for overall response) and MR or better (for clinical benefit response) to start of disease progression or death

Outcome Measure Data

Analysis Population Description

Only three patients had responses.

Arm/Group Title	Melphalan and Panobinostat Schedule B
Arm/Group Description	B1: 10mg/daily LBH589 on days 1, 3 and 5 of weeks 1-4 and 0.05mg/kg melphalan on days 1, 3 and 5 of week 1. B2: 20mg/daily LBH589 on days 1, 3 and 5 of weeks 1-4 and 0.05mg/kg melphalan on days 1, 3 and 5 of week 1.
Measure Participants	3
Median (Full Range) [months]	8.1

2. Secondary Outcome

Title	Time to Progression
Time Frame	Time from the start of treatment to progressive disease

Outcome Measure Data

Analysis Population Description

All cohorts were analyzed

Arm/Group Title	Melphalan and Panobinostat
Arm/Group Description	Schedule A: 10mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1-4 of a 28-day cycle and melphalan PO at 0.05 mg/kg on days 1-5 of week 1. Toxicity led to the following changes in dose and schedule Schedule B1: 10mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1-4 and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1. Schedule B2: 20mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1-4 and 0.05 mg/kg melphalan POon days 1, 3 and 5 of week 1. Schedule C: 20mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1 and 2 and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1 Schedule D1: 15 mg/daily LBH589 PO and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1. Schedule D2: 15 mg/daily LBH589 PO and 0.10 mg/kg melphalan PO on days 1, 3 and 5 of week 1. Schedule D3: 20 mg/daily LBH589 PO and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1.
Measure Participants	40
Median (Full Range) [months]	1.6

3. Primary Outcome

Title	Maximum Tolerated Dose (MTD)
Description	Phase 1: to determine the MTD of panobinostat (LBH589) in combination with melphalan to be used in the Phase 2 portion of the study
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

MTD for Melphalan and Panobinostat was reached in the cohort of 6 participants who received 20 mg/daily LBH589 PO and melphalan PO at 0.05 mg/kg on days 1, 3 and 5 of week 1 of each cycle. Three additional patients were enrolled as part of the phase 2 expansion.

Arm/Group Title	Melphalan and Panobinostat Schedule D3
Arm/Group Description	20mg daily LBH589 and 0.05mg/kg melphalan on days 1, 3 and 5 of week 1
Measure Participants	6
Number [mg LBH589]	20

4. Primary Outcome

Title	MTD
Description	Phase 1: to determine MTD of melphalan in combination with panobinostat to be used in the Phase 2 portion of the study
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Melphalan and Panobinostat Schedule D3
Arm/Group Description	20mg daily LBH589 and 0.05mg/kg melphalan on days 1, 3 and 5 of week 1
Measure Participants	6
Number [mg/kg melphalan]	0.05

5. Primary Outcome

Title	Overall Response Rate (ORR) and Clinical Benefit Rate (CBR) [ORR= Complete Response (CR) + Very Good Partial Response (VGPR) + Partial Response (PR)]; CBR=ORR + Minimal Response (MR)] Following Treatment With Panobinostat and Melphalan
Description	Responses were evaluated according to criteria modified from those developed by Blade et al., 1998 The reference point for evaluating response improvement is the baseline. This baseline reference point is also valid when a patient has already achieved a response and transitions through into a better response grade.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Melphalan and Panobinostat Schedule A	Melphalan and Panobinostat Schedule B	Melphalan and Panobinostat Schedule C	Melphalan and Panobinostat Schedule D	Melphalan and Panobinostat All Patients
Arm/Group Description	10mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1-4 of a 28-day cycle and melphalan PO at 0.05 mg/kg on days 1-5 of week 1.	Schedules B1 and B2 B1: 10 mg/daily LBH589 on days 1, 3 and 5 of weeks 1-4 of a 28 day schedule and 0.04 mg/kg melphalan on days 1, 3 and 5 of week 1. B2:20 mg/daily LBH589 on days 1, 3 and 5 of weeks 1-4 of a 28 day schedule and 0.04 mg/kg melphalan on days 1, 3 and 5 of week 1	0.05 mg/kg melphalan on days 1, 3 and 5 of week 1 and 20 mg of LBH589 on days 1, 3, and 5 of weeks 1 and 2.	Schedules D1, D2 and D3 D1:LBH589 15mg/daily and melphalan 0.05mg/kg on days 1, 3 and 5 of week 1 D2: LBH589 15mg and daily melphalan 0.10 mg/kg on days 1, 3 and 5 of week 1 D3: LBH589 20mg daily and melphalan 0.05mg/kg on days days 1, 3 and 5 of week 1	Data for all patients irrespective of dosage
Measure Participants	3	9	7	21	40
CR	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
VGPR	0 0%	2 NaN	0 NaN	0 NaN	2 NaN
PR	0 0%	1 NaN	0 NaN	0 NaN	1 NaN
MR	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
SD (stable disease)	1 2.5%	5 NaN	5 NaN	12 NaN	23 NaN
Progressive disease (PD)	2 5%	1 NaN	2 NaN	9 NaN	14 NaN
ORR (CR+VGPR+ PR)	0 0%	3 NaN	0 NaN	0 NaN	3 NaN
CBR (ORR+MR)	0 0%	3 NaN	0 NaN	0 NaN	3 NaN

Adverse Events

Time Frame	24 months
Arm/Group Title	Melphalan and Panobinostat
Arm/Group Description	Schedule A: 10mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1-4 of a 28-day cycle and melphalan PO at 0.05 mg/kg on days 1-5 of week 1. Toxicity led to the following changes in dose and schedule Schedule B1: 10mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1-4 and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1. Schedule B2: 20mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1-4 and 0.05 mg/kg melphalan POon days 1, 3 and 5 of week 1. Schedule C: 20mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1 and 2 and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1 Schedule D1: 15 mg/daily LBH589 PO and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1. Schedule D2: 15 mg/daily LBH589 PO and 0.10 mg/kg melphalan PO on days 1, 3 and 5 of week 1. Schedule D3: 20 mg/daily LBH589 PO and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1.
All Cause Mortality
	Melphalan and Panobinostat
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Melphalan and Panobinostat
	Affected / at Risk (%)	# Events
Total	7/40 (17.5%)
Infections and infestations
Sepsis	1/40 (2.5%)	1
Gram-negative sepsis	1/40 (2.5%)	1
Injury, poisoning and procedural complications
Vertebral compression fracture	1/40 (2.5%)	1
Metabolism and nutrition disorders
Hypecalcemia	1/40 (2.5%)	1
Hyponatremia	1/40 (2.5%)	1
Psychiatric disorders
Altered mental status	1/40 (2.5%)	1
Respiratory, thoracic and mediastinal disorders
Pneumonia	1/40 (2.5%)	1
Vascular disorders
Deep vein thrombosis with oulmonary embolism	1/40 (2.5%)	1
Other (Not Including Serious) Adverse Events
	Melphalan and Panobinostat
	Affected / at Risk (%)	# Events
Total	22/40 (55%)
Blood and lymphatic system disorders
Anemia (>=grade 3)	6/40 (15%)	6
Leukopenia	6/40 (15%)	6
Lymphopenia	9/40 (22.5%)	9
Neutropenia	11/40 (27.5%)	11
Thrombocytopenia	10/40 (25%)	10
Metabolism and nutrition disorders
Hyponatremia	2/40 (5%)	2

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.