T-Cell Replete Haploidentical Donor Hematopoietic Stem Cell Plus Natural Killer (NK) Cell Transplantation in Patients With Hematologic Malignancies Relapsed or Refractory Despite Previous Allogeneic Transplant

• Sponsor: St. Jude Children's Research Hospital (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01621477
• Collaborator: Assisi Foundation (Other)
• Enrollment: 34
• Location: 1
• Arm: 1
• Duration (Months): 40
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

The primary aim of this protocol is to evaluate if the one-year survival is significantly improved in the group of patients who receive a T-cell replete haploidentical donor hematopoietic cell transplant (HCT) with a novel reduced intensity conditioning regimen. Study population will consist of patients (21 years or under) with hematologic malignancies that have relapsed or are refractory after prior allogeneic transplant. Toxicity will be evaluated by the rate of transplant related mortality and the rates of moderate and severe graft-versus-host disease (GvHD) at day 100. The investigators will describe event-free, and disease-free survival at one year, as well as the rates of hematopoietic recovery and donor engraftment and study comprehensively immune reconstitution following T-cell replete haploidentical transplantation.

Condition or Disease	Intervention/Treatment	Phase
Acute Lymphoblastic Leukemia; Acute Myelocytic Leukemia; Chronic Myelocytic Leukemia; Juvenile Myelomonocytic Leukemia; Myelodysplastic Syndrome; Hodgkin or Non-Hodgkin Lymphoma; Sarcoma, Myeloid	Drug: clofarabine; Drug: cytarabine; Drug: busulfan; Drug: Plerixafor; Drug: cyclophosphamide; Drug: antithymocyte globulin (rabbit); Biological: stem cells; Drug: Tacrolimus; Drug: mycophenolate mofetil	Phase 2

Detailed Description

Patients with refractory hematologic malignancies, including those who develop recurrent disease after allogeneic hematopoietic cell transplantation, have a dismal prognosis. Historically, both regimen-related mortality and disease recurrence have been significant causes of treatment failure in this heavily pre-treated patient population. Our institution has utilized mismatched family member (haploidentical) donors for these patients for a number of years for the following reasons: (1) Only 30% of patients have matched related donors available; (2) transplantation can be performed more rapidly since the time to unrelated donor transplantation averages 3 to 4 months; (3) no other curative treatment options are available. These therapeutic interventions have been largely successful given the dismal prognosis in this patient group; however disease recurrence remains the most significant cause of treatment failure. To provide maximum benefit for this challenging population, the goals of a therapeutic transplant protocol should include: (1) a conditioning regimen that is well tolerated, even in a heavily pre-treated population; but it should also provide substantial antileukemia effects, and (2) should establish rapid immune recovery such that the patient may benefit from graft versus leukemia effect and early protection from life threatening infections while also limiting dangerous and counter-productive graft versus host disease.

The primary aim of this protocol will be to evaluate if the one-year survival is significantly improved in the group of patients receiving T-cell replete haploidentical donor HCT with a novel clofarabine, cytarabine, busulfan, plerixafor, cyclophosphamide, and ATG based reduced intensity conditioning regimen whose hematologic malignancy has relapsed or is refractory after prior allogeneic transplant. Toxicity will be evaluated by the rate of transplant related mortality and the rates of moderate and severe graft versus host disease at day 100. The investigators will also describe event-free, and disease-free survival at one year, as well as the rates of hematopoietic recovery and donor engraftment. Additionally, the investigators will study comprehensively immune reconstitution following T-cell replete haploidentical transplantation.

PRIMARY OBJECTIVE:

• Evaluate if the one-year survival is significantly improved in a group of children receiving a therapeutic regimen for high-risk hematologic malignancy that is relapsed or refractory despite previous allogeneic hematopoietic cell transplantation (HCT) using a novel reduced intensity conditioning and T-cell replete haploidentical donor hematopoietic stem cell plus NK cell transplantation.

SECONDARY OBJECTIVES:

• Estimate the incidence of malignant relapse, event-free survival, and disease free survival (DFS) at one-year post-transplantation.

• Estimate incidence and severity of acute and chronic (GVHD).

• Estimate the rate of transplant related mortality (TRM) in the first 100 days after transplantation.

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: T-Cell Replete Haploidentical Donor Hematopoietic Stem Cell Plus Natural Killer (NK) Cell Transplantation in Patients With Hematologic Malignancies Relapsed or Refractory Despite Previous Allogeneic Transplant
• Study Start Date: Aug 1, 2012
• Actual Primary Completion Date: Dec 1, 2015
• Actual Study Completion Date: Dec 1, 2015

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment All study participants. Interventions: clofarabine, cytarabine, busulfan, plerixafor, cyclophosphamide, antithymocyte globulin (rabbit), stem cells, tacrolimus, mycophenolate mofetil

Drug: clofarabine; Given on Day -9 and Day -8 (Day 0 is first stem cell infusion). Drug class: antineoplastic agent; Other Names: Cl-F-Ara-A CAFdA Clofarex Clolar(TM) ; Drug: cytarabine; Given on Day -9 and Day -8 (Day 0 is first stem cell infusion). Drug class: antineoplastic agent; Other Names: Ara-C ; Drug: busulfan; Given on Day -7 and Day -6 (Day 0 is first stem cell infusion). Drug class: antineoplastic agent; Other Names: Myleran(R) Busulfex ; Drug: Plerixafor; Given on Day -7 and Day -6 (Day 0 is first stem cell infusion). Drug class: Hematopoietic Stem Cell Mobilizer; Other Names: AMD3100 Mozobil(R) ; Drug: cyclophosphamide; Given on Day -5 and Day +4 (Day 0 is first stem cell infusion). Drug class: antineoplastic agent; immunosuppressive agent.; Other Names: Cytoxan ; Drug: antithymocyte globulin (rabbit); Given on Day -4, Day -3, Day -2, and Day -1 (Day 0 is first stem cell infusion). Drug class: immunosuppressive agent.; Other Names: Rabbit ATG Rabbit Thymoglobulin(R) ; Biological: stem cells; Patients undergo T cell replete Hematopoietic stem cell infusion on Day 0 and Day +1. Patients undergo natural killer (NK) cell transplantation on day +6 (Day 0 is first stem cell infusion).; Other Names: HSC infusion ; Drug: Tacrolimus; Given on Day +11 (Day 0 is first stem cell infusion). Drug class: immunosuppressive agent.; Other Names: FK506 Prograf(R) Protonic(R) ; Drug: mycophenolate mofetil; Given on Day +11 (Day 0 is first stem cell infusion). Drug class: immunosuppressive agent.; Other Names: MMF CellCept(R)

Outcome Measures

Primary Outcome Measures

1. One-year Survival (OS) [One year post transplant]

   Evaluate the number of participants alive at 1 year. The number of participants surviving to one-year post-transplantation is given.

Secondary Outcome Measures

1. Incidence of Malignant Relapse [One year post transplantation.]

   Estimate the incidence of malignant relapse at one year post-transplant. The number of participants with malignant relapse or progressive disease is given. Relapse was evaluated using standard WHO criteria for each disease.

2. Event-Free Survival (EFS) [one year post transplant]

   Estimate the EFS at one-year post-transplantation. The event is defined as relapse or death due to any cause. The number of participants who were alive without relapse at one year post-transplant is reported.

3. Disease-Free Survival (DFS) [one year post transplant]

   Estimate the DFS at one-year post-transplantation. The event is defined as relapse or death due to relapse. The number of participants who did not relapse up to one year post transplant is reported.

4. Incidence and Severity of Acute Graft Versus Host Disease (GVHD) [100 days post transplant]

   The number of participants with acute GVHD is given, organized by grade. Participants are graded on a scale from 1 to 4, with 1 being mild and 4 being severe.

5. Incidence and Severity of Chronic Graft Versus Host Disease (GVHD) [100 days post transplant]

   The severity of chronic GVHD will be described. Chronic GVHD was evaluated using NIH Consensus Global Severity Scoring. The number of participants with chronic GVHD is given, organized by severity.

6. Number of Participants With Transplant Related Mortality (TRM) [100 days post transplant]

   The number of participants who died due to TRM in the first 100 days post-transplant is given.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria - for transplant recipient:

• Age less than 21 years.

• One of the following hematologic malignancies that has relapsed or remains refractory after prior allogeneic HCT:

• Acute lymphoblastic leukemia (ALL)

• Acute myeloid leukemia (AML) (including myeloid sarcoma)

• Chronic myelogenous leukemia (CML), juvenile myelomonocytic leukemia (JMML), myelodysplastic syndrome (MDS), Hodgkin or non-Hodgkin lymphoma (NHL)

• Has a suitable single haplotype matched (≥ 3 of 6) family member donor.

• Does not have any other active malignancy other than the one for which this transplant is indicated.

• If prior central nervous system (CNS) leukemia, it must be treated and have no evidence of CNS disease

• Does not have current uncontrolled bacterial, fungal, or viral infection per the judgment of the principal investigator.

• Patient must fulfill pre-transplant evaluation:

• Left ventricular ejection fraction greater than 40%, or shortening fraction greater than or equal to 25%.

• Creatinine clearance or Glomerular Filtration Rate of ≥70 ml/min/1.73m^2.

• Forced vital capacity (FVC) ≥ 40% of predicted value; or pulse oximetry ≥ 92% on room air if patient is unable to perform pulmonary function testing.

• Karnofsky or Lansky (age-dependent) performance score ≥ 50.

• Total bilirubin ≤ 1.5 times the upper limit of normal for age.

• Alanine aminotransferase (ALT) ≤ 3 times the upper limit of normal for age.

• Not pregnant. If female with child bearing potential, must be confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment.

• Not breast feeding.

• Does not have active acute bronchiolitis obliterans or bronchiolitis obliterans organizing pneumonia.

Inclusion Criteria - for donor:

• At least single haplotype matched (≥ 3 of 6) family member,

• At least 18 years of age.

• Human immunodeficiency virus (HIV) negative.

• Not pregnant as confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment (if female).

• Not breast feeding.

• A suitable donor is identified as either:

• Has completed the process of donor eligibility determination as outlined in 21 CFR 1271 and agency guidance; OR

• Does not meet 21 CFR 1271 eligibility requirements, but has a declaration of urgent medical need completed by the principal investigator or physician sub-investigator per 21 CFR 1271.

Exclusion Criteria:

• Does not meet above inclusion criteria.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St. Jude Children's Research Hospital	Memphis	Tennessee	United States	38105

Sponsors and Collaborators

• St. Jude Children's Research Hospital
• Assisi Foundation

Investigators

• Principal Investigator: Brandon M. Triplett, MD, St. Jude Children's Research Hospital

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

Publications

None provided.

• Responsible Party: St. Jude Children's Research Hospital
• ClinicalTrials.gov Identifier: NCT01621477
• Other Study ID Numbers: HAP3R; NCI-2012-00554
• First Posted: Jun 18, 2012
• Last Update Posted: Feb 20, 2017
• Last Verified: Dec 1, 2016

• Keywords provided by St. Jude Children's Research Hospital: Hematologic malignancy; Hematopoietic cell transplant
• Additional relevant MeSH terms: Leukemia; Neoplasms; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Hematologic Neoplasms; Leukemia, Myelomonocytic, Juvenile; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Sarcoma, Myeloid; Myelodysplastic Syndromes; Cytarabine; Plerixafor; Mycophenolic Acid; Cyclophosphamide; Busulfan; Clofarabine; Tacrolimus; Thymoglobulin; Antilymphocyte Serum

Study Results

Participant Flow

Recruitment Details	Thirty four participants were enrolled at St. Jude Children's Research Hospital between August 2012 and November 2014.
Pre-assignment Detail	Of the 34 participants enrolled on the study, 17 were donors. Donors did not receive treatment and are not followed for data collection to answer the study objectives. They are therefore not included in the results reported here.

Arm/Group Title	Treatment
Arm/Group Description	Study participants (excluding donors) who were enrolled and underwent transplant.
Period Title: Overall Study
STARTED	17
COMPLETED	17
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment
Arm/Group Description	Study participants (excluding donors) who were enrolled and underwent transplant. Donors did not receive treatment and are not followed for data collection to answer the study objectives. They are therefore not included in the results reported here.
Overall Participants	17
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	8.84 (5.84)
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	6.97
Gender (Count of Participants)
Female	9 52.9%
Male	8 47.1%

Outcome Measures

1. Primary Outcome

Title	One-year Survival (OS)
Description	Evaluate the number of participants alive at 1 year. The number of participants surviving to one-year post-transplantation is given.
Time Frame	One year post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment
Arm/Group Description	Study participants (excluding donors) who were enrolled and underwent transplant.
Measure Participants	17
Number [participants]	7 41.2%

2. Secondary Outcome

Title	Incidence of Malignant Relapse
Description	Estimate the incidence of malignant relapse at one year post-transplant. The number of participants with malignant relapse or progressive disease is given. Relapse was evaluated using standard WHO criteria for each disease.
Time Frame	One year post transplantation.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment
Arm/Group Description	Study participants (excluding donors) who were enrolled and underwent transplant.
Measure Participants	17
Number [participants]	10 58.8%

3. Secondary Outcome

Title	Event-Free Survival (EFS)
Description	Estimate the EFS at one-year post-transplantation. The event is defined as relapse or death due to any cause. The number of participants who were alive without relapse at one year post-transplant is reported.
Time Frame	one year post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment
Arm/Group Description	Study participants (excluding donors) who were enrolled and underwent transplant.
Measure Participants	17
Number [participants]	4 23.5%

4. Secondary Outcome

Title	Disease-Free Survival (DFS)
Description	Estimate the DFS at one-year post-transplantation. The event is defined as relapse or death due to relapse. The number of participants who did not relapse up to one year post transplant is reported.
Time Frame	one year post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment
Arm/Group Description	Study participants (excluding donors) who were enrolled and underwent transplant.
Measure Participants	17
Number [participants]	7 41.2%

5. Secondary Outcome

Title	Incidence and Severity of Acute Graft Versus Host Disease (GVHD)
Description	The number of participants with acute GVHD is given, organized by grade. Participants are graded on a scale from 1 to 4, with 1 being mild and 4 being severe.
Time Frame	100 days post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment
Arm/Group Description	Study participants (excluding donors) who were enrolled and underwent transplant.
Measure Participants	17
No Acute GVHD	9 52.9%
Grade I	3 17.6%
Grade II	1 5.9%
Grade III	3 17.6%
Grade IV	1 5.9%

6. Secondary Outcome

Title	Incidence and Severity of Chronic Graft Versus Host Disease (GVHD)
Description	The severity of chronic GVHD will be described. Chronic GVHD was evaluated using NIH Consensus Global Severity Scoring. The number of participants with chronic GVHD is given, organized by severity.
Time Frame	100 days post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment
Arm/Group Description	Study participants (excluding donors) who were enrolled and underwent transplant.
Measure Participants	17
No Chronic GVHD	15 88.2%
Mild	0 0%
Moderate	2 11.8%
Severe	0 0%

7. Secondary Outcome

Title	Number of Participants With Transplant Related Mortality (TRM)
Description	The number of participants who died due to TRM in the first 100 days post-transplant is given.
Time Frame	100 days post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment
Arm/Group Description	Study participants (excluding donors) who were enrolled and underwent transplant.
Measure Participants	17
Number [participants]	2 11.8%

Adverse Events

Time Frame	Participants were followed for adverse events from the start of conditioning therapy and throughout the first year post hematopoietic cell transplant (HCT).
Arm/Group Title	Treatment
Arm/Group Description	Study participants (excluding donors) who were enrolled to receive treatment with clofarabine, cytarabine, busulfan, plerixafor, cyclophosphamide, antithymocyte globulin (rabbit), stem cells, tacrolimus, and mycophenolate mofetil. Donors did not receive treatment and are not followed for data collection to answer the study objectives. They are therefore not included in the results reported here.
All Cause Mortality
	Treatment
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment
	Affected / at Risk (%)	# Events
Total	10/17 (58.8%)
Blood and lymphatic system disorders
Graft failure	1/17 (5.9%)	1
Thrombotic microangiopathy (disorder)	1/17 (5.9%)	1
Hemorrhage, pulmonary	3/17 (17.6%)	3
Cardiac disorders
Hypotension	1/17 (5.9%)	1
Pericardial effusion	1/17 (5.9%)	1
Gastrointestinal disorders
Stomatitis, viral	1/17 (5.9%)	1
General disorders
Fever without neutropenia	5/17 (29.4%)	6
Acute infusion reaction, stem cells	2/17 (11.8%)	2
Engraftment syndrome	1/17 (5.9%)	1
Hepatobiliary disorders
Hepatitis	1/17 (5.9%)	1
Immune system disorders
Allergic reaction, dexmedetomidine (precedex)	1/17 (5.9%)	1
Infections and infestations
Febrile neutropenia	1/17 (5.9%)	1
Infection, enterobacter cloacae, blood	1/17 (5.9%)	1
Infection, pseudomonas aeruginosa, disseminated	1/17 (5.9%)	1
Infection, staphylococcus epidermidis, blood	1/17 (5.9%)	1
Pneumonia	1/17 (5.9%)	1
Nervous system disorders
Apnea	1/17 (5.9%)	1
Mood alteration	1/17 (5.9%)	1
Seizure	1/17 (5.9%)	1
Subdural hygroma	1/17 (5.9%)	1
Uremic encephalopathy (disorder)	1/17 (5.9%)	1
Renal and urinary disorders
Failure, renal	1/17 (5.9%)	1
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome (disorder	1/17 (5.9%)	1
Hypoxia	2/17 (11.8%)	2
Interstitial pneumonitis syndrome	1/17 (5.9%)	1
Nodule, pulmonary lobe of lung, right	1/17 (5.9%)	1
Respiratory failure (disorder)	1/17 (5.9%)	1
Tension pneumothorax, lung, right	1/17 (5.9%)	1
Other (Not Including Serious) Adverse Events
	Treatment
	Affected / at Risk (%)	# Events
Total	17/17 (100%)
Blood and lymphatic system disorders
Hemorrhagic cystitis	1/17 (5.9%)	1
Cardiac disorders
Bradycardia (finding)	1/17 (5.9%)	1
Cardiomyopathy	1/17 (5.9%)	1
Heart failure (disorder)	1/17 (5.9%)	1
Hypertension	6/17 (35.3%)	7
Hypotension	3/17 (17.6%)	4
Pericardial effusion	1/17 (5.9%)	1
Pulmonary hypertension	2/17 (11.8%)	2
Gastrointestinal disorders
Enteritis	1/17 (5.9%)	1
Ileus	1/17 (5.9%)	1
Mucositis	1/17 (5.9%)	1
Pneumatosis intestinalis	1/17 (5.9%)	1
General disorders
Fever without neutropenia	4/17 (23.5%)	4
Pain, knee, bilateral	1/17 (5.9%)	1
Pain, shoulder, bilateral	1/17 (5.9%)	1
Acute infusion reaction, NK cells	1/17 (5.9%)	1
Acute infusion reaction, stem cells	14/17 (82.4%)	16
Engraftment syndrome	5/17 (29.4%)	5
Hepatobiliary disorders
Cholecystitis	1/17 (5.9%)	1
Cholelithiasis	1/17 (5.9%)	1
Colitis	1/17 (5.9%)	1
Veno-occlusive disease, hepatic	2/17 (11.8%)	2
Immune system disorders
Allergic drug reaction, cefepime	1/17 (5.9%)	1
Allergic drug reaction, vancomycin	2/17 (11.8%)	2
Cytokine release syndrome, ATG	12/17 (70.6%)	12
Infections and infestations
Candidiasis, oral	1/17 (5.9%)	1
Encephalitis	1/17 (5.9%)	1
Febrile neutropeenia	15/17 (88.2%)	25
Hepatitis	1/17 (5.9%)	1
Infection, adenovirus, respiratory tract	1/17 (5.9%)	1
Infection, adenovirus, stool	10/17 (58.8%)	12
Infection, BK virus, blood	5/17 (29.4%)	5
Infection, BK virus, urine	4/17 (23.5%)	4
Infection, candida parapsilosis, blood	1/17 (5.9%)	1
Infection, coagulase negative staphylococcus, blood	1/17 (5.9%)	1
Infection, enterococcus faecalis, blood	1/17 (5.9%)	1
Infection, Epstein Barr virus, blood	2/17 (11.8%)	2
Infection, human herpes virus 6, blood	5/17 (29.4%)	6
Infection, klebsiella, blood	1/17 (5.9%)	1
Infection, lactobacillus, urinary tract	1/17 (5.9%)	1
Infection, microbacterium aurum, blood	1/17 (5.9%)	1
Infection, parainfluenza type 4, respiratory tract	1/17 (5.9%)	1
Infection, respiratory syncytial virus, respiratory tract	1/17 (5.9%)	1
Infection, rotavirus, stool	1/17 (5.9%)	2
Infection, staphylococcus epidermidis, blood	1/17 (5.9%)	1
Infection, staphylococcus, urine	1/17 (5.9%)	1
Infection, vancomycin resistant enterococcus faecium, stool	1/17 (5.9%)	1
Infection, vancomycin-resistant enterococcus, blood	2/17 (11.8%)	3
Infection, vancomycin resistant enterococcus, rectum	1/17 (5.9%)	1
Pneumonia	1/17 (5.9%)	1
Reactivation, Epstein Barr virus	1/17 (5.9%)	1
Sinusitis	2/17 (11.8%)	2
Metabolism and nutrition disorders
Hemophagocytic lymphohistiocytosis (disorder)	1/17 (5.9%)	1
Hypocalcemia (disorder)	1/17 (5.9%)	1
Nervous system disorders
Encephalopathy	1/17 (5.9%)	1
Obstructive sleep apnea	1/17 (5.9%)	1
Seizure	1/17 (5.9%)	1
Sensory neuropathy	1/17 (5.9%)	1
Renal and urinary disorders
Cystitis	1/17 (5.9%)	1
Hemorrhagic cystitis	5/17 (29.4%)	5
Respiratory, thoracic and mediastinal disorders
Hypoxia	3/17 (17.6%)	3
Pleural effusion, bilateral	2/17 (11.8%)	2
Pleural effusion, right	1/17 (5.9%)	1
Skin and subcutaneous tissue disorders
Neutrophilic dermatosis	1/17 (5.9%)	1
Vascular disorders
Occlusive thrombus (morphologic abnormality)	1/17 (5.9%)	1
Thrombus, upper extremity and neck, left	1/17 (5.9%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.