Selective Depletion of CD45RA+T Cells From Allogeneic Peripheral Blood Stem Cell Grafts for the Prevention of GVHD

• Sponsor: Fred Hutchinson Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00914940
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 41
• Locations: 2
• Arm: 1
• Actual Duration (Months): 125.3
• Patients Per Site: 20.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

RATIONALE: Allogeneic hematopoietic stem cell transplant (HSCT) is a treatment that can cure acute leukemia and myelodysplasia. After giving the patient chemotherapy and total body irradiation to stop the growth of cancer and remove the patient's diseased bone marrow, healthy stem cells from a donor are infused into the patient to replace the patient's bone marrow and make red and white blood cells and platelets. Unfortunately HSCT is often complicated by 'graft versus host disease' (GVHD) in which the transplanted cells from a donor can make an immune response against the body's normal cells and cause tissue damage and severe symptoms. Removing a subset of the donor T cells, called 'naive T cells', before transplant may reduce the frequency and intensity of GVHD.

PURPOSE: This phase II trial will determine whether the removal of the naive T cells from donor cells can decrease the rate and severity of graft-vs-host disease while preserving specific immunity against infections in patients with acute leukemia or advanced myelodysplastic syndromes.

Condition or Disease	Intervention/Treatment	Phase
Graft Versus Host Disease; Leukemia; Myelodysplastic Syndromes	Drug: Fludarabine Phosphate; Drug: Tacrolimus; Drug: Thiotepa; Radiation: Total-Body Irradiation (TBI); Other: Magnetic Affinity Cell Sorting; Procedure: Peripheral Blood Stem Cell Transplantation; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Biological: T Cell-Depleted Hematopoietic Stem Cell Transplantation	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Estimate the probability of grades II-IV acute graft-vs-host disease (GVHD) in patients with acute leukemia or advanced myelodysplastic syndromes treated with CD45RA+ T-cell-depleted allogeneic peripheral blood stem cell transplantation and compare this to relevant historical experience.

• Estimate the probability of graft failure in these patients.

Secondary

• Evaluate immune reconstitution and pathogen-specific T-cell reconstitution in these patients.

• Estimate the probability of transplant-related mortality by day 100 in these patients.

• Estimate the probability of relapse in these patients.

• Estimate the probability and severity of chronic GVHD in these patients.

OUTLINE: This is a multicenter study.

• Myeloablative conditioning regimen: Patients undergo total body irradiation twice daily for 4 days (Days -10 to -7) Patients also receive thiotepa IV over 4 hours for 2 days (Days -6 and -5) and fludarabine phosphate IV over 30 minutes for 5 days (Days -6 to -2.)

• Transplantation: Patients receive a CD34+ enriched allogeneic peripheral blood stem cell (PBSC) product followed by a CD45RA+ T-cell-depleted allogeneic PBSC product on day 0.

• Graft-vs-host disease (GVHD) prophylaxis: Patients will receive Tacrolimus as per cohort

1. If the rate of grade II-IV acute GVHD in the first 35 patients is significantly reduced (compared to historical controls), subsequent patients are enrolled in cohort 2.

• Cohort 1: Patients receive tacrolimus IV continuously or orally twice daily beginning on day -1 and continuing until day 50, followed by a standard taper in the absence of grade II-IV acute GVHD.

• Cohort 2: Patients receive tacrolimus IV continuously or orally twice daily beginning on day -1 and continuing until day 30, followed by a rapid taper in the absence of grade II-IV acute GVHD.

Patients are followed actively for at least 1 year post transplant.

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multi-center Phase II Study of Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts for the Prevention of GVHD
• Actual Study Start Date: Dec 17, 2009
• Actual Primary Completion Date: Dec 1, 2019
• Actual Study Completion Date: May 26, 2020

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Arm 1 CONDITIONING: Patients undergo total-body irradiation twice daily on days -10 to -7. Patients also receive thiotepa IV over 4 hours on days -6 and -5 and fludarabine IV over 30 minutes on days -6 to -2. TRANSPLANTATION: Patients undergo infusion of CD34+ enriched allogeneic peripheral blood stem cells (PBSC) followed by CD45RA+ T-cell-depleted allogeneic PBSC on day 0. GRAFT-VS-HOST DISEASE PROPHYLAXIS: Cohort A: Patients receive tacrolimus IV continuously or orally twice daily beginning on day -1 and continuing until day 50 followed by standard taper in the absence of grade II-IV acute GVHD. Cohort B: Patients receive tacrolimus IV continuously or orally twice daily beginning on day -1 and continuing until day 30 followed by rapid taper in the absence of grade II-IV acute GVHD.

Drug: Fludarabine Phosphate; Fludarabine will be administered in a dose of 25 mg/m2/day IV over approximately 30 minutes for 5 consecutive days (day -6 to -2). The total dose of fludarabine will be 125 mg/m2.; Other Names: 2-F-ara-AMP Beneflur Fludara ; Drug: Tacrolimus; Tacrolimus will be administered beginning on day -1 at a dose of 0.03 mg/kg/day by continuous IV infusion. For the first cohort of 35 patients, if there is no evidence of grade II-IV acute GVHD on or prior to day 50, tacrolimus should then be tapered at the rate of approximately 5% of the day 50 dose each week for liquid, and 20% of the day 50 dose per month for capsules. In the second cohort of 25 patients if there is no evidence of grade II GVHD on or prior to day 30, tacrolimus should then be tapered at the rate of approximately 8% of the day 30 dose each week for liquid, and 33% of the day 30 dose per month for capsules.; Other Names: Advagraf FK 506 Prograf Protopic ; Drug: Thiotepa; Thiotepa will be administered in a dose of 5 mg/kg/day (adjusted body weight) IV over approximately 4 hours for 2 consecutive days (day -6 and day -5).; Other Names: Oncotiotepa STEPA TESPA Tespamin Tespamine TSPA ; Radiation: Total-Body Irradiation (TBI); TBI will be given as 165 cGy fractions twice per day x 4 days - total dose 1320cGy (days -10 to -7).; Other Names: TBI ; Other: Magnetic Affinity Cell Sorting; Device; Other Names: Magnetic-Activated Cell Sorter (CliniMACS, Miltenyi) ; Procedure: Peripheral Blood Stem Cell Transplantation; Patient will undergo a PBSC transplantation; Other Names: PBPC transplantation PBSC transplantation Peripheral Blood Progenitor Cell Transplantation Transplantation Peripheral Blood Stem Cell ; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Patients who are considered appropriate candidates for allogeneic hematopoietic stem cell transplantation; Biological: T Cell-Depleted Hematopoietic Stem Cell Transplantation; Patients who are eligible will receive a T Cell-Depleted Hematopoietic Stem Cell Transplantation

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Acute Graft-vs-host Disease (GVHD): Grade I-IV, Including Those With no Reportable Acute GVHD [Within 360 days of transplant]

   Number of participants with aGVHD and severity of aGVHD within the first 360 days post-transplant as graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. Acute GVHD is graded by standard criteria, and all suspected cases of acute GVHD will be confirmed histologically by biopsy of an affected organ. The severity of acute GVHD is determined by an assessment of the degree of involvement of the skin, liver, and gastrointestinal tract. Grade I is characterized as mild disease, Grade II as moderate, Grade III as severe (involvement of any organ system), and Grade IV as life-threatening.

2. Number of Participants Who Did Not Engraft After Receiving a CD45RA+ T Cell Depleted PBSC Transplant [Up to 5 years post transplant]

   Graft failure is defined as either a failure to reach an ANC of >500/uL for 3 consecutive days by day 28 post-transplant, or an irreversible decrease in ANC <100 after an established donor graft, unless there is a reasonable explanation such as a viral infection or drug effect that may be responsible for a reversible decrease in ANC.

Secondary Outcome Measures

1. Transplant-related Mortality by Day 100 [Transplant to day 100]

   Number of participants who died due to transplant-related issues within the first 100 days of transplant

2. Number of Participants Who Have Relapsed Within 5 Years of CD45RA+ T Cell Depleted PBSC Transplant [Up to 5 years post transplant]

   Relapse is defined by the presence of malignant cells in marrow, peripheral blood, or extramedullary sites by histopathology. Testing for recurrent malignancy in the blood and bone marrow performed by monitoring the CBC and bone marrow at Day 28, 58, 80, 360, and as needed for suspected relapse.

3. Number of Participants With Chronic GVHD [Up to 5 years post transplant]

   Chronic GVHD measured by meeting NIH criteria and treated with immune suppression

Eligibility Criteria

Criteria

• Ages Eligible for Study: 14 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following:

• Acute lymphocytic leukemia (ALL) or acute myeloid leukemia (AML) in first or subsequent remission

• ALL or AML in relapse or primary refractory ALL or AML with a circulating blast count ≤ 10,000/mm^3

• Refractory anemia with excess blasts (RAEB) (RAEB-1 or RAEB-2) if the patient has received induction chemotherapy within the past 60 days

• Appropriate candidate for allogeneic hematopoietic stem cell transplantation (HSCT)

• No CNS involvement refractory to intrathecal chemotherapy and/or standard cranial-spinal radiotherapy

PATIENT CHARACTERISTICS:

• Age 14-55

• Creatinine < 1.5 mg/dL

• Cardiac ejection fraction > 45%

• DLCO corrected > 60% of predicted

• Total bilirubin < 2 times upper limit of normal (ULN) (unless attributed to Gilbert syndrome)

• AST and ALT < 2 times ULN

• Not pregnant or nursing

• Fertile patients must use effective contraception during and for 12 months after transplantation

• HIV negative

• No co-existing disease (other than leukemia or RAEB) that would limit life expectancy to < 3 months

• No uncontrolled infection that, in the opinion of the consulting infectious disease physician, would contraindicate myeloablative HSCT

• No other medical condition that would contraindicate HSCT

• No known hypersensitivity to tacrolimus

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior HSCT

• No concurrent participation in other experimental studies for the prevention of graft-vs-host disease

DONOR CHARACTERISTICS:

• Genotypic or phenotypic HLA-identical related donor

• Able to donate peripheral blood stem cells

• Age > 14 years

• Applicable to male patients only: No female donors who have previously given birth to a male child or have had a pregnancy beyond the first trimester miscarriage or termination of pregnancy or nursing

• No donors who have received blood transfusions

• No CD45 Mutation with aberrant CD45RA isoform expression

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale University School of Medicine/Yale New Haven Hospital	New Haven	Connecticut	United States	06520
2	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109-1024

Sponsors and Collaborators

• Fred Hutchinson Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Marie Bleakley, MD, Fred Hutchinson Cancer Center
• Principal Investigator: Warren Shlomchik, MD, Yale University School of Medicine/Yale New Haven Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 28, 2018

More Information

Publications

None provided.

• Responsible Party: Fred Hutchinson Cancer Center
• ClinicalTrials.gov Identifier: NCT00914940
• Other Study ID Numbers: 2222.00; P30CA015704; P01CA018029; IR-6907; CDR0000644201; 0903004832; NCI-2010-00713; RG2810004
• First Posted: Jun 5, 2009
• Last Update Posted: Aug 20, 2020
• Last Verified: Jul 1, 2020

• Keywords provided by Fred Hutchinson Cancer Center: graft versus host disease; adult acute lymphoblastic leukemia in remission; recurrent adult acute lymphoblastic leukemia; childhood acute lymphoblastic leukemia in remission; recurrent childhood acute lymphoblastic leukemia; adult acute myeloid leukemia in remission; recurrent adult acute myeloid leukemia; adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(15;17)(q22;q12); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22); childhood acute myeloid leukemia in remission; recurrent childhood acute myeloid leukemia; childhood myelodysplastic syndromes; previously treated myelodysplastic syndromes; refractory anemia with excess blasts; de novo myelodysplastic syndromes; secondary myelodysplastic syndromes
• Additional relevant MeSH terms: Leukemia; Preleukemia; Myelodysplastic Syndromes; Graft vs Host Disease; Syndrome; Fludarabine; Fludarabine phosphate; Thiotepa; Tacrolimus

Study Results

Participant Flow

Recruitment Details	Participants were recruited based on physician referral at 2 academic medical centers between Dec 2009 and Oct 2014. The first patient was enrolled on December 17, 2009 and the last participant was enrolled in October 2014

Arm/Group Title	Overall Study Participants
Arm/Group Description	CD34+ enriched allogeneic peripheral blood stem cells (PBSC) followed by CD45RA+ T-cell-depleted allogeneic PBSC and tacrolimus for GVHD prophylaxis
Period Title: D0 to D100 Post-transplant
STARTED	41
COMPLETED	39
NOT COMPLETED	2
Period Title: D0 to D100 Post-transplant
STARTED	39
COMPLETED	31
NOT COMPLETED	8
Period Title: D0 to D100 Post-transplant
STARTED	31
COMPLETED	28
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Overall Study Participants
Arm/Group Description	CONDITIONING: Patients receive TBI twice per day on days -10 to -7, then thiotepa IV administered over approximately 4 hours on days -6 and -5, and fludarabine IV administered over 30 minutes on days -6 to -2. DONOR BONE MARROW TRANSPLANTATION: GCSF-mobilized CD34 enriched PBSC and CD45RA depleted cells infused on day 0. POST-TRANSPLANT IMMUNOSUPPRESSION: Ptients receive tacrolimus beginning on day -1 by continuous IV infusion, converting to oral formulation when oral feeding is established. If there is no evidence of grade II-IV acute GVHD prior to day 50, tacrolimus is then tapered.
Overall Participants	41
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	41 100%
>=65 years	0 0%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	37.7
Sex: Female, Male (Count of Participants)
Female	23 56.1%
Male	18 43.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 12.2%
Not Hispanic or Latino	35 85.4%
Unknown or Not Reported	1 2.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	3 7.3%
Asian	3 7.3%
Native Hawaiian or Other Pacific Islander	3 7.3%
Black or African American	0 0%
White	30 73.2%
More than one race	0 0%
Unknown or Not Reported	2 4.9%
Region of Enrollment (participants) [Number]
United States	41 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Acute Graft-vs-host Disease (GVHD): Grade I-IV, Including Those With no Reportable Acute GVHD
Description	Number of participants with aGVHD and severity of aGVHD within the first 360 days post-transplant as graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. Acute GVHD is graded by standard criteria, and all suspected cases of acute GVHD will be confirmed histologically by biopsy of an affected organ. The severity of acute GVHD is determined by an assessment of the degree of involvement of the skin, liver, and gastrointestinal tract. Grade I is characterized as mild disease, Grade II as moderate, Grade III as severe (involvement of any organ system), and Grade IV as life-threatening.
Time Frame	Within 360 days of transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Overall Study Participants
Arm/Group Description	CD34+ enriched allogeneic peripheral blood stem cells (PBSC) followed by CD45RA+ T-cell-depleted allogeneic PBSC and tacrolimus for GVHD prophylaxis
Measure Participants	41
No acute GVHD	11 26.8%
Grade I acute GVHD	2 4.9%
Grade II acute GVHD	25 61%
Grade III acute GVHD	3 7.3%
Grade IV acute GVHD	0 0%
Steroid refractory acute GVHD	0 0%

2. Primary Outcome

Title	Number of Participants Who Did Not Engraft After Receiving a CD45RA+ T Cell Depleted PBSC Transplant
Description	Graft failure is defined as either a failure to reach an ANC of >500/uL for 3 consecutive days by day 28 post-transplant, or an irreversible decrease in ANC <100 after an established donor graft, unless there is a reasonable explanation such as a viral infection or drug effect that may be responsible for a reversible decrease in ANC.
Time Frame	Up to 5 years post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Overall Study Participants
Arm/Group Description	CD34+ enriched allogeneic peripheral blood stem cells (PBSC) followed by CD45RA+ T-cell-depleted allogeneic PBSC and tacrolimus for GVHD prophylaxis
Measure Participants	41
Count of Participants [Participants]	0 0%

3. Secondary Outcome

Title	Transplant-related Mortality by Day 100
Description	Number of participants who died due to transplant-related issues within the first 100 days of transplant
Time Frame	Transplant to day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Overall Study Participants
Arm/Group Description	CD34+ enriched allogeneic peripheral blood stem cells (PBSC) followed by CD45RA+ T-cell-depleted allogeneic PBSC and tacrolimus for GVHD prophylaxis
Measure Participants	41
Count of Participants [Participants]	2 4.9%

4. Secondary Outcome

Title	Number of Participants Who Have Relapsed Within 5 Years of CD45RA+ T Cell Depleted PBSC Transplant
Description	Relapse is defined by the presence of malignant cells in marrow, peripheral blood, or extramedullary sites by histopathology. Testing for recurrent malignancy in the blood and bone marrow performed by monitoring the CBC and bone marrow at Day 28, 58, 80, 360, and as needed for suspected relapse.
Time Frame	Up to 5 years post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Overall Study Participants
Arm/Group Description	CD34+ enriched allogeneic peripheral blood stem cells (PBSC) followed by CD45RA+ T-cell-depleted allogeneic PBSC and tacrolimus for GVHD prophylaxis
Measure Participants	41
Count of Participants [Participants]	10 24.4%

5. Secondary Outcome

Title	Number of Participants With Chronic GVHD
Description	Chronic GVHD measured by meeting NIH criteria and treated with immune suppression
Time Frame	Up to 5 years post transplant

Outcome Measure Data

Analysis Population Description

Participants alive and without relapse at D100

Arm/Group Title	Overall Study Participants
Arm/Group Description	CD34+ enriched allogeneic peripheral blood stem cells (PBSC) followed by CD45RA+ T-cell-depleted allogeneic PBSC and tacrolimus for GVHD prophylaxis
Measure Participants	38
Chronic GVHD that meets NIH criteria	3 7.3%
No documented chronic GVHD	35 85.4%

Adverse Events

Time Frame	AEs and SAEs: Conditioning through Day 100; All-Cause Mortality: Conditioning through 5 year
Adverse Event Reporting Description	No Serious Adverse Events reported were related to the investigational cell product, but to the transplant or other indications.
Arm/Group Title	Overall Study Participants
Arm/Group Description	CD34+ enriched allogeneic peripheral blood stem cells (PBSC) followed by CD45RA+ T-cell-depleted allogeneic PBSC and tacrolimus for GVHD prophylaxis
All Cause Mortality
	Overall Study Participants
	Affected / at Risk (%)	# Events
Total	13/41 (31.7%)
Serious Adverse Events
	Overall Study Participants
	Affected / at Risk (%)	# Events
Total	39/41 (95.1%)
Cardiac disorders
Pericardial effusion	1/41 (2.4%)	1
Pericarditis	1/41 (2.4%)	1
Gastrointestinal disorders
Abdominal pain	2/41 (4.9%)	2
Colitis	1/41 (2.4%)	1
Diarrhea	1/41 (2.4%)	1
Enterocolitis	1/41 (2.4%)	1
Esophageal hemorrhage	1/41 (2.4%)	1
Mucositis, oral	36/41 (87.8%)	37
Nausea	3/41 (7.3%)	3
Rectal pain	1/41 (2.4%)	1
Infections and infestations
Bladder infection	2/41 (4.9%)	2
Catheter related infection	9/41 (22%)	9
Duodenal infection	1/41 (2.4%)	1
Coagulase-negative staph bacteremia	8/41 (19.5%)	8
Clostridium difficile infection	3/41 (7.3%)	3
CMV reactivation	20/41 (48.8%)	20
E Coli Bacteremia	2/41 (4.9%)	2
Leptotrichia buccalis infection	1/41 (2.4%)	1
MRSA bacteremia	1/41 (2.4%)	1
Candida Glabrata	1/41 (2.4%)	1
Enterococcus faecium	1/41 (2.4%)	1
Strep mitis	2/41 (4.9%)	2
Strep Viridans	2/41 (4.9%)	2
VRE bacteremia	2/41 (4.9%)	2
Lung infection	2/41 (4.9%)	2
Sepsis	3/41 (7.3%)	3
Sinusitis	1/41 (2.4%)	1
Investigations
Neutrophil count decreased	1/41 (2.4%)	1
Metabolism and nutrition disorders
Anorexia	3/41 (7.3%)	3
Dehydration	3/41 (7.3%)	3
Musculoskeletal and connective tissue disorders
Arthralgia	1/41 (2.4%)	1
Back Pain	1/41 (2.4%)	1
Generalized muslce weakness	1/41 (2.4%)	1
Pain in extremity	1/41 (2.4%)	1
Nervous system disorders
Headache	1/41 (2.4%)	1
Renal and urinary disorders
Acute Kidney Injury	4/41 (9.8%)	4
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary hemorrhage	2/41 (4.9%)	3
Epistaxis	2/41 (4.9%)	2
Hypoxia	3/41 (7.3%)	3
Laryngeal edema	1/41 (2.4%)	1
Respiratory failure	2/41 (4.9%)	2
Aspiration Pneumonia	1/41 (2.4%)	1
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysesthesia	2/41 (4.9%)	2
Vascular disorders
Hypotension	7/41 (17.1%)	7
Other (Not Including Serious) Adverse Events
	Overall Study Participants
	Affected / at Risk (%)	# Events
Total	41/41 (100%)
Blood and lymphatic system disorders
Anemia	8/41 (19.5%)
Gastrointestinal disorders
Diarrhea	19/41 (46.3%)
Nausea	8/41 (19.5%)
Investigations
Lymphocyte count decreased	34/41 (82.9%)
Neutrophil count decreased	16/41 (39%)
Platelet count decreased	13/41 (31.7%)
White blood cell decreased	15/41 (36.6%)
CD4 lymphocytes decreased	33/41 (80.5%)
Metabolism and nutrition disorders
Hyperglycemia	15/41 (36.6%)
Hyponatremia	5/41 (12.2%)
Hypophosphatemia	6/41 (14.6%)
Anorexia	5/41 (12.2%)
Skin and subcutaneous tissue disorders
Rash maculo-papular	5/41 (12.2%)
Vascular disorders
Hypertenstion	11/41 (26.8%)

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.