Rituximab, Pentostatin, Cyclophosphamide, and Lenalidomide in Treating Patients With Previously Untreated B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT00602836
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 45
• Locations: 3
• Arm: 1
• Actual Duration (Months): 115.4
• Patients Per Site: 15
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as pentostatin and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Lenalidomide may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving rituximab together with combination chemotherapy and lenalidomide may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving rituximab together with pentostatin, cyclophosphamide, and lenalidomide works in treating patients with previously untreated B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Leukemia; Lymphoma	Biological: Rituximab; Drug: Cyclophosphamide; Drug: Lenalidomide; Drug: Pentostatin	Phase 2

Detailed Description

OBJECTIVES:

Primary

• To assess the rate of complete and overall response using pentostatin, cyclophosphamide, and rituximab (PCR) followed by consolidation with lenalidomide in patients with previously untreated B-cell chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma.

Secondary

• To assess the proportion of patients who convert from a nodular partial response (nPR), PR, or stable disease after completing PCR to a complete response (CR) after 6 cycles of consolidation with lenalidomide.

• To assess the proportion of patients who convert from a CR with detectable minimal residual disease (MRD) after PCR to a CR with MRD negative state after 6 courses of consolidation with lenalidomide.

• To assess the proportion of patients who convert from a CR with detectable MRD, nPR, PR, or stable disease with residual disease after PCR to a CR with MRD negative state after 6 cycles of consolidation with lenalidomide.

• To monitor and assess toxicity of this regimen.

• To determine if molecular prognostic parameters (e.g., ZAP-70, CD38, cytogenetic abnormalities identified by FISH, IgVH mutation status) relate to response to PCR-lenalidomide therapy.

• To use evaluation of MRD to determine the duration of lenalidomide therapy.

• To determine the progression-free survival in CLL patients using this treatment regimen.

OUTLINE: This is a multicenter study.

• Induction therapy: Patients receive rituximab IV over 4 hours on days 1 and 2 of course 1, and over 1 hour on day 1 of each subsequent course. Patients also receive pentostatin IV over 30 minutes and cyclophosphamide IV over 30 minutes on day 1, and pegfilgrastim subcutaneously on day 2. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

• Consolidation therapy: Beginning 2 months after completion of induction therapy, patients receive oral lenalidomide once daily on days 1-28. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

• Continuation therapy: Patients with residual disease continue to receive lenalidomide as in consolidation therapy until they achieve a minimal residual disease-negative status or complete remission. Patients who achieve complete response with no detectable disease discontinue therapy and enter the observation phase.

Blood samples are collected periodically during treatment for translational and pharmacologic studies. Samples are analyzed for immunoglobulin heavy chain gene mutational status, ZAP-70 status, and levels of VEGF, bFGF, thrombospondin, and TGF-beta by ELISA; and for the effects of therapy on immune function. Samples are also stored for future research. Bone marrow aspirate samples are analyzed for minimal residual disease by flow cytometry.

After completion of study treatment, patients are followed every 90 days for 3 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 45 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Pentostatin, Cyclophosphamide, and Rituximab Followed by Consolidation With Lenalidomide for Previously Untreated B-Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)
• Actual Study Start Date: Feb 1, 2008
• Actual Primary Completion Date: Dec 1, 2010
• Actual Study Completion Date: Sep 12, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: PCR-Lenalidomide Pentostatin, Cyclophosphamide, Rituximab + Lenalidomide

Biological: Rituximab; Cycle 1: 100 mg by IV on day 1, 375 mg/m^2 by IV on day 2 Cycle 2-6: 375 mg/m^2 by IV on day 1 (every 21 days); Drug: Cyclophosphamide; 600 mg/m^2 by IV on day 1 of cycles 1-6 (every 21 days); Drug: Lenalidomide; Cycle 7: 5 mg orally daily on days 1-28 Cycle 8: 10 mg orally daily on days 1-28 as tolerability permits Cycle 9 and beyond: 10 mg orally daily on days 1-28; Drug: Pentostatin; 2 mg/m^2 by IV on day 1 of cycles 1-6 (every 21 days)

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Complete Response (CR) [12 months]

   A complete response, as defined by the National Cancer Institute Working Group (NCIWG), requires all of the following for a period of at least 2 months: - CR: no lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms; normal complete blood count; confirmed by bone marrow (BM) aspirate & biopsy

Secondary Outcome Measures

1. Number of Participants Who Convert From a Nodular Partial Response (nPR), Partial Response (PR), or Stable Disease (SD) After Pentostatin, Cyclophosphamide, and Rituximab (PCR) to a Complete Response (CR) After 6 Courses of Consolidation With Lenalidomide [12 months]

   According to the NCIWG criteria, response is defined as follows: nPR: Meets all criteria for CR, as described above, except the presence of residual clonal nodules in the bone marrow PR: 50% decrease in peripheral blood lymphocytes, lymphadenopathy, liver/spleen size, presence/absence of constitutional symptoms; plus ≥1 of the following: ≥1500/μL polymorphonuclear leukocytes, >100000/μL platelets, >11.0 g/dL hemoglobin or 50% improvement for these parameters without transfusions SD: participant who does not meet any of the criteria described above

2. Number of Participants Who Convert From a CR With Minimal Residual Disease (MRD) Positive Status After PCR to a CR With MRD-negative Status After 6 Courses of Consolidation With Lenalidomide [12 months]

   MRD refers to small number of leukemic cells that remain in the participant during treatment or after treatment when the participant has achieved CR. For all participants who achieved CR, the follow-up bone marrow sample was tested for malignant B cells to determine if there was any MRD.

3. Number of Participants With a Response (CR, nPR, PR) [During treatment (up to 5 years)]

   Response criteria described in above outcomes.

4. Overall Survival (OS) [time from registration to death (up to 5 years)]

   Overall Survival (OS) was defined as the time from registration to death of any cause. Participants were followed for a maximum of 5 years from registration. The median OS with 95% CI was estimated using the Kaplan Meier method.

5. Treatment Free Survival (TFS) [time from registration to progression (up to 5 years)]

   Treatment Free Survival (TFS) was defined as the time from registration to the earliest date documentation of subsequent treatment or death, whichever came first. Participants were followed for a maximum of 5 years from registration. The median TFS with 95% CI was estimated using the Kaplan Meier method.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), meeting the following criteria:

• Biopsy-proven SLL according to WHO criteria

• CLL diagnosis* according to NCI working group criteria as evidenced by all of the following:

• Peripheral blood lymphocyte count of > 5,000/mm³

• Small to moderate peripheral blood lymphocyte with < 55% prolymphocytes

• Immunophenotyping consistent with CLL defined as:

• B-cell markers with CD5 antigen in the absence of other pan-T-cell markers (e.g., CD3, CD2)

• CD19, CD20, or CD23

• Dim surface immunoglobulin expression

• Exclusively kappa or lambda light chains

• Diagnosis of mantle cell lymphoma must be excluded by negative FISH analysis for t(11;14)(IgH/CCND1) on peripheral blood or tissue biopsy or negative immunohistochemical stains for cyclin D1 on involved tissue biopsy NOTE: *Splenomegaly, hepatomegaly, or lymphadenopathy are not required for the diagnosis of CLL

• Previously untreated disease and meets ≥ 1 of the following criteria*:

• At least 1 or more of the following disease-related symptoms:

• Weight loss > 10% within the previous 6 months

• Extreme fatigue attributed to CLL

• Fevers > 100.5º F for 2 weeks without evidence of infection

• Night sweats without evidence of infection

• Evidence of progressive marrow failure as manifested by the development of or worsening anemia (i.e., hemoglobin ≤ 11 g/dL) and/or thrombocytopenia (i.e., platelet count ≤ 100,000/mm³) not due to autoimmune disease

• Symptomatic or progressive lymphadenopathy, splenomegaly, or hepatomegaly

• Progressive lymphocytosis due to CLL with an increase of > 50% over a 2-month period or an anticipated doubling time < 6 months NOTE: *Marked hypogammaglobulinemia or the development of a monoclonal protein in the absence of any of the above criteria for active disease are not sufficient for protocol therapy

PATIENT CHARACTERISTICS:

• ECOG performance status 0-3

• Serum creatinine ≤ 1.5 times upper limit of normal (ULN)

• Total bilirubin ≤ 3.0 times ULN (unless due to Gilbert disease)

• Direct bilirubin < 1.5 mg/dL for Gilbert disease to be diagnosed if total bilirubin > 3.0 times ULN

• AST and ALT ≤ 3.0 times ULN (unless due to hemolysis or CLL)

• Willing to provide blood samples

• Able to take acetylsalicylic acid (ASA) (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use low molecular weight heparin)

• Not pregnant or nursing

• Negative pregnancy test

• Female patients must use effective double-method contraception beginning 1 month prior to, during, and for 4 weeks after completion of study treatment

• Male patients must use effective contraception during and for 4 weeks after completion of study treatment

• No comorbid conditions, including any of the following:

• New York Heart Association class III or IV heart disease

• Recent myocardial infarction (< 1 month)

• Uncontrolled infection

• Infection with HIV/AIDS

• No other active primary malignancy requiring treatment or that limits survival to ≤ 2 years

• No history of deep venous thrombosis or pulmonary embolism ≤ 12 months prior to study registration

• No active hemolytic anemia requiring immunosuppressive or other pharmacologic therapy

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior chemotherapy or monoclonal antibody-based therapy for treatment of CLL

• Nutraceutical treatments with no established benefit in CLL (e.g., epigallocatechin gallate or other herbal treatments) are not considered prior therapy

• More than 4 weeks since prior radiotherapy

• At least 4 weeks since prior major surgery

• No concurrent corticosteroids

• Concurrent low doses of steroids (e.g., < 10 mg of prednisone or equivalent dose of other steroid) used for treatment of non-hematologic medical conditions allowed

• Prior use of corticosteroids allowed

• No prior thalidomide or lenalidomide

• No concurrent therapeutic doses of coumadin-derivative anticoagulants (e.g., warfarin)

• Doses of ≤ 2 mg daily allowed for thrombosis prophylaxis

• Prophylactic doses of low molecular weight heparin allowed

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Scottsdale	Scottsdale	Arizona	United States	85259-5499
2	Mayo Clinic - Jacksonville	Jacksonville	Florida	United States	32224
3	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Mayo Clinic
• National Cancer Institute (NCI)

Investigators

• Study Chair: Tait D. Shanafelt, MD, Mayo Clinic
• Principal Investigator: Han Win Tun, MD, Mayo Clinic
• Principal Investigator: Jose F. Leis, MD, PhD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mayo Clinic
• ClinicalTrials.gov Identifier: NCT00602836
• Other Study ID Numbers: CDR0000582676; P30CA015083; MC0784; 07-002156; RV-CLL-PI-146; NCI-2009-01281
• First Posted: Jan 28, 2008
• Last Update Posted: Jan 27, 2020
• Last Verified: Sep 1, 2017

• Keywords provided by Mayo Clinic: B-cell chronic lymphocytic leukemia; stage I chronic lymphocytic leukemia; stage II chronic lymphocytic leukemia; stage III chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia; contiguous stage II small lymphocytic lymphoma; noncontiguous stage II small lymphocytic lymphoma; stage I small lymphocytic lymphoma; stage III small lymphocytic lymphoma; stage IV small lymphocytic lymphoma
• Additional relevant MeSH terms: Lymphoma; Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Cyclophosphamide; Rituximab; Lenalidomide; Pentostatin

Study Results

Participant Flow

Recruitment Details	Forty-five (45) participants were recruited at Mayo Clinic (Rochester, Florida and Arizona) between March 2009 and December 2009.
Pre-assignment Detail	One participant was deemed ineligible and is excluded from all analyses per study design.

Arm/Group Title	PCR-Lenalidomide
Arm/Group Description	Pentostatin, Cyclophosphamide, Rituximab + Lenalidomide
Period Title: Overall Study
STARTED	44
COMPLETED	39
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	PCR-Lenalidomide
Arm/Group Description	Pentostatin, Cyclophosphamide, Rituximab + Lenalidomide
Overall Participants	44
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	65
Sex: Female, Male (Count of Participants)
Female	13 29.5%
Male	31 70.5%
Region of Enrollment (participants) [Number]
United States	44 100%
Fluorescence In Situ Hybridization (FISH) Abnormalities (participants) [Number]
deletion(13q14.2)	13 29.5%
Trisomy 12	7 15.9%
deletion (11q22)	6 13.6%
17p-	1 2.3%
Other	2 4.5%
Normal	15 34.1%
Rai Stage (participants) [Number]
Stage I-II	27 61.4%
Stage III-IV	17 38.6%
ZAP-70 Status (participants) [Number]
Positive (>=20%)	24 54.5%
Negative (<20%)	20 45.5%
CD38 Status (participants) [Number]
Positive (>=30%)	14 31.8%
Negative (<30%)	30 68.2%
Immunoglobulin Variable Heavy Chain (IGVH) Mutation Status (participants) [Number]
Unmutated	22 50%
Mutated	20 45.5%
Not tested	2 4.5%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Complete Response (CR)
Description	A complete response, as defined by the National Cancer Institute Working Group (NCIWG), requires all of the following for a period of at least 2 months: - CR: no lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms; normal complete blood count; confirmed by bone marrow (BM) aspirate & biopsy
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PCR-Lenalidomide
Arm/Group Description	Pentostatin, Cyclophosphamide, Rituximab + Lenalidomide
Measure Participants	44
Number [participants]	14 31.8%

2. Secondary Outcome

Title	Number of Participants Who Convert From a Nodular Partial Response (nPR), Partial Response (PR), or Stable Disease (SD) After Pentostatin, Cyclophosphamide, and Rituximab (PCR) to a Complete Response (CR) After 6 Courses of Consolidation With Lenalidomide
Description	According to the NCIWG criteria, response is defined as follows: nPR: Meets all criteria for CR, as described above, except the presence of residual clonal nodules in the bone marrow PR: 50% decrease in peripheral blood lymphocytes, lymphadenopathy, liver/spleen size, presence/absence of constitutional symptoms; plus ≥1 of the following: ≥1500/μL polymorphonuclear leukocytes, >100000/μL platelets, >11.0 g/dL hemoglobin or 50% improvement for these parameters without transfusions SD: participant who does not meet any of the criteria described above
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

All patients that began lenalidomide consolidation with either and nPR, PR, or SD were included in this analysis.

Arm/Group Title	PCR-Lenalidomide
Arm/Group Description	Pentostatin, Cyclophosphamide, Rituximab + Lenalidomide
Measure Participants	21
Count of Participants [Participants]	5 11.4%

3. Secondary Outcome

Title	Number of Participants Who Convert From a CR With Minimal Residual Disease (MRD) Positive Status After PCR to a CR With MRD-negative Status After 6 Courses of Consolidation With Lenalidomide
Description	MRD refers to small number of leukemic cells that remain in the participant during treatment or after treatment when the participant has achieved CR. For all participants who achieved CR, the follow-up bone marrow sample was tested for malignant B cells to determine if there was any MRD.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

All patients that began consolidation with a CR and MRD-negative status were included in this analysis.

Arm/Group Title	PCR-Lenalidomide
Arm/Group Description	Pentostatin, Cyclophosphamide, Rituximab + Lenalidomide
Measure Participants	5
Count of Participants [Participants]	4 9.1%

4. Secondary Outcome

Title	Number of Participants With a Response (CR, nPR, PR)
Description	Response criteria described in above outcomes.
Time Frame	During treatment (up to 5 years)

Outcome Measure Data

Analysis Population Description

All patients that registered to this trial with the intent-to-treat were included in this analysis.

Arm/Group Title	PCR-Lenalidomide
Arm/Group Description	Pentostatin, Cyclophosphamide, Rituximab + Lenalidomide
Measure Participants	44
Count of Participants [Participants]	38 86.4%

5. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall Survival (OS) was defined as the time from registration to death of any cause. Participants were followed for a maximum of 5 years from registration. The median OS with 95% CI was estimated using the Kaplan Meier method.
Time Frame	time from registration to death (up to 5 years)

Outcome Measure Data

Analysis Population Description

All patients who registered were included in this analysis.

Arm/Group Title	PCR-Lenalidomide
Arm/Group Description	Pentostatin, Cyclophosphamide, Rituximab + Lenalidomide
Measure Participants	44
Median (95% Confidence Interval) [months]	NA

6. Secondary Outcome

Title	Treatment Free Survival (TFS)
Description	Treatment Free Survival (TFS) was defined as the time from registration to the earliest date documentation of subsequent treatment or death, whichever came first. Participants were followed for a maximum of 5 years from registration. The median TFS with 95% CI was estimated using the Kaplan Meier method.
Time Frame	time from registration to progression (up to 5 years)

Outcome Measure Data

Analysis Population Description

All patients that registered to treatment were included in this analysis.

Arm/Group Title	PCR-Lenalidomide
Arm/Group Description	Pentostatin, Cyclophosphamide, Rituximab + Lenalidomide
Measure Participants	44
Median (95% Confidence Interval) [months]	NA

Adverse Events

Arm/Group Title	PCR-Lenalidomide
Arm/Group Description	Pentostatin, Cyclophosphamide, Rituximab + Lenalidomide
All Cause Mortality
	PCR-Lenalidomide
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	PCR-Lenalidomide
	Affected / at Risk (%)	# Events
Total	9/44 (20.5%)
Cardiac disorders
Atrial flutter	1/44 (2.3%)	1
Gastrointestinal disorders
Nausea	1/44 (2.3%)	1
Infections and infestations
Upper airway infection	1/44 (2.3%)	1
Urinary tract infection	1/44 (2.3%)	1
Investigations
Neutrophil count decreased	4/44 (9.1%)	6
Platelet count decreased	1/44 (2.3%)	1
Respiratory, thoracic and mediastinal disorders
Pneumonitis	2/44 (4.5%)	2
Other (Not Including Serious) Adverse Events
	PCR-Lenalidomide
	Affected / at Risk (%)	# Events
Total	44/44 (100%)
Blood and lymphatic system disorders
Anemia	40/44 (90.9%)	231
Febrile neutropenia	1/44 (2.3%)	1
Cardiac disorders
Atrial fibrillation	2/44 (4.5%)	2
Atrial flutter	1/44 (2.3%)	1
Left ventricular failure	1/44 (2.3%)	4
Restrictive cardiomyopathy	1/44 (2.3%)	1
Gastrointestinal disorders
Abdominal distension	1/44 (2.3%)	1
Abdominal pain	1/44 (2.3%)	1
Constipation	1/44 (2.3%)	1
Diarrhea	2/44 (4.5%)	2
Flatulence	1/44 (2.3%)	1
Nausea	6/44 (13.6%)	11
Small intestinal obstruction	1/44 (2.3%)	1
Vomiting	4/44 (9.1%)	8
General disorders
Chills	4/44 (9.1%)	4
Edema limbs	1/44 (2.3%)	1
Fatigue	28/44 (63.6%)	116
Fever	20/44 (45.5%)	26
Pain-Chest	1/44 (2.3%)	1
Syndromes	1/44 (2.3%)	1
Hepatobiliary disorders
Gallbladder pain	1/44 (2.3%)	2
Immune system disorders
Hypersensitivity	3/44 (6.8%)	3
Infections and infestations
Abdominal infection	1/44 (2.3%)	1
Arthritis infective	1/44 (2.3%)	1
Blood Infection	1/44 (2.3%)	1
Infection without neutropenia	2/44 (4.5%)	2
Lymph gland infection	1/44 (2.3%)	1
Lymphatic infection	1/44 (2.3%)	2
Pneumonia	2/44 (4.5%)	2
Respiratory tract infection	4/44 (9.1%)	4
Sinus infection	1/44 (2.3%)	1
Sinusitis	2/44 (4.5%)	2
Skin (cellulites) infection	1/44 (2.3%)	1
Upper airway infection	2/44 (4.5%)	2
Urinary tract infection	1/44 (2.3%)	1
Investigations
Aspartate aminotransferase increased	1/44 (2.3%)	1
Bilirubin	1/44 (2.3%)	1
Leukopenia	34/44 (77.3%)	227
Neutrophil count decreased	38/44 (86.4%)	231
Platelet count decreased	32/44 (72.7%)	262
Metabolism and nutrition disorders
Anorexia	4/44 (9.1%)	6
Dehydration	1/44 (2.3%)	3
Hyponatremia	2/44 (4.5%)	3
Musculoskeletal and connective tissue disorders
Arthralgia	1/44 (2.3%)	1
Bone pain	1/44 (2.3%)	1
Myalgia	4/44 (9.1%)	4
Nervous system disorders
Headache	1/44 (2.3%)	1
Peripheral sensory neuropathy	1/44 (2.3%)	1
Psychiatric disorders
Insomnia	1/44 (2.3%)	1
Renal and urinary disorders
Urinary frequency	1/44 (2.3%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/44 (2.3%)	1
Dyspnea	4/44 (9.1%)	9
Hypoxia	1/44 (2.3%)	1
Pneumonitis	1/44 (2.3%)	1
Pulmonary hypertension	1/44 (2.3%)	1
Skin and subcutaneous tissue disorders
Photosensitivity	1/44 (2.3%)	1
Pruritus	2/44 (4.5%)	3
Rash	25/44 (56.8%)	48
Sweating	2/44 (4.5%)	2
Vascular disorders
Flushing	1/44 (2.3%)	1
Hot flashes	1/44 (2.3%)	1
Hypertension	2/44 (4.5%)	3

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.