Trial Outcomes & Findings for Clofarabine for Myelodysplastic Syndrome (MDS) Patients Who Failed Vidaza Treatment (tx) (NCT NCT00700011)

Last Updated: 2013-03-15

Results Overview

Hematologic improvement will be an increased Hemoglobin of 1.5 g/dL or a reduction in the need for PRBC transfusions by at least 4 units over an 8 week period, at least 100% increase and an ANC of \>0.5 x 10\^9/L and an absolut platelet count increase of \>30 x 10\^9/L for patients who start at \> 20 x 10\^9/L, or increase from \<20 x 10\^9/L to \>20 x 10\^9/L and by at least 100%.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

10 participants

Primary outcome timeframe

2-3 months

Results posted on

2013-03-15

Participant Flow

The recruitment period started 3/24/08 (date of consent of the first patient), to 4/8/10 which was the date IRB lists as date of study closure. All patients were consented and treated at our clinic, Texas Oncology - Amarillo. Eight patients were treated to the 10 mg/m2 arm and two patients to the 5 mg/m2 arm. Study closed due to poor recruitment.

There were no screen fails due to pre-screening thoroughly. The plan was to sign eight patients to the 10 mg/m2 arm and then eight to the 5 mg/m2 arm, but recuitment was difficult and decision was made to close study in early 2010, so only two patients were assigned to 5 mg/m2 arm.

Participant milestones

Participant milestones
Measure	10 mg/m2 Group Patients were treated with Clofarabine 10 mg/m2 daily x 5 days per cycle. Cycles were intended on being every 28 days but this was flexible due to the bone marrow neding to recover from each cycle before strting the next one. Neulasta was given on day 5 of each cycle. Patients were treated until disease progression, or intolerable toxicities.	5 mg/m2 Group Patients were treated with Clofarabine 10 mg/m2 daily x 5 days per cycle. Cycles were intended on being every 28 days but this was flexible due to the bone marrow neding to recover from each cycle before strting the next one. Neulasta was given on day 5 of each cycle. Patients were treated until disease progression, or intolerable toxicities.
Overall Study STARTED	8	2
Overall Study COMPLETED	8	1
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	10 mg/m2 Group Patients were treated with Clofarabine 10 mg/m2 daily x 5 days per cycle. Cycles were intended on being every 28 days but this was flexible due to the bone marrow neding to recover from each cycle before strting the next one. Neulasta was given on day 5 of each cycle. Patients were treated until disease progression, or intolerable toxicities.	5 mg/m2 Group Patients were treated with Clofarabine 10 mg/m2 daily x 5 days per cycle. Cycles were intended on being every 28 days but this was flexible due to the bone marrow neding to recover from each cycle before strting the next one. Neulasta was given on day 5 of each cycle. Patients were treated until disease progression, or intolerable toxicities.
Overall Study Death	0	1

Baseline Characteristics

Clofarabine for Myelodysplastic Syndrome (MDS) Patients Who Failed Vidaza Treatment (tx)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	10 mg/m2 Group n=8 Participants Patients were treated with Clofarabine 10 mg/m2 daily x 5 days per cycle. Cycles were intended on being every 28 days but this was flexible due to the bone marrow neding to recover from each cycle before strting the next one. Neulasta was given on day 5 of each cycle. Patients were treated until disease progression, or intolerable toxicities.	5 mg/m2 Group n=2 Participants Patients were treated with Clofarabine 10 mg/m2 daily x 5 days per cycle. Cycles were intended on being every 28 days but this was flexible due to the bone marrow neding to recover from each cycle before strting the next one. Neulasta was given on day 5 of each cycle. Patients were treated until disease progression, or intolerable toxicities.	Total n=10 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	8 Participants n=5 Participants	2 Participants n=7 Participants	10 Participants n=5 Participants
Age Continuous	73.38 years STANDARD_DEVIATION 4.10357 • n=5 Participants	77.5 years STANDARD_DEVIATION 0.707 • n=7 Participants	74.2 years STANDARD_DEVIATION 4.022 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment United States	8 participants n=5 Participants	2 participants n=7 Participants	10 participants n=5 Participants

PRIMARY outcome

Timeframe: 2-3 months

Population: All patients considered for analysis except for one on the 5 mg/m2 arm who died within 2 weeks after cycle one making this unassessable for that patient.

Outcome measures

Outcome measures
Measure	10 mg/m2 Group n=8 Participants Patients were treated with Clofarabine 10 mg/m2 daily x 5 days per cycle. Cycles were intended on being every 28 days but this was flexible due to the bone marrow neding to recover from each cycle before strting the next one. Neulasta was given on day 5 of each cycle. Patients were treated until disease progression, or intolerable toxicities.	5 mg/m2 Group n=1 Participants Patients were treated with Clofarabine 5 mg/m2 daily x 5 days per cycle. Cycles were intended on being every 28 days but this was flexible due to the bone marrow neding to recover from each cycle before strting the next one. Neulasta was given on day 5 of each cycle. Patients were treated until disease progression, or intolerable toxicities.
Improvement in Peripheral Blood Count and Reduction in Number of Transfusions	3 participants	1 participants

PRIMARY outcome

Timeframe: 2-3 months

Population: All patients considered except one on the 5 mg/m2 arm who we didn't have enough time to assess response as he died within 2 weeks after receiving cycle 1.

The International Working Group response criteria was used. Complete remission is defined as \<5 % marrow blasts without evidence of dysplasia and normalization of the peripheral blood counts, including hemoglobin \>11 g/dL, neutrophil count of \>1 x 10\^9/L. and platelet count of \>100 x 10\^9/L. Patients must also be transfusion-independent and not require any recombinant erythropoietin. Partial remission (PR) is defined as: satisfying complete remission criteria if abnormal before treatment, except that blasts are reduced by 50% or more compared to pretreatment levels, but still \>5 %. Stable disease is defined as: failure to achieve at least a PR but without evidence of disease progression for at least 8 weeks.Progression of disease is defined as: disease progression with worsening cytopenias. Best response of these patients is used in the determination for this outcome below.

Outcome measures

Outcome measures
Measure	10 mg/m2 Group n=8 Participants Patients were treated with Clofarabine 10 mg/m2 daily x 5 days per cycle. Cycles were intended on being every 28 days but this was flexible due to the bone marrow neding to recover from each cycle before strting the next one. Neulasta was given on day 5 of each cycle. Patients were treated until disease progression, or intolerable toxicities.	5 mg/m2 Group n=1 Participants Patients were treated with Clofarabine 5 mg/m2 daily x 5 days per cycle. Cycles were intended on being every 28 days but this was flexible due to the bone marrow neding to recover from each cycle before strting the next one. Neulasta was given on day 5 of each cycle. Patients were treated until disease progression, or intolerable toxicities.
Determine Frequency and Duration of Bone Marrow Responses to IV Clofarabine complete remission	1 participants	0 participants
Determine Frequency and Duration of Bone Marrow Responses to IV Clofarabine partial remission	1 participants	0 participants
Determine Frequency and Duration of Bone Marrow Responses to IV Clofarabine stable disease	4 participants	1 participants
Determine Frequency and Duration of Bone Marrow Responses to IV Clofarabine progressive disease	2 participants	0 participants

PRIMARY outcome

Timeframe: biweekly for duration of treatment , an average of 3 months

Population: All participants considered.

Assess for adverse events in all the patients receiving the Clofarabine at the dose schedules described in the protocol (CTCAE 3.0 used).

Outcome measures

Outcome measures
Measure	10 mg/m2 Group n=8 Participants Patients were treated with Clofarabine 10 mg/m2 daily x 5 days per cycle. Cycles were intended on being every 28 days but this was flexible due to the bone marrow neding to recover from each cycle before strting the next one. Neulasta was given on day 5 of each cycle. Patients were treated until disease progression, or intolerable toxicities.	5 mg/m2 Group n=2 Participants Patients were treated with Clofarabine 5 mg/m2 daily x 5 days per cycle. Cycles were intended on being every 28 days but this was flexible due to the bone marrow neding to recover from each cycle before strting the next one. Neulasta was given on day 5 of each cycle. Patients were treated until disease progression, or intolerable toxicities.
To Determine the Non-hematologic Toxicity Profile of This Dose Schedule (Grade 2 and Above) Headache	1 participants	0 participants
To Determine the Non-hematologic Toxicity Profile of This Dose Schedule (Grade 2 and Above) Fatigue	4 participants	1 participants
To Determine the Non-hematologic Toxicity Profile of This Dose Schedule (Grade 2 and Above) Mucositis	1 participants	1 participants
To Determine the Non-hematologic Toxicity Profile of This Dose Schedule (Grade 2 and Above) Vomiting	2 participants	1 participants
To Determine the Non-hematologic Toxicity Profile of This Dose Schedule (Grade 2 and Above) Nausea	2 participants	1 participants
To Determine the Non-hematologic Toxicity Profile of This Dose Schedule (Grade 2 and Above) Hyperbilirubinemia	1 participants	1 participants
To Determine the Non-hematologic Toxicity Profile of This Dose Schedule (Grade 2 and Above) Dehydration	1 participants	1 participants
To Determine the Non-hematologic Toxicity Profile of This Dose Schedule (Grade 2 and Above) Rash	1 participants	0 participants
To Determine the Non-hematologic Toxicity Profile of This Dose Schedule (Grade 2 and Above) ALT elevation	1 participants	0 participants
To Determine the Non-hematologic Toxicity Profile of This Dose Schedule (Grade 2 and Above) AST elevation	1 participants	0 participants
To Determine the Non-hematologic Toxicity Profile of This Dose Schedule (Grade 2 and Above) Dyspnea	0 participants	1 participants
To Determine the Non-hematologic Toxicity Profile of This Dose Schedule (Grade 2 and Above) Dizziness	1 participants	0 participants
To Determine the Non-hematologic Toxicity Profile of This Dose Schedule (Grade 2 and Above) Pulmonary edema	0 participants	1 participants

SECONDARY outcome

Timeframe: assessed twice per cycle

Population: All participants were considered except one patient on 5 mg/m2 arm who died within 2 weeks after cycle 1, so this was unassessable.

Since we previously observed decreases in DNA methylation in tumor cells after in vitro treatment with Clofarabine, we compared the long interspersednuclear element-1 methylation of genomic DNA obtained from CD3-depletedperipheral blood mononuclear cells between day 1 and day 5 of each cycle of Clofarabine.

Outcome measures

Outcome measures
Measure	10 mg/m2 Group n=8 Participants Patients were treated with Clofarabine 10 mg/m2 daily x 5 days per cycle. Cycles were intended on being every 28 days but this was flexible due to the bone marrow neding to recover from each cycle before strting the next one. Neulasta was given on day 5 of each cycle. Patients were treated until disease progression, or intolerable toxicities.	5 mg/m2 Group n=1 Participants Patients were treated with Clofarabine 5 mg/m2 daily x 5 days per cycle. Cycles were intended on being every 28 days but this was flexible due to the bone marrow neding to recover from each cycle before strting the next one. Neulasta was given on day 5 of each cycle. Patients were treated until disease progression, or intolerable toxicities.
Number of Participants With DNA Hypomethylation During the Study	2 participants	0 participants

Adverse Events

10 mg/m2 Group

Serious events: 6 serious events

Other events: 8 other events

Deaths: 0 deaths

5 mg/m2 Group

Serious events: 2 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	10 mg/m2 Group n=8 participants at risk Patients were treated with Clofarabine 10 mg/m2 daily x 5 days per cycle. Cycles were intended on being every 28 days but this was flexible due to the bone marrow neding to recover from each cycle before strting the next one. Neulasta was given on day 5 of each cycle. Patients were treated until disease progression, or intolerable toxicities.	5 mg/m2 Group n=2 participants at risk Patients were treated with Clofarabine 10 mg/m2 daily x 5 days per cycle. Cycles were intended on being every 28 days but this was flexible due to the bone marrow neding to recover from each cycle before strting the next one. Neulasta was given on day 5 of each cycle. Patients were treated until disease progression, or intolerable toxicities.
Blood and lymphatic system disorders Thrombocytopenia	25.0% 2/8 • Number of events 2 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.	100.0% 2/2 • Number of events 4 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.
Infections and infestations Infection w/ a Grade 3-4 ANC	50.0% 4/8 • Number of events 6 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.	50.0% 1/2 • Number of events 2 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.
Respiratory, thoracic and mediastinal disorders Pneumonia	12.5% 1/8 • Number of events 1 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.	0.00% 0/2 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.
Infections and infestations Infection w/ Normal ANC	12.5% 1/8 • Number of events 2 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.	0.00% 0/2 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.
Blood and lymphatic system disorders Hemorrhage - Nosebleed	12.5% 1/8 • Number of events 1 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.	0.00% 0/2 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.
Gastrointestinal disorders Dehydration	12.5% 1/8 • Number of events 1 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.	0.00% 0/2 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.
Blood and lymphatic system disorders Neutropenia	12.5% 1/8 • Number of events 1 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.	0.00% 0/2 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.
Infections and infestations Infection w/ Grade 1-2 ANC	12.5% 1/8 • Number of events 1 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.	0.00% 0/2 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.
Respiratory, thoracic and mediastinal disorders Pulmonary Infiltrates	12.5% 1/8 • Number of events 1 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.	0.00% 0/2 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.
Investigations Infection - Skin (cellulitis)	12.5% 1/8 • Number of events 1 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.	0.00% 0/2 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.

Other adverse events

Other adverse events
Measure	10 mg/m2 Group n=8 participants at risk Patients were treated with Clofarabine 10 mg/m2 daily x 5 days per cycle. Cycles were intended on being every 28 days but this was flexible due to the bone marrow neding to recover from each cycle before strting the next one. Neulasta was given on day 5 of each cycle. Patients were treated until disease progression, or intolerable toxicities.	5 mg/m2 Group n=2 participants at risk Patients were treated with Clofarabine 10 mg/m2 daily x 5 days per cycle. Cycles were intended on being every 28 days but this was flexible due to the bone marrow neding to recover from each cycle before strting the next one. Neulasta was given on day 5 of each cycle. Patients were treated until disease progression, or intolerable toxicities.
General disorders Fatigue	50.0% 4/8 • Number of events 6 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.	50.0% 1/2 • Number of events 1 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.
Gastrointestinal disorders Mucositis	12.5% 1/8 • Number of events 3 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.	50.0% 1/2 • Number of events 1 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.
Gastrointestinal disorders Vomiting	37.5% 3/8 • Number of events 3 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.	0.00% 0/2 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.
Gastrointestinal disorders Nausea	37.5% 3/8 • Number of events 3 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.	0.00% 0/2 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.
Gastrointestinal disorders Hyperbilirubinemia	12.5% 1/8 • Number of events 1 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.	50.0% 1/2 • Number of events 1 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.
Gastrointestinal disorders Dehydration	12.5% 1/8 • Number of events 1 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.	50.0% 1/2 • Number of events 1 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.
Skin and subcutaneous tissue disorders Rash	12.5% 1/8 • Number of events 1 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.	0.00% 0/2 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.
Metabolism and nutrition disorders ALT elevation	12.5% 1/8 • Number of events 1 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.	0.00% 0/2 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.
Metabolism and nutrition disorders AST	12.5% 1/8 • Number of events 1 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.	0.00% 0/2 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/8 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.	50.0% 1/2 • Number of events 1 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.
Nervous system disorders Dizziness	12.5% 1/8 • Number of events 1 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.	0.00% 0/2 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.
General disorders Headache	12.5% 1/8 • Number of events 1 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.	0.00% 0/2 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.
Respiratory, thoracic and mediastinal disorders Pulmonary edema	0.00% 0/8 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.	50.0% 1/2 • Number of events 1 • Adverse events were collected up to 28 days post last dose, but were followed by Dr Lim to death or lost to follow up and if any adverse events were assessed to be related to the Clofarabine they were to be added to the list collected for study.

Additional Information

Dr. Seah Lim

Texas Oncology - Amarillo

Phone: 806-358-8654

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place