Trial Outcomes & Findings for Low-dose Oral Clofarabine for the Treatment of IPSS INT-1, INT-2 or HIGH Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia (NCT NCT00708721)

Last Updated: 2017-06-01

Results Overview

Dose-limiting toxicity was defined as any nonhematologic toxicity grade 3 or greater except for alopecia or nausea (which may be of grade 4 severity), or any grade 4 hematologic toxicity lasting more than 28 days after the last day of therapy.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

11 participants

Primary outcome timeframe

28 days after the first admistration of oral clofarabine

Results posted on

2017-06-01

Participant Flow

Participant milestones

Participant milestones
Measure	Cohort 1: 5 mg/Day for 10 Days 5 mg/day for 10 out of 28 days	Cohort 2: 1 mg/Day for 10 Days 1 mg/day for 10/28 days and for cycle 1 and then 1 mg/day for 7/28 days for cycle 2 onward	Cohort 3: 1 mg/Day for 7 Days 1 mg/day for 7/28 days	Not Evaluable
Overall Study STARTED	2	4	3	2
Overall Study COMPLETED	2	4	3	2
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Low-dose Oral Clofarabine for the Treatment of IPSS INT-1, INT-2 or HIGH Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Groups n=11 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants
Age, Categorical >=65 years	7 Participants n=5 Participants
Age, Continuous	68.3 years n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants
Region of Enrollment United States	11 participants n=5 Participants

PRIMARY outcome

Timeframe: 28 days after the first admistration of oral clofarabine

Population: 9 out of 11 participants were evaluable for this outcome.

Outcome measures

Outcome measures
Measure	Cohort 1: 10 mg/Day for 10 Days n=2 Participants	Cohort 2: 1 mg/Day for 10 Days n=4 Participants	Cohort 3: 1 mg/Day for 7 Days n=3 Participants	Not Evaluable n=2 Participants
Number of Participants Who Experienced a Dose-Limiting Toxicity	2 participants who experienced a DLT	4 participants who experienced a DLT	0 participants who experienced a DLT	0 participants who experienced a DLT

PRIMARY outcome

Timeframe: 4 weeks

Population: Two patients were not eligible for analysis.

Response rate was measured as complete, partial and hematologic improvement by modified IWG criteria. For complete remission the following must be present for four weeks in a bone marrow aspirate and biopsy: \<5% myeloblasts, normal maturation of all cell lines, persisted dysplasia. Peripheral blood counts need to be hemoglobin \>11 g/dL, neutrophils \>1000/mm3, platelets\>100000/mm3, blasts 0%. Partial remission requires all criteria for complete remission except blasts decreased by \>50% over pretreatment. Stable disease is defined as failure to achieve at least partial remission, but no evidence of progression for \> 8 weeks. Failure is defined as death during tre3atment or disease progression characterized by worsening of cytopenias, increase in percentage of bone marrow blasts, or progression to a more advanced MDS FAB subtype than pretreatment.

Outcome measures

Outcome measures
Measure	Cohort 1: 10 mg/Day for 10 Days n=9 Participants	Cohort 2: 1 mg/Day for 10 Days	Cohort 3: 1 mg/Day for 7 Days	Not Evaluable
The Overall Response Rate in Response to Low Dose Daily Oral Clofarabine in Patients With High Risk Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia (Dysplastic Type).	3 participants who experienced a response	—	—	—

SECONDARY outcome

Timeframe: approximately 4 years

Population: Cycles are 28 days long. Analysis assessed the longest number of cycles completed on study until progression to AML.

Longest documented duration of time until progression to AML.

Outcome measures

Outcome measures
Measure	Cohort 1: 10 mg/Day for 10 Days n=9 Participants	Cohort 2: 1 mg/Day for 10 Days	Cohort 3: 1 mg/Day for 7 Days	Not Evaluable
Time to Progression to Acute Myeloid Leukemia (AML)	51 cycles	—	—	—

SECONDARY outcome

Timeframe: approximately 4 years

Population: Of 11 patients, 9 were evaluable for response. Two patients had stable disease responses.

Stable disease is defined as failure to achieve at least PR, but no evidence of progression for \> 8 weeks.

Outcome measures

Outcome measures
Measure	Cohort 1: 10 mg/Day for 10 Days n=9 Participants	Cohort 2: 1 mg/Day for 10 Days	Cohort 3: 1 mg/Day for 7 Days	Not Evaluable
Response of MDS Patients Treated With Low Dose Daily Oral Clofarabine.	2 Participants	—	—	—

SECONDARY outcome

Timeframe: through end of treatment

Population: Data were not collected and the outcome measure was not analyzed

Potential genomic changes following low dose daily oral clofarabine administration will be assessed.

Outcome measures

Outcome measures
Measure	Cohort 1: 10 mg/Day for 10 Days	Cohort 2: 1 mg/Day for 10 Days	Cohort 3: 1 mg/Day for 7 Days	Not Evaluable
The Effect of Low Dose Daily Oral Clofarabine on Global Methylation in Patients With MDS.	0	—	—	—

SECONDARY outcome

Timeframe: through end of treatment

Population: Data were not collected and the outcome measure was not analyzed

Assessment of potential change in miRNA and mRNA genetic expression patterns in patients following administration of low dose daily clofarabine.

Outcome measures

Outcome measures
Measure	Cohort 1: 10 mg/Day for 10 Days	Cohort 2: 1 mg/Day for 10 Days	Cohort 3: 1 mg/Day for 7 Days	Not Evaluable
The Effect of Low Dose Daily Oral Clofarabine on miRNA and mRNA Expression Patterns in Patients With MDS	0	—	—	—

SECONDARY outcome

Timeframe: To 30 days after end of treatment or until full resolution.

Population: All participants experienced at least 1 adverse event (100% of the patient population; 11/11 participants)

NCI CTCAE version 3.0 will be used to assess adverse events. The number of participants experiencing adverse events and the number of adverse events per patient will be documented through the course of study.

Outcome measures

Outcome measures
Measure	Cohort 1: 10 mg/Day for 10 Days n=11 Participants	Cohort 2: 1 mg/Day for 10 Days	Cohort 3: 1 mg/Day for 7 Days	Not Evaluable
Number of Participants With Adverse Events	11 participants experiencing adverse events	—	—	—

Adverse Events

All Groups

Serious events: 8 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	All Groups n=11 participants at risk All patients who received study treatment.
Vascular disorders Subdural hematoma	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Respiratory, thoracic and mediastinal disorders pneumonia	18.2% 2/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Musculoskeletal and connective tissue disorders femur fracture	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Blood and lymphatic system disorders thrombocytopenia	18.2% 2/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Infections and infestations cellulitis right forearm	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Infections and infestations urinary tract infection	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Blood and lymphatic system disorders cytopenia	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Blood and lymphatic system disorders febrile neutropenia	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Musculoskeletal and connective tissue disorders joint swelling	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Infections and infestations e. coli positive	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Reproductive system and breast disorders Ovarian abscess	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Nervous system disorders mental status change	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Cardiac disorders congestive heart failure	18.2% 2/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Nervous system disorders stroke	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Infections and infestations gram positive cocci	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Renal and urinary disorders renal failure	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Respiratory, thoracic and mediastinal disorders hypoxia	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Respiratory, thoracic and mediastinal disorders pleural effusion	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Gastrointestinal disorders cholecystitis	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Cardiac disorders pulmonary hypertension	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Cardiac disorders decreased ejection fraction	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.

Other adverse events

Other adverse events
Measure	All Groups n=11 participants at risk All patients who received study treatment.
Respiratory, thoracic and mediastinal disorders allergic rhinits	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Blood and lymphatic system disorders anemia	63.6% 7/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Blood and lymphatic system disorders leukopenia	36.4% 4/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Blood and lymphatic system disorders lymphopenia	45.5% 5/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Blood and lymphatic system disorders neutropenia	54.5% 6/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Blood and lymphatic system disorders splenomegaly	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Blood and lymphatic system disorders thrombocytopenia	81.8% 9/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Cardiac disorders Afibrilation with RVR	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Cardiac disorders Atrial Flutter with AV Block	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Cardiac disorders Ventricular Tachycardia	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Cardiac disorders Cardiomegaly	18.2% 2/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Cardiac disorders Hypertension	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Cardiac disorders Inferior Cardiac Infarct	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Cardiac disorders pericarditis	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Cardiac disorders elevated PTT	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
General disorders diaphoretic	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
General disorders fatigue	63.6% 7/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
General disorders fever	27.3% 3/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Psychiatric disorders insomnia	18.2% 2/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Injury, poisoning and procedural complications brusing	27.3% 3/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Skin and subcutaneous tissue disorders cracked lips	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Skin and subcutaneous tissue disorders dry skin	18.2% 2/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Injury, poisoning and procedural complications hernia	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Skin and subcutaneous tissue disorders itching	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Skin and subcutaneous tissue disorders lesions	36.4% 4/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Skin and subcutaneous tissue disorders rash: erythemia	27.3% 3/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Skin and subcutaneous tissue disorders ulceration	18.2% 2/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Vascular disorders hot flashes	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Gastrointestinal disorders vomiting	18.2% 2/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Gastrointestinal disorders abdominal distention	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Gastrointestinal disorders abdominal pain	45.5% 5/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Metabolism and nutrition disorders anorexia	36.4% 4/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Gastrointestinal disorders blood blisters in mouth	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Gastrointestinal disorders constipation	18.2% 2/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Gastrointestinal disorders diarrhea	27.3% 3/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Gastrointestinal disorders flatulence	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Gastrointestinal disorders heart burn	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Gastrointestinal disorders mouth sores	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Gastrointestinal disorders nausea	36.4% 4/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Gastrointestinal disorders oral thrush	18.2% 2/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Blood and lymphatic system disorders hematomas	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Blood and lymphatic system disorders petechia	36.4% 4/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Infections and infestations c. differential positive	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Infections and infestations cellulitis	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Infections and infestations eye infection	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Infections and infestations head cold	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Infections and infestations infections with unknown ANC	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Blood and lymphatic system disorders neutropenic fever	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Infections and infestations prostatitis	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Infections and infestations sepsis	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Infections and infestations sore throat	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Infections and infestations upper respiratory infection	18.2% 2/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Infections and infestations yeast infection	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
General disorders edema (bilateral lower extremity)	27.3% 3/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
General disorders pedal edema	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Investigations elevated alkaline phosphatase	27.3% 3/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Investigations elevated ALT	18.2% 2/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Investigations elevated amylase	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Investigations elevated AST	36.4% 4/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Metabolism and nutrition disorders elevated uric acid	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Investigations Hyperbilirubinemia	27.3% 3/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Metabolism and nutrition disorders hypercalcemia	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Metabolism and nutrition disorders hyperglycemia	63.6% 7/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Metabolism and nutrition disorders Hypoalbuminemia	54.5% 6/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Metabolism and nutrition disorders hypocalcemia	18.2% 2/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Metabolism and nutrition disorders hypoglycemia	27.3% 3/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Metabolism and nutrition disorders hyponatremia	18.2% 2/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Investigations increased creatinine	27.3% 3/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Metabolism and nutrition disorders hypokelmia	18.2% 2/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Musculoskeletal and connective tissue disorders bilateral leg weakness	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Musculoskeletal and connective tissue disorders fracture	18.2% 2/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Musculoskeletal and connective tissue disorders hand laceration	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Musculoskeletal and connective tissue disorders muscle cramps	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Musculoskeletal and connective tissue disorders muscle weakness	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Nervous system disorders confusion	18.2% 2/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Nervous system disorders dizziness	27.3% 3/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Nervous system disorders drowsiness	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Nervous system disorders hallucination	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Nervous system disorders neuropathy: cranial	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Nervous system disorders neuropathy: motor	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Nervous system disorders anxiety	18.2% 2/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Nervous system disorders syncope	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Eye disorders left eye redness	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Eye disorders eye scratch	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Musculoskeletal and connective tissue disorders back pain	36.4% 4/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
General disorders chest pain	27.3% 3/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Renal and urinary disorders dysuria	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Nervous system disorders headache	27.3% 3/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Musculoskeletal and connective tissue disorders joint pain	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Gastrointestinal disorders oral pain	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Musculoskeletal and connective tissue disorders right knee pain	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Gastrointestinal disorders throat pain	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
General disorders pain at port site	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Metabolism and nutrition disorders rib pain	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Respiratory, thoracic and mediastinal disorders atelectasis	18.2% 2/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Respiratory, thoracic and mediastinal disorders bronchitis	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Respiratory, thoracic and mediastinal disorders chest congestion	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Respiratory, thoracic and mediastinal disorders cough	45.5% 5/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Respiratory, thoracic and mediastinal disorders crackles in lungs	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Respiratory, thoracic and mediastinal disorders Dyspenia	27.3% 3/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Respiratory, thoracic and mediastinal disorders pleural effusion	27.3% 3/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Respiratory, thoracic and mediastinal disorders pneumonia	27.3% 3/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Respiratory, thoracic and mediastinal disorders pulmonary edema	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Respiratory, thoracic and mediastinal disorders wheezing	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Vascular disorders lower extremity phlebitis	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Vascular disorders superficial thrombosis	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Cardiac disorders pericardial thickening	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Infections and infestations urinary tract infection	18.2% 2/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Musculoskeletal and connective tissue disorders arthritis	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Musculoskeletal and connective tissue disorders bone pain	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Gastrointestinal disorders bleeding in mouth	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Skin and subcutaneous tissue disorders night sweats	9.1% 1/11 • Adverse events were collected after the administration of the study drug and followed until resolution.
Skin and subcutaneous tissue disorders erythematous	18.2% 2/11 • Adverse events were collected after the administration of the study drug and followed until resolution.

Additional Information

Dr. Paul Shami

Huntsman Cancer Institute

Phone: 801-585-0100

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place