Lenalidomide (Revlimid®, CC-5013) in Subjects With Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma

• Sponsor: Celgene Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00179673
• Collaborator: Prologue Research International (Industry)
• Enrollment: 43
• Locations: 15
• Arm: 1
• Duration (Months): 32
• Patients Per Site: 2.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Participants who qualify will receive lenalidomide daily on days 1-21 of every 28 day cycle. Treatment will continue for up to 52 weeks or until disease progression; participants who achieve a complete response (CR) will receive an additional 2 cycles of treatment prior to discontinuation. Participants will be followed for progression free survival following discontinuation from the treatment phase

Condition or Disease	Intervention/Treatment	Phase
Non-Hodgkins Lymphoma	Drug: Lenalidomide	Phase 2

Detailed Description

Participants who qualified for enrollment into the study entered the treatment phase and received single-agent lenalidomide 25 mg once daily on Days 1 to 21 of every 28-day cycle. The treatment phase began on Day 1 of Cycle 1. Study visits were scheduled to occur every 28 days to coincide with the beginning of a new cycle. The start date of a new cycle was delayed if adverse events (AEs) occurred, in which case the visit date for the start of the following cycle was scheduled 28 days after the actual start date of the delayed cycle. Efficacy and safety assessments, including complete blood counts (CBCs) were performed at least every 2 weeks during Cycles 1 to 4 of the treatment phase. Participants continued in the treatment phase of the study for up to 52 weeks or until disease progression developed, lenalidomide treatment was discontinued for any reason, or the study was terminated.

Study Design

• Study Type: Interventional
• Actual Enrollment: 43 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II, Multicenter, Single-Arm, Open-Label Study to Evaluate the Safety and Efficacy of Single-Agent Lenalidomide (Revlimid®, CC-5013) in Participants With Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma
• Study Start Date: Aug 1, 2005
• Actual Primary Completion Date: Apr 1, 2008
• Actual Study Completion Date: Apr 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lenalidomide Participants received single-agent lenalidomide 25 mg orally once daily on Days 1 to 21 of every 28-day cycle for up to 52 weeks or until disease progression developed, lenalidomide treatment was discontinued for any reason, or the study was terminated.	Drug: Lenalidomide; Lenalidomide 25 mg orally once daily on Days 1 to 21 of every 28-day cycle for up to 52 weeks or until disease progression developed; Other Names: CC-5013; Revlimid®

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Response [From enrollment through study completion. Median duration on study was 4.4 months with a maximum of 32 months]

   Response was defined as participants with a complete response (CR), unconfirmed complete response (Cru) or partial response (PR), assessed using the International Workshop Lymphoma Response Criteria (IWLRC) and based on best responses as determined by the investigator. CR: Complete disappearance of all detectable clinical and radiographic evidence of disease, disappearance of any disease-related symptoms, and normalization of biochemical abnormalities. Cru: Criteria for CR above but with 1 or more of the following: A residual lymph node mass > 1.5 cm in greatest transverse diameter that has regressed by more than 75% in the sum of the products of diameters (SPD) Indeterminate bone marrow (increased number or size of aggregates without cytologic or architectural atypia). PR: ≥ 50% decrease in SPD of the 6 largest dominant nodes or nodal masses. No increase in the size of other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD.

Secondary Outcome Measures

1. Percentage of Participants With Tumor Control [From enrollment through study completion. Median duration on study was 4.4 months with a maximum of 32 months]

   Tumor control was defined as participants with a complete response, unconfirmed complete response, partial response or stable disease (SD), assessed using the International Workshop Lymphoma Response Criteria (IWLRC) and based on best responses as determined by the investigator. SD was defined as a response less than a PR (see above) but not Progressive Disease (PD). PD was defined as ≥ 50 % increase from nadir in the SPD of any previously identified abnormal node for partial responders or non-responders. Appearance of any new lesion during or at the end of therapy.

2. The Duration of Response [From enrollment through study completion. Median duration on study was 4.4 months with a maximum of 32 months]

   The duration of response was calculated as the first response assessment demonstrating evidence of at least a partial response to the first documentation of progressive disease (as determined by computed tomography scan) or death due to NHL, whichever occurred first. For participants without documentation of progression, the duration of response was censored at the last date of tumor assessment indicating no progression. Median was based on the Kaplan-Meier estimate.

3. Progression Free Survival (PFS) [From enrollment through study completion. Median duration on study was 4.4 months with a maximum of 32 months]

   Progression-free survival was defined as the time from the start of study drug therapy to the first observation of disease progression or death due to any cause, whichever came first. Participants who withdrew for any reason or received another NHL therapy including stem cell transplantation without documented progressive disease were censored on the date of their last adequate response assessment indicating no progression (or last adequate assessment prior to receiving other NHL therapy). Participants who were still active without progressive disease at the time of the data cut-off date were censored on the date of their last adequate response assessment.

4. Number of Participants With Adverse Events (AEs) [From the start of study drug through 30 days after the last dose of study drug. Maximum time on study drug was 13.8 months.]

   The Investigator determined the relationship between the administration of study drug and the occurrence of an AE as suspected if the temporal relationship of the adverse event to study drug administration made a causal relationship possible, and other drugs, therapeutic interventions, or underlying conditions did not provide a sufficient explanation for the observed event. The Investigator graded the severity of AEs according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria and the following scale: Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life threatening Grade 5 = Death A Serious AE is defined as any AE which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or constitutes an important medical event.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Understand and voluntarily sign an informed consent form.

2. Age greater than or equal to 18 years at the time of signing the informed consent form

3. Able to adhere to the study visit schedule and other protocol requirements

4. Biopsy-proven non-Hodgkin's lymphoma (NHL)

5. Indolent lymphoma the following histologies are acceptable:

6. Follicular center lymphoma, grades 1, 2,

7. Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type,

8. Nodal marginal zone B-cell lymphoma

9. Splenic marginal zone B-cell lymphoma,

10. Small lymphocytic lymphoma,

11. Lymphoplasmacytoid lymphoma

12. Relapsed or refractory to previous therapy for lymphoma. Participants must have received at least one prior treatment regimen such as radiation, immunotherapy, chemotherapy, OR radioimmunotherapy, and be ineligible or unwilling to undergo an autologous stem cell transplant. There is no limit on the number of prior therapies

13. Participants must have measurable disease on cross sectional imaging that is at least 2 cm in the longest diameter

14. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2

15. Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception or to practice complete abstinence from heterosexual intercourse during the following periods 1) for at least 28 days before starting study drug; 2) while participating in the study; and 3) for at least 28 days after discontinuation from the study. The two methods of reliable contraception must include one highly effective method (i.e. intrauterine device (IUD), hormonal [birth control pills, injections, or implants], tubal ligation, partner's vasectomy) and one additional effective (barrier) method (i.e. latex condom, diaphragm, cervical cap). FCBP must be referred to a qualified provider of contraceptive methods if needed.

Exclusion Criteria:

1. Any of the following laboratory abnormalities

2. Absolute neutrophil count (ANC) <1,500 cells/mm^{3 (1.5 x 10}9/L)

3. Platelet count <100,000/mm^{3 (100 x 10}9/L)

4. Serum creatinine >2.5 mg/dL (221 mmol/L)

5. Serum glutamic-oxaloacetic transaminase/ aspartate aminotransferase (SGOT/AST) or serum glutamic:pyruvic transaminase/alanine aminotransferase (SGPT/ALT) >5.0 x upper limit of normal (ULN)

6. Serum total bilirubin >2.0 mg/dL (34 mmol/L)

7. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.

8. All participants with Central Nervous System (CNS) disease with the exception of those subjects whose CNS disease has been treated with chemotherapy, radiotherapy or surgery and remains asymptomatic, with no active CNS disease, as shown by lumbar puncture, Computed Tomography or Magnetic resonance imaging (CT scan or MRI), for at least 6 months.

9. Prior history of malignancies other than NHL (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless the subject has been free of the disease for > or equal to 1 year.

10. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.

11. Known positive for Human Immunodeficiency Virus (HIV).

12. Pregnant or lactating females.

13. Prior ≥ grade 3 (National Cancer Institute-Common Terminology Criteria for Adverse Events [NCI CTCAE]) allergic reaction/hypersensitivity to thalidomide.

14. Prior ≥ grade 3 rash or any desquamating (blistering) rash while taking thalidomide.

15. Prior use of lenalidomide.

16. Use of any standard or experimental anti-cancer drug therapy within 28 days of day 1 of study drug therapy.

17. Known active Hepatitis C.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Scottsdale	Scottsdale	Arizona	United States	85259
2	Alta Bates Cancer Center	Berkeley	California	United States	94704
3	Pacific Coast Hematology/Oncology Medical Group, Onc.	Fountain Valley	California	United States	92708
4	Rush University Medical Center	Chicago	Illinois	United States	60612
5	Harvard University	Boston	Massachusetts	United States	02115
6	Mayo Clinic	Rochester	Minnesota	United States	55905
7	University of Nebraska	Omaha	Nebraska	United States	68198-6805
8	New York Medical Center, MBCCOP	Bronx	New York	United States	10466
9	Signal Point Hematology/Oncology	Middletown	Ohio	United States	45042
10	Swedish Cancer Institute	Seattle	Washington	United States	98104
11	Gunderson Clinic, Ltd.	La Crosse	Wisconsin	United States	54601
12	BC Community Oncology Trialist	Burnaby	British Columbia	Canada	V5H 4K7
13	BC Community Oncology	North Vancouver	British Columbia	Canada	V7L 2P9
14	London Regional Cancer Program	London	Ontario	Canada	N6A 5W9
15	University of Saskatchewan	Saskatoon	Saskatchewan	Canada	S7N 4H4

Sponsors and Collaborators

• Celgene Corporation
• Prologue Research International

Investigators

• Study Director: Robert Knight, MD, Celgene

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Celgene Corporation
• ClinicalTrials.gov Identifier: NCT00179673
• Other Study ID Numbers: CC-5013-NHL-001
• First Posted: Sep 16, 2005
• Last Update Posted: Nov 28, 2013
• Last Verified: Nov 1, 2013

• Keywords provided by Celgene Corporation: NHL; CC5013; Non-Hodgkins Lymphoma; revlimid; cc-5013; celgene
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lenalidomide

Study Results

Participant Flow

Arm/Group Title	Lenalidomide
Arm/Group Description	Participants received single-agent lenalidomide 25 mg orally once daily on Days 1 to 21 of every 28-day cycle for up to 52 weeks or until disease progression developed, lenalidomide treatment was discontinued for any reason, or the study was terminated.
Period Title: Overall Study
STARTED	43
Received Study Drug	43
COMPLETED	0
NOT COMPLETED	43

Baseline Characteristics

Arm/Group Title	Lenalidomide
Arm/Group Description	Participants received single-agent lenalidomide 25 mg orally once daily on Days 1 to 21 of every 28-day cycle for up to 52 weeks or until disease progression developed, lenalidomide treatment was discontinued for any reason, or the study was terminated.
Overall Participants	43
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.6 (10.95)
Age, Customized (participants) [Number]
<65 years	24 55.8%
65 - 75	10 23.3%
>75 years	9 20.9%
Sex: Female, Male (Count of Participants)
Female	17 39.5%
Male	26 60.5%
Race/Ethnicity, Customized (participants) [Number]
White	37 86%
Black	4 9.3%
Hispanic	0 0%
Asian/Pacific Islander	1 2.3%
American Indian/Alaska Native	0 0%
Other = Unspecified	1 2.3%
NHL Duration (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	5.6 (4.38)
Non-Hodgkin's Lymphoma (NHL) Histology (participants) [Number]
Follicular lymphoma grade 1 or 2	22 51.2%
Small Lymphocytic lymphoma	18 41.9%
Nodal marginal-zone B-cell lymphoma	2 4.7%
Extranodal marginal-zone B-cell type (MALT)	1 2.3%
Non-Hodgkin's Lymphoma (NHL)-Stage (participants) [Number]
Stage I	1 2.3%
Stage II	11 25.6%
Stage III	6 14%
Stage IV	25 58.1%
International Prognostic Index (IPI)] (participants) [Number]
Low (0 to 1)	14 32.6%
Low/Intermediate (2)	15 34.9%
High/Intermediate (3)	6 14%
High (4 to 5)	8 18.6%
Eastern Cooperative Oncology Group (ECOG) performance status (participants) [Number]
0 = fully active, no restrictions;	27 62.8%
1 = restricted but ambulatory and capable of light	12 27.9%
2 = ambulatory and capable of self care but unable	4 9.3%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Response
Description	Response was defined as participants with a complete response (CR), unconfirmed complete response (Cru) or partial response (PR), assessed using the International Workshop Lymphoma Response Criteria (IWLRC) and based on best responses as determined by the investigator. CR: Complete disappearance of all detectable clinical and radiographic evidence of disease, disappearance of any disease-related symptoms, and normalization of biochemical abnormalities. Cru: Criteria for CR above but with 1 or more of the following: A residual lymph node mass > 1.5 cm in greatest transverse diameter that has regressed by more than 75% in the sum of the products of diameters (SPD) Indeterminate bone marrow (increased number or size of aggregates without cytologic or architectural atypia). PR: ≥ 50% decrease in SPD of the 6 largest dominant nodes or nodal masses. No increase in the size of other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD.
Time Frame	From enrollment through study completion. Median duration on study was 4.4 months with a maximum of 32 months

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population, which included all enrolled patients who received at least 1 dose of study drug. Patients who dropped out without having a response assessment or who had a response after they had received other anti-cancer treatments were considered non-responders.

Arm/Group Title	Lenalidomide
Arm/Group Description	Participants received single-agent lenalidomide 25 mg orally once daily on Days 1 to 21 of every 28-day cycle for up to 52 weeks or until disease progression developed, lenalidomide treatment was discontinued for any reason, or the study was terminated.
Measure Participants	43
Number (95% Confidence Interval) [percentage of participants]	23.3 54.2%

2. Secondary Outcome

Title	Percentage of Participants With Tumor Control
Description	Tumor control was defined as participants with a complete response, unconfirmed complete response, partial response or stable disease (SD), assessed using the International Workshop Lymphoma Response Criteria (IWLRC) and based on best responses as determined by the investigator. SD was defined as a response less than a PR (see above) but not Progressive Disease (PD). PD was defined as ≥ 50 % increase from nadir in the SPD of any previously identified abnormal node for partial responders or non-responders. Appearance of any new lesion during or at the end of therapy.
Time Frame	From enrollment through study completion. Median duration on study was 4.4 months with a maximum of 32 months

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population. Patients who dropped out without having a response assessment or who had a response after they had received other anti-cancer treatments were considered non-responders

Arm/Group Title	Lenalidomide
Arm/Group Description	Participants received single-agent lenalidomide 25 mg orally once daily on Days 1 to 21 of every 28-day cycle for up to 52 weeks or until disease progression developed, lenalidomide treatment was discontinued for any reason, or the study was terminated.
Measure Participants	43
Number (95% Confidence Interval) [percentage of participants]	60.5 140.7%

3. Secondary Outcome

Title	The Duration of Response
Description	The duration of response was calculated as the first response assessment demonstrating evidence of at least a partial response to the first documentation of progressive disease (as determined by computed tomography scan) or death due to NHL, whichever occurred first. For participants without documentation of progression, the duration of response was censored at the last date of tumor assessment indicating no progression. Median was based on the Kaplan-Meier estimate.
Time Frame	From enrollment through study completion. Median duration on study was 4.4 months with a maximum of 32 months

Outcome Measure Data

Analysis Population Description

Includes participants with a response to treatment

Arm/Group Title	Lenalidomide
Arm/Group Description	Participants received single-agent lenalidomide 25 mg orally once daily on Days 1 to 21 of every 28-day cycle for up to 52 weeks or until disease progression developed, lenalidomide treatment was discontinued for any reason, or the study was terminated.
Measure Participants	10
Median (95% Confidence Interval) [months]	NA

4. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	Progression-free survival was defined as the time from the start of study drug therapy to the first observation of disease progression or death due to any cause, whichever came first. Participants who withdrew for any reason or received another NHL therapy including stem cell transplantation without documented progressive disease were censored on the date of their last adequate response assessment indicating no progression (or last adequate assessment prior to receiving other NHL therapy). Participants who were still active without progressive disease at the time of the data cut-off date were censored on the date of their last adequate response assessment.
Time Frame	From enrollment through study completion. Median duration on study was 4.4 months with a maximum of 32 months

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	Lenalidomide
Arm/Group Description	Participants received single-agent lenalidomide 25 mg orally once daily on Days 1 to 21 of every 28-day cycle for up to 52 weeks or until disease progression developed, lenalidomide treatment was discontinued for any reason, or the study was terminated.
Measure Participants	43
Median (95% Confidence Interval) [months]	4.4

5. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs)
Description	The Investigator determined the relationship between the administration of study drug and the occurrence of an AE as suspected if the temporal relationship of the adverse event to study drug administration made a causal relationship possible, and other drugs, therapeutic interventions, or underlying conditions did not provide a sufficient explanation for the observed event. The Investigator graded the severity of AEs according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria and the following scale: Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life threatening Grade 5 = Death A Serious AE is defined as any AE which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or constitutes an important medical event.
Time Frame	From the start of study drug through 30 days after the last dose of study drug. Maximum time on study drug was 13.8 months.

Outcome Measure Data

Analysis Population Description

Safety Population, which includes all participants who received at least one dose of study drug.

Arm/Group Title	Lenalidomide
Arm/Group Description	Participants received single-agent lenalidomide 25 mg orally once daily on Days 1 to 21 of every 28-day cycle for up to 52 weeks or until disease progression developed, lenalidomide treatment was discontinued for any reason, or the study was terminated.
Measure Participants	43
At least one Adverse Event (AE)	42 97.7%
≥ 1 AE related to study drug	37 86%
Grade (GR) 3-5 AE	27 62.8%
Grade 3-5 AE related to study drug	24 55.8%
Serious adverse event (SAE)	18 41.9%
SAE related to study drug	10 23.3%
AE leading to discontinuation of study drug	9 20.9%
Related AE leading to study drug discontinuation	5 11.6%
AE leading to dose reduction or interruption	27 62.8%

Adverse Events

Time Frame	From the start of study drug through 30 days after the last dose of study drug. Maximum time on study drug was 13.8 months
Arm/Group Title	Lenalidomide
Arm/Group Description	Participants received single-agent lenalidomide 25 mg orally once daily on Days 1 to 21 of every 28-day cycle for up to 52 weeks or until disease progression developed, lenalidomide treatment was discontinued for any reason, or the study was terminated.
All Cause Mortality
	Lenalidomide
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Lenalidomide
	Affected / at Risk (%)	# Events
Total	10/43 (23.3%)
Blood and lymphatic system disorders
Anemia Not Otherwise Specified (NOS)	1/43 (2.3%)
Lymph Node Pain	1/43 (2.3%)
Febrile Neutropenia	1/43 (2.3%)
Pancytopenia	1/43 (2.3%)
Thrombocytopenia	1/43 (2.3%)
Gastrointestinal disorders
Abdominal Pain NOS	2/43 (4.7%)
Constipation	1/43 (2.3%)
Diarrhoea NOS	1/43 (2.3%)
General disorders
Pyrexia	1/43 (2.3%)
Infections and infestations
Sepsis NOS	1/43 (2.3%)
Nervous system disorders
Transient Ischaemic Attack	1/43 (2.3%)
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism	1/43 (2.3%)
Other (Not Including Serious) Adverse Events
	Lenalidomide
	Affected / at Risk (%)	# Events
Total	41/43 (95.3%)
Blood and lymphatic system disorders
Neutropenia	19/43 (44.2%)
Thrombocytopenia	15/43 (34.9%)
Leukopenia NOS	10/43 (23.3%)
Anaemia NOS	7/43 (16.3%)
Gastrointestinal disorders
Constipation	13/43 (30.2%)
Diarrhoea NOS	13/43 (30.2%)
Nausea	8/43 (18.6%)
Abdominal Pain NOS	5/43 (11.6%)
General disorders
Fatigue	20/43 (46.5%)
Oedema Peripheral	4/43 (9.3%)
Pain NOS	4/43 (9.3%)
Pyrexia	4/43 (9.3%)
Investigations
Haemoglobin Decreased	8/43 (18.6%)
Neutrophil Count Decreased	8/43 (18.6%)
Alanine Aminotransferase Increased	5/43 (11.6%)
Blood Alkaline Phosphatase NOS Increased	4/43 (9.3%)
White Blood Cell Count Decreased	4/43 (9.3%)
Aspartate Aminotransferase Increased	3/43 (7%)
Platelet Count Decreased	3/43 (7%)
Metabolism and nutrition disorders
Hyperglycaemia NOS	5/43 (11.6%)
Hyperkalemia	3/43 (7%)
Musculoskeletal and connective tissue disorders
Arthralgia	7/43 (16.3%)
Muscle Cramp	5/43 (11.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour Flare	4/43 (9.3%)
Nervous system disorders
Headache	4/43 (9.3%)
Hypoaesthesia	3/43 (7%)
Psychiatric disorders
Insomnia	6/43 (14%)
Respiratory, thoracic and mediastinal disorders
Cough	7/43 (16.3%)
Pharyngitis	5/43 (11.6%)
Skin and subcutaneous tissue disorders
Rash NOS	10/43 (23.3%)
Pruritus	5/43 (11.6%)
Night Sweats	3/43 (7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The investigator shall have the right to publish and/or present study data provided that the investigator shall (i) furnish the sponsor a copy of any proposed publication or presentation generally thirty (60) days in advance of the submission, (ii) delete any confidential information of the sponsor, and (iii) delay submission for generally up to ninety (90) days to permit the preparation and filing of intellectual property applications or until sponsor gives its consent in a timely manner.