A Phase II Trial of Avelumab in Patients With Recurrent or Progressive Osteosarcoma

• Sponsor: St. Jude Children's Research Hospital (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03006848
• Collaborator: National Cancer Institute (NCI) (NIH), Pfizer (Industry), Gateway for Cancer Research (Other)
• Enrollment: 19
• Locations: 4
• Arm: 1
• Anticipated Duration (Months): 71.5
• Patients Per Site: 4.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This clinical trial seeks to determine if avelumab will be effective in facilitating removal of all gross tumor in the event of a relapse of osteosarcoma in pediatric patients. Avelumab will be evaluated using dosing that has previously been determined in adult studies.

Primary Objectives:

• To estimate the response rate to 4 cycles of avelumab in patients with recurrent or progressive osteosarcoma.

• To estimate the 16-week progression free survival of patients with recurrent or progressive osteosarcoma after treatment with avelumab.

Secondary Objective:

• To describe the toxicities associated with the administration of avelumab in patients with recurrent or progressive osteosarcoma.

• To assess the quality of life of patients with recurrent or progressive osteosarcoma undergoing treatment with avelumab, and to explore relationships between clinical factors and patient-reported health-related quality of life (HRQOL) outcomes.

Exploratory Objectives:

• To explore factors associated with response in patients treated with avelumab after recurrent or progressive osteosarcoma (e.g. tumor PD-L1 expression).

• To measure parameters of immune activation including subsets of peripheral blood mononuclear cells (PBMCs) and serum markers of immune activation.

• To evaluate the role of T-cells in immune checkpoint blockade via measures of cell proliferation, co-inhibitory receptor expression on CD8 T cells, T cell repertoire, and epigenetic programming.

Condition or Disease	Intervention/Treatment	Phase
Osteosarcoma	Drug: Avelumab; Other: Questionnaires	Phase 2

Detailed Description

This is a Phase 2 study using a traditional Simon two-stage design. Patients 12 years or greater with recurrent/refractory osteosarcoma will be administered avelumab at a dose of 10 mg/kg intravenously (IV) over 60 minutes on days 1 and 15 of each cycle, with a cycle lasting 28 days.

Patients will receive avelumab every 2 weeks in cycles of 28 days for up to 24 months, or 26 cycles. Progression free survival and response to therapy after 4 cycles of treatment will be assessed. In addition, the toxicity profile of avelumab in this population will be closely monitored.

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Avelumab, A Fully Human Antibody That Targets Cells Expressing PD-L1, in Patients With Recurrent or Progressive Osteosarcoma
• Actual Study Start Date: Feb 16, 2017
• Actual Primary Completion Date: Mar 18, 2020
• Anticipated Study Completion Date: Jan 31, 2023

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Avelumab All participants with recurrent/refractory osteosarcoma who consent to the study. Interventions: Avelumab and quality of life questionnaires.

Drug: Avelumab; Patients will be administered avelumab at a dose of 10 mg/kg intravenously (IV) over 60 minutes on days 1 and 15 of each cycle, with a cycle lasting 28 days. Patients will receive avelumab every 2 weeks in cycles of 28 days for up to 24 months, or 26 cycles.; Other Names: MSB0010718C anti-PD-L1 ; Other: Questionnaires; To assess quality of life, patients will complete questionnaires at four time points.; Other Names: PROMIS Pediatric Profile PROMIS Adult Profile

Outcome Measures

Primary Outcome Measures

1. Response Rate [At the end of 4 cycles of avelumab (approximately 4 months)]

   The study is designed by treating RECIST response [complete response + partial response (CR+PR)] after 4-cycle treatment of avelumab and the 16-week progression-free survival (PFS) as dual binary endpoints. Patients who fail to be evaluated at the end of the 4-cycle will be counted as failure.

2. Progression-free Survival [At the end of 4 cycles of avelumab (approximately 4 months)]

   The study is designed by treating RECIST response [complete response + partial response (CR+PR)] after 4-cycle treatment of avelumab and the 16-week progression-free survival (PFS) as dual binary endpoints. Patients who fail to be evaluated at the end of the 4-cycle will be counted as failure.

Secondary Outcome Measures

1. Target Toxicities [At the end of treatment (up to 2 years after enrollment of last participant)]

   Target toxicities for avelumab treatment are defined as any grade 3-5 dyspnea, infusion-related reactions, or immune related adverse events at least possibly attributable to the agent observed anytime during the 26-cycle treatment period that a patient is on study (including the period between off treatment and off study).

Other Outcome Measures

1. Factors Associated With Response [Following completion of therapy for last participant (up to 2 years after enrollment)]

   Logistic regression analysis will be conducted to explore factors which may associate with response.

2. Change in Parameters of Immune Activation [Baseline prior to start of therapy and following 2 cycles of therapy (up to 8 weeks after last enrollment)]

   Descriptive statistics will be provided.

3. Change in Cell Proliferation [Baseline prior to start of therapy and after completion of therapy (approximately 2 years after last participant enrollment).]

   Descriptive statistics will be provided.

4. Change in Co-inhibitory Receptor Expression on CD8 T Cells [Baseline prior to start of therapy and after completion of therapy (approximately 2 years after last participant enrollment).]

   Descriptive statistics will be provided.

5. Change in Quality of Life [From baseline prior to start of treatment through the end of avelumab therapy (up to approximately 2 years)]

   Participants will self-report their quality of life through PROMIS questionnaires, either the Pediatric Profile (ages 8 to 17 years) or the Adult Profile (age 18 years or older). The change in age-normed T-scores will be reported. Mixed effect models will be performed to assess changes in quality of life over time.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 49 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must be > 12 years of age but < 50 years of age at the time of enrollment.

• Patients must have histologic verification of osteosarcoma at initial diagnosis or relapse.

• Patients must have had evidence of having relapsed, progressed or become refractory to conventional therapy.

• Patients must have measurable disease, documented by clinical, radiographic or histologic criteria. Disease must be bi-dimensionally measurable by computed tomography (CT) or magnetic resonance imaging (MRI).

• Patients must have a performance status of ≥ 50 using the Karnofsky scale for patients

16 years of age and the Lansky scale for patients ≤ 16 years of age.

• Patients must have a life expectancy of ≥ 6 weeks.

• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.

1. Myelosuppressive chemotherapy: must not have received within 3 weeks of entry onto this study.

2. Biologic (anti-neoplastic agent): at least 7 days since the completion of therapy with a biologic agent.

3. Immunotherapies: at least 42 days must have elapsed since a prior therapy that included a monoclonal antibody or any other type of immunotherapy (e.g. chimeric antigen receptor (CAR) T cell therapy).

4. Radiation therapy (RT): ≥ 2 weeks for local palliative RT (small port); ≥ 6 months must have elapsed if prior craniospinal RT or if ≥ 50% radiation of the pelvis; ≥ 6 weeks must have elapsed if other substantial bone marrow (BM) radiation.

• Organ Function Requirements:

1. Adequate bone marrow function defined as:

• Peripheral absolute neutrophil count (ANC) ≥ 1500/mm3

• Platelet count ≥ 100,000/mm3 (transfusion independent)

• Hemoglobin ≥ 9.0 g/dL (may receive RBC transfusions)

1. Adequate renal function defined as:

• Creatinine clearance or radioisotope GFR ≥70 mL/min/1.73m2 OR

• Serum creatinine based on age/gender as follows: (threshold creatinine values were derived from the Schwartz formula for estimating GFR).

• Age is: 12 to <13 years, then maximum creatinine is 1.2 mg/DL for male and female.

• Age is: 13 to <16 years, then maximum creatinine is 1.5 mg/DL for male and 1.4 mg/DL for female.

• Age is: ≥16 years, then maximum creatinine is 1.7 mg/DL for male and 1.4 mg/DL for female.

1. Adequate liver function defined as:

• Total Bilirubin ≤ 1.5x the institutional upper limit of normal (IULN) for age

• ALT (SGPT) and AST (SGOT) < 2.5 x IULN for age (or < 5 x IULN for patients with documented metastatic disease to the liver)

• Serum albumin > 2 g/dL

1. Serum lipase ≤ upper limit of normal (IULN).

2. Patients must have documented pulse oximetry ≥ 92% on room air.

• Female patients of childbearing potential must have a negative serum or urine pregnancy test within 7 days of enrollment.

• Male or female patients who are sexually active and of reproductive potential must agree to use an effective contraceptive method throughout the study and for at least 60 days after last avelumab treatment administration. Abstinence is an acceptable form of contraception.

• Patients must not currently be using other investigational agents.

• Patients must not currently be using other anti-cancer agent.

• Patients must be able to comply with the safety monitoring of the study in the opinion of the investigator.

• Written, informed consent and assent following Institutional Review Board, NCI, FDA and OHRP guidelines.

Exclusion Criteria:

• Central nervous system (CNS) metastases.

• Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).

• Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.

• Active infection requiring systemic therapy.

• Known history of testing positive for HIV or known acquired immunodeficiency syndrome.

• Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive).

• Patient who has received vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines.

• Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3).

• Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II, see Appendix II), or serious cardiac arrhythmia requiring medication.

• Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade > 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable

• Other severe acute or chronic medical conditions including colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

• Patients with active diarrhea > CTCAE v4.03 Grade 2.

• Patients who have previously received a prior organ transplantation, including allogeneic stem cell transplantation.

• Female patients who are pregnant or actively breastfeeding.

• Patients who have previously received anti-PD1 or anti-PD-L1 therapy. Patients who have previously received anti-CTLA-4 therapy (e.g. ipilimumab) are eligible for study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
2	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
3	St Jude Children's Research Hospital	Memphis	Tennessee	United States	38105
4	Texas Children's Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• St. Jude Children's Research Hospital
• National Cancer Institute (NCI)
• Pfizer
• Gateway for Cancer Research

Investigators

• Principal Investigator: Michael W. Bishop, MD, MS, St. Jude Children's Research Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 26, 2019

More Information

Additional Information:

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

Publications

None provided.

• Responsible Party: St. Jude Children's Research Hospital
• ClinicalTrials.gov Identifier: NCT03006848
• Other Study ID Numbers: OSTPDL1; NCI-2016-02036; Pfizer W1211733 (OSTPDL1); Gateway RESAG
• First Posted: Dec 30, 2016
• Last Update Posted: Aug 23, 2022
• Last Verified: Aug 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by St. Jude Children's Research Hospital: Osteosarcoma; PD-L1; Immunotherapy
• Additional relevant MeSH terms: Osteosarcoma; Avelumab

Study Results

Participant Flow

Recruitment Details	A total of 19 patients were enrolled on the study from February 2017 to April 2021
Pre-assignment Detail	18 out of 19 enrolled patients received treatment. The patient who did not receive treatment was found to be ineligible and thus was a screen failure.

Arm/Group Title	Avelumab
Arm/Group Description	All participants with recurrent/refractory osteosarcoma who consent to the study. Interventions: Avelumab and quality of life questionnaires. Avelumab: Patients will be administered avelumab at a dose of 10 mg/kg intravenously (IV) over 60 minutes on days 1 and 15 of each cycle, with a cycle lasting 28 days. Patients will receive avelumab every 2 weeks in cycles of 28 days for up to 24 months, or 26 cycles. Questionnaires: To assess quality of life, patients will complete questionnaires at four time points.
Period Title: Overall Study
STARTED	18
COMPLETED	0
NOT COMPLETED	18

Baseline Characteristics

Arm/Group Title	Avelumab
Arm/Group Description	All participants with recurrent/refractory osteosarcoma who consent to the study. Interventions: Avelumab and quality of life questionnaires. Avelumab: Patients will be administered avelumab at a dose of 10 mg/kg intravenously (IV) over 60 minutes on days 1 and 15 of each cycle, with a cycle lasting 28 days. Patients will receive avelumab every 2 weeks in cycles of 28 days for up to 24 months, or 26 cycles. Questionnaires: To assess quality of life, patients will complete questionnaires at four time points.
Overall Participants	18
Overall years	18
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	17.0 (3.3)
Sex: Female, Male (Count of Participants)
Female	6 33.3%
Male	12 66.7%
Race/Ethnicity, Customized (Count of Participants)
White	14 77.8%
Black	2 11.1%
Declined Respond	1 5.6%
Unknown	1 5.6%
Region of Enrollment (Count of Participants)
St. Jude Children's Research Hospital	14 77.8%
Memorial Sloan-Kettering Cancer Center	2 11.1%
Children's Hospital of Los Angeles	1 5.6%
Texas Children's Research Hospital	1 5.6%
Disease Status at time of enrollment (Count of Participants)
Progressive Disease	13 72.2%
Recurrent Disease	5 27.8%

Outcome Measures

1. Primary Outcome

Title	Response Rate
Description	The study is designed by treating RECIST response [complete response + partial response (CR+PR)] after 4-cycle treatment of avelumab and the 16-week progression-free survival (PFS) as dual binary endpoints. Patients who fail to be evaluated at the end of the 4-cycle will be counted as failure.
Time Frame	At the end of 4 cycles of avelumab (approximately 4 months)

Outcome Measure Data

Analysis Population Description

RECIST response [complete response + partial response (CR+PR)]

Arm/Group Title	Avelumab
Arm/Group Description	All participants with recurrent/refractory osteosarcoma who consent to the study. Interventions: Avelumab and quality of life questionnaires. Avelumab: Patients will be administered avelumab at a dose of 10 mg/kg intravenously (IV) over 60 minutes on days 1 and 15 of each cycle, with a cycle lasting 28 days. Patients will receive avelumab every 2 weeks in cycles of 28 days for up to 24 months, or 26 cycles. Questionnaires: To assess quality of life, patients will complete questionnaires at four time points.
Measure Participants	18
Number (95% Confidence Interval) [percentage of participants]	0 0%

2. Primary Outcome

Title	Progression-free Survival
Description	The study is designed by treating RECIST response [complete response + partial response (CR+PR)] after 4-cycle treatment of avelumab and the 16-week progression-free survival (PFS) as dual binary endpoints. Patients who fail to be evaluated at the end of the 4-cycle will be counted as failure.
Time Frame	At the end of 4 cycles of avelumab (approximately 4 months)

Outcome Measure Data

Analysis Population Description

Of the 18 eligible patients who received treatment, 17 patients had disease progression while on study and one patient died off study.

Arm/Group Title	Progression-free Survival
Arm/Group Description	The study is designed by treating RECIST response [complete response + partial response (CR+PR)] after 4-cycle treatment of avelumab and the 16-week progression-free survival (PFS) as dual binary endpoints. Patients who fail to be evaluated at the end of the 4-cycle will be counted as failure.
Measure Participants	18
Median (95% Confidence Interval) [percentage of weeks]	8.0

3. Secondary Outcome

Title	Target Toxicities
Description	Target toxicities for avelumab treatment are defined as any grade 3-5 dyspnea, infusion-related reactions, or immune related adverse events at least possibly attributable to the agent observed anytime during the 26-cycle treatment period that a patient is on study (including the period between off treatment and off study).
Time Frame	At the end of treatment (up to 2 years after enrollment of last participant)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Target Toxicities
Arm/Group Description	Target toxicities for avelumab treatment are defined as any grade 3-5 dyspnea, infusion-related reactions, or immune related adverse events at least possibly attributable to the agent observed anytime during the 26-cycle treatment period that a patient is on study (including the period between off treatment and off study).
Measure Participants	18
Dyspnea	2 11.1%
Infection and infestations	1 5.6%
Metabolism and nutrition disorders	2 11.1%
Blood and lymphatic system disorders	1 5.6%
Cardiac disorders	1 5.6%
Investigations	2 11.1%

4. Other Pre-specified Outcome

Title	Factors Associated With Response
Description	Logistic regression analysis will be conducted to explore factors which may associate with response.
Time Frame	Following completion of therapy for last participant (up to 2 years after enrollment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Factors Associated With Response
Arm/Group Description	Logistic regression analysis will be conducted to explore factors which may associate with response.
Measure Participants	0

5. Other Pre-specified Outcome

Title	Change in Parameters of Immune Activation
Description	Descriptive statistics will be provided.
Time Frame	Baseline prior to start of therapy and following 2 cycles of therapy (up to 8 weeks after last enrollment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Change in Parameters of Immune Activation
Arm/Group Description	Descriptive statistics will be provided.
Measure Participants	0

6. Other Pre-specified Outcome

Title	Change in Cell Proliferation
Description	Descriptive statistics will be provided.
Time Frame	Baseline prior to start of therapy and after completion of therapy (approximately 2 years after last participant enrollment).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Change in Cell Proliferation
Arm/Group Description	Descriptive statistics will be provided.
Measure Participants	0

7. Other Pre-specified Outcome

Title	Change in Co-inhibitory Receptor Expression on CD8 T Cells
Description	Descriptive statistics will be provided.
Time Frame	Baseline prior to start of therapy and after completion of therapy (approximately 2 years after last participant enrollment).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Change in Co-inhibitory Receptor Expression on CD8 T Cells
Arm/Group Description	Descriptive statistics will be provided.
Measure Participants	0

8. Other Pre-specified Outcome

Title	Change in Quality of Life
Description	Participants will self-report their quality of life through PROMIS questionnaires, either the Pediatric Profile (ages 8 to 17 years) or the Adult Profile (age 18 years or older). The change in age-normed T-scores will be reported. Mixed effect models will be performed to assess changes in quality of life over time.
Time Frame	From baseline prior to start of treatment through the end of avelumab therapy (up to approximately 2 years)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Change in Quality of Life
Arm/Group Description	Participants will self-report their quality of life through PROMIS questionnaires, either the Pediatric Profile (ages 8 to 17 years) or the Adult Profile (age 18 years or older). The change in age-normed T-scores will be reported. Mixed effect models will be performed to assess changes in quality of life over time.
Measure Participants	0

Adverse Events

Time Frame	Acute adverse events were collected from study enrollment up to 4 weeks after completion of chemotherapy/radiation therapy, whichever came last. Long term toxicity was captured at every visit up to 5 years from study enrollment.
Adverse Event Reporting Description	[Not specified]
Arm/Group Title	Avelumab
Arm/Group Description	[Not specified]
All Cause Mortality
	Avelumab
	Affected / at Risk (%)	# Events
Total	3/18 (16.7%)
Serious Adverse Events
	Avelumab
	Affected / at Risk (%)	# Events
Total	7/18 (38.9%)
Cardiac disorders
Cardiac disorders	1/18 (5.6%)	1
Gastrointestinal disorders
Gastrointestinal disorders	1/18 (5.6%)	1
Investigations
Investigations	1/18 (5.6%)	1
Investigations	1/18 (5.6%)	1
Metabolism and nutrition disorders
Metabolism and nutrition disorders	1/18 (5.6%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified	1/18 (5.6%)	1
Nervous system disorders
Nervous system disorders	1/18 (5.6%)	1
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders	2/18 (11.1%)	2
Respiratory, thoracic and mediastinal disorders	1/18 (5.6%)	1
Infections and infestations	1/18 (5.6%)	1
Vascular disorders
Blood and lymphatic system disorders	1/18 (5.6%)	1
Other (Not Including Serious) Adverse Events
	Avelumab
	Affected / at Risk (%)	# Events
Total	15/18 (83.3%)
Blood and lymphatic system disorders
Blood and lymphatic system disorders	1/18 (5.6%)	1
Blood and lymphatic system disorders	1/18 (5.6%)	2
Cardiac disorders
Cardiac disorders	1/18 (5.6%)	1
Cardiac disorders	1/18 (5.6%)	1
Endocrine disorders
Endocrine disorders	1/18 (5.6%)	2
Gastrointestinal disorders
Gastrointestinal disorders	2/18 (11.1%)	2
Gastrointestinal disorders	1/18 (5.6%)	1
Gastrointestinal disorders	3/18 (16.7%)	3
Gastrointestinal disorders	3/18 (16.7%)	3
Gastrointestinal disorders	1/18 (5.6%)	2
Gastrointestinal disorders	1/18 (5.6%)	1
Gastrointestinal disorders	1/18 (5.6%)	1
General disorders
General disorders and administration site conditions	1/18 (5.6%)	2
General disorders and administration site conditions	3/18 (16.7%)	7
General disorders and administration site conditions	1/18 (5.6%)	1
General disorders and administration site conditions	1/18 (5.6%)	2
General disorders and administration site conditions	1/18 (5.6%)	1
Immune system disorders
Immune system disorders	1/18 (5.6%)	1
Infections and infestations
Infections and infestations	2/18 (11.1%)	2
Infections and infestations	1/18 (5.6%)	1
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications	2/18 (11.1%)	2
Investigations
Investigations	2/18 (11.1%)	2
Investigations	1/18 (5.6%)	1
Investigations	2/18 (11.1%)	3
Investigations	1/18 (5.6%)	1
Metabolism and nutrition disorders
Metabolism and nutrition disorders	1/18 (5.6%)	1
Metabolism and nutrition disorders	1/18 (5.6%)	2
Metabolism and nutrition disorders	1/18 (5.6%)	1
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorders	3/18 (16.7%)	4
Nervous system disorders
Nervous system disorders	1/18 (5.6%)	1
Nervous system disorders	1/18 (5.6%)	3
Nervous system disorders	1/18 (5.6%)	2
Renal and urinary disorders
Renal and urinary disorders	1/18 (5.6%)	1
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders	1/18 (5.6%)	1
Respiratory, thoracic and mediastinal disorders	1/18 (5.6%)	1
Respiratory, thoracic and mediastinal disorders	1/18 (5.6%)	1
Respiratory, thoracic and mediastinal disorders	1/18 (5.6%)	1
Respiratory, thoracic and mediastinal disorders	1/18 (5.6%)	1
Respiratory, thoracic and mediastinal disorders	1/18 (5.6%)	1
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders	1/18 (5.6%)	1
Skin and subcutaneous tissue disorders	1/18 (5.6%)	2

Limitations/Caveats

One patient changed administration schedule for C2D15 in cycle 2 due to family vacation plan. The variance in dates was submitted to IRB and the patient was approved to continue on treatment when returns from the trip. One patient was unable to travel from Puerto Rico due to hurricane devastation. Dose C2D15 skipped in cycle 2. Medications were given one or two day(s) earlier or later than the scheduled date for a few patients.

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.