Phase 1-2 of a CpG-Activated Whole Cell Vaccine Followed by Autologous Immunotransplant for MCL

• Sponsor: Ronald Levy (Other)
• Overall Status: Completed
• CT.gov ID: NCT00490529
• Collaborator: National Institutes of Health (NIH) (NIH)
• Enrollment: 59
• Location: 1
• Arm: 1
• Duration (Months): 100.4
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

Mantle cell lymphoma (MCL) is a sub-type of non-Hodgkin's lymphoma (NHL) which is generally considered incurable with current therapy. Participants will receive an autologous vaccine against their individual lymphoma after undergoing stem cell transplantation. This vaccination may prolong the time which patients will stay in remission from their disease.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, Mantle-Cell	Biological: CpG-MCL vaccine; Biological: PF-3512676; Procedure: Vaccine-primed T-cells; Procedure: Autologous hematopoietic stem cell transplant (HSCT); Drug: Rituximab; Drug: Standard induction chemotherapy; Drug: Cyclophosphamide; Drug: Filgrastim	Phase 2

Detailed Description

Study treatment is a complex set of steps of research procedures and regular medical care. By using a participant's cancer cells as an immungen, the study hopes to improve freedom from molecular residual disease (MRD).

PRIMARY OBJECTIVE Freedom from molecular residual disease at 1-year post-autologous transplant.

SECONDARY OBJECTIVE Time To Clinical Progression (TTP)

This study has 2 research agents, PF-03152676 and CpG-MCL Vaccine.

PF-03152676 is a synthetic DNA molecule, 24 nucleotides in length with a nuclease-resistant phosphorothioate backbone. It is an immunostimulatory, single-stranded oligodeoxynucleotide (oligo-DNA) containing unmethylated cytosine and guanine (CpG) motifs and synthesized with a nuclease-resistant phosphorothioate backbone. PF-03512676 acts as an agonist of human Toll-like receptor 9, leading to activation of antigen-presenting cells and a cascade of anti-tumor immune reactions.

CpG-MCL Vaccine is the primary study agent. It is prepared by dissociating a participant's harvested tumor cells into a single-cell suspension, and culturing them with PF-03152676 for 72 hours at 37 degrees C, 5% CO2 to allow for up-regulation of antigen-presenting and co-stimulatory molecules, then irradiated to 200 Gy to destroy any remaining cancer propagating ability.

The study procedure is summarized as 12 steps, listed below.

• Step 1. Undergo excisional tumor biopsy or apheresis to obtain tumor cells, which will be used to generate the CpG-MCL vaccine .

• Step 2. Receive standard induction chemotherapy (regular medical care).

• Step 3. Once in remission, receive 3 vaccinations of CpG-MCL Vaccine over 3 weeks. With each CpG-MCL vaccination, a concurrent subcutaneous injection of PF-3512676 is administered as an adjuvant.

• Step 4. About 4 weeks later, receive rituximab 375 mg/m² to minimize any residual tumor.

• Step 5. Apheresis procedure to harvest the CpG-MCL Vaccine-primed T-cells. Each collection is ~1 x 10e10 CD3+ T-cells.

• Step 6. High-dose cytoxan and filgrastim to mobilize peripheral blood progenitor cell (PBPC).

• Step 7. Undergo separate apheresis procedure to harvest PBPC).

• Step 8. Receive myeloablative chemotherapy (regular medical care).

• Step 9. Receive PBPC infusion (also known as autologous hematopoietic cell transplant, AHCT).

• Step 10. Within 3 days of AHCT (but typically 1 day), receive infusion of CpG-MCL Vaccine-primed T-cells, followed within 1 hour by a with 4th vaccination with CpG-MCL Vaccine (1st booster vaccination).

• Step 11. After hematopoietic recovery, receive 5th vaccination with CpG-MCl (2nd booster vaccination).

• Step 12. Monitor participants for general health and disease status through at least 3 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 59 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 1-2 Study of a CpG-Activated Whole Cell Vaccine Followed by Autologous "Immunotransplant" for Mantle Cell Lymphoma
• Study Start Date: Aug 1, 2009
• Actual Primary Completion Date: Dec 14, 2017
• Actual Study Completion Date: Dec 14, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: CpG-MCL Vaccine An autologous anti-tumor vaccine.

Biological: CpG-MCL vaccine; CpG-MCL vaccine is a vaccine prepared by co-culturing cells from the participant's mantle cell lymphoma suspension with 3 mcg/mL PF-3512676, then irradiated to 200 Gy. 1 x 10e8 CpG-MCL cells will be given as a subcutaneous injection.; Other Names: CpG-activated, autologous tumor vaccine Cytosine-Guanosine repeats (CpG)-mantle cell lymphoma (CpG-MCL vaccine) ; Biological: PF-3512676; PF-03152676 is a synthetic immunostimulatory, single-stranded oligodeoxynucleotide (oligo-DNA) moledule containing unmethylated cytosine and guanine (CpG) motifs. PF-03512676 acts as an agonist of human Toll-like receptor 9, leading to activation of antigen-presenting cells and a cascade of antitumor immune reactions.; Other Names: CPG-7909 ; Procedure: Vaccine-primed T-cells; Vaccine primed T-cells are the post-vaccination leukapheresis harvest of peripheral blood mononuclear cells. Each collection is approx 1 x 10e10 CD3+ T-cells.; Procedure: Autologous hematopoietic stem cell transplant (HSCT); Regular medical procedure; Other Names: Autologous peripheral blood progenitor cell (PBPC) transplant Autologous peripheral blood stem cell (PBSC) transplant ; Drug: Rituximab; 375 mg/m² by infusion; Other Names: Rituxan hera ; Drug: Standard induction chemotherapy; Patient-specific, regular medical care treatment as determined by treating oncologist; Drug: Cyclophosphamide; Regular medical care treatment to mobilize peripheral blood progenitor cell (PBPC); Other Names: Cytoxtan Neosar CYT CTX CPM ; Drug: Filgrastim; Regular medical care treatment to mobilize peripheral blood progenitor cell (PBPC); Other Names: G-CSF Neupogen

Outcome Measures

Primary Outcome Measures

1. Freedom From Molecular Residual Disease (MRD) Post-autologous Stem Cell Transplant (ASCT) [12 months]

   Molecular residual disease (MRD) is defined as detection in blood samples by the ClonoSEQ test of the (11;14) (q13;q32) gene translocation. It is considered positive if a tumor-specific VDJ sequence is detected in the peripheral blood cells by Ig-HTS at a frequency of greater or equal to 1 molecule per 10,000 input leukocyte equivalents of DNA within 1 year post-autologous stem cell transplant (ASCT). The outcome will be reported as number and percent of participants that maintain MRD-negative status (ie, 1-year freedom from MRD). This outcome is reported as a number without dispersion.

Secondary Outcome Measures

1. Time-to-progression (TTP) [7.7 years]

   Time-to-progression (TTP) is measured from the time of autologous stem cell transplantation (ASCT) until the cancer progresses or relapses. Progression is assessed based on CT imaging per the Cheson Criteria (2008). Progression per the Cheson Criteria is defined as having occurred when the sum of tumor lesion dimensions is ≥ 150% of the baseline value. The outcome is reported as the median with 95% confidence interval, as determined by Kaplan-Meier analysis and log-rank test.

2. Overall Survival (OS) [After 1, 2, 3, 4, and 5 years]

   Overall survival (OS) rate is reported as number and percentage of participants remaining alive the date of transplant through each year, up to 5 years (reported as a number without dispersion).

3. Detection of Tumor-specific CD8-positve Memory T-cells Before and After Vaccination [Baseline and after vaccination and transplant, approximately 5 years]

   Anti-tumor T-cell immune responses were evaluated by an in vitro evocative test on their peripheral blood mononuclear cell (PBMCs) before and after vaccination, as assessed by measurement of intracellular cytokines and/or intracellular perforin/granzyme in CD8+ T-cells, and/or CD137 induction on CD4+ T-cells. PBMCs were co-cultured with CpG-activated autologous MCL tumor cells and evaluated for tumor-specific immune responses as measured by CD137 expression on their T cells. The outcome is reported as the number of participants for whom tumor-specific memory CD8 cells were detected at baseline and after vaccination and transplant (numbers without dispersion).

4. Detection of Tumor-specific CD4-positve T-cells Before and After Vaccination [Baseline and after vaccination and transplant, approximately 5 years]

   Anti-tumor T-cell immune responses were evaluated by an in vitro evocative test on their peripheral blood mononuclear cell (PBMCs) before and after vaccination, as assessed by measurement of intracellular cytokines and/or intracellular perforin/granzyme in CD8+ T-cells, and/or CD137 induction on CD4+ T-cells. PBMCs were co-cultured with CpG-activated autologous MCL tumor cells and evaluated for tumor-specific immune responses as measured by CD137 expression on their T cells. The outcome is reported as the number of participants for whom tumor-specific memory CD4 cells were detected at baseline and after transplant (numbers without dispersion).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

INCLUSION CRITERIA

• Newly-diagnosed with mantle cell lymphoma (MCL) with accessible disease site for excisional biopsy, OR have sufficient peripheral blood tumor to leukapherese ≥ 1.5 x 10e9 lymphoma cells in a single session

• Medically appropriate by standard clinical criteria to receive rituximab and standard induction chemotherapy and high-dose chemotherapy with autologous hematopoietic cell transplant (AHCT)

• HIV-negative

• Eastern Cooperative Oncology Group (ECOG) Performance Status, OR Karnofsky performance scale 50 to 100%

• Capable of providing informed consent

EXCLUSION CRITERIA

• Currently receiving immunosuppressive medications

• Severe psychological or medical illness

• Pregnant or lactating

• Unable to safely complete the study, at the discretion of the principal investigator

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University Medical Center	Stanford	California	United States	94305

Sponsors and Collaborators

• Ronald Levy
• National Institutes of Health (NIH)

Investigators

• Principal Investigator: Ronald Levy, MD, Stanford University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 4, 2016

More Information

Publications

• Brody JD, Goldstein MJ, Czerwinski DK, Levy R. Immunotransplantation preferentially expands T-effector cells over T-regulatory cells and cures large lymphoma tumors. Blood. 2009 Jan 1;113(1):85-94. doi: 10.1182/blood-2008-05-155457. Epub 2008 Sep 23.

• Responsible Party: Ronald Levy, Professor, Stanford University
• ClinicalTrials.gov Identifier: NCT00490529
• Other Study ID Numbers: IRB-05089; LYMNHL0040-BMT212; 96940; NCI-2011-00136
• First Posted: Jun 22, 2007
• Last Update Posted: Jan 13, 2020
• Last Verified: Jan 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Mantle-Cell; Cyclophosphamide; Rituximab; Vaccines

Study Results

Participant Flow

Recruitment Details	Some participants started study procedures, but did not receive the intended study treatment.

Arm/Group Title	CpG-MCL Vaccine
Arm/Group Description	An autologous anti-tumor vaccine.
Period Title: Completed Pre-CpG-MCL Vaccine Procedures
STARTED	59
COMPLETED	48
NOT COMPLETED	11
Period Title: Completed Pre-CpG-MCL Vaccine Procedures
STARTED	48
COMPLETED	47
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	CpG-MCL Vaccine
Arm/Group Description	An autologous anti-tumor vaccine.
Overall Participants	59
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	17 28.8%
>=65 years	42 71.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58 (8.3)
Sex: Female, Male (Count of Participants)
Female	20 33.9%
Male	39 66.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 5.1%
Not Hispanic or Latino	56 94.9%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	3 5.1%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 1.7%
White	54 91.5%
More than one race	0 0%
Unknown or Not Reported	1 1.7%
Region of Enrollment (participants) [Number]
United States	59 100%

Outcome Measures

1. Primary Outcome

Title	Freedom From Molecular Residual Disease (MRD) Post-autologous Stem Cell Transplant (ASCT)
Description	Molecular residual disease (MRD) is defined as detection in blood samples by the ClonoSEQ test of the (11;14) (q13;q32) gene translocation. It is considered positive if a tumor-specific VDJ sequence is detected in the peripheral blood cells by Ig-HTS at a frequency of greater or equal to 1 molecule per 10,000 input leukocyte equivalents of DNA within 1 year post-autologous stem cell transplant (ASCT). The outcome will be reported as number and percent of participants that maintain MRD-negative status (ie, 1-year freedom from MRD). This outcome is reported as a number without dispersion.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Only participants for which molecular residual disease (MRD) disease status assessments were available are included.

Arm/Group Title	CpG-MCL Vaccine
Arm/Group Description	An autologous anti-tumor vaccine. CpG-MCL vaccine: CpG-MCL vaccine is a vaccine prepared by co-culturing cells from the participant's mantle cell lymphoma suspension with 3 mcg/mL PF-3512676, then irradiated to 200 Gy. 1 x 10e8 CpG-MCL cells will be given as a subcutaneous injection. PF-3512676: PF-03152676 is a synthetic immunostimulatory, single-stranded oligodeoxynucleotide (oligo-DNA) moledule containing unmethylated cytosine and guanine (CpG) motifs. Vaccine-primed T-cells: Vaccine primed T-cells are the post-vaccination leukapheresis harvest of peripheral blood mononuclear cells. Each collection is approx 1 x 10e10 CD3+ T-cells. Autologous hematopoietic stem cell transplant (HSCT): Regular medical procedure Rituximab: 375 mg/m² by infusion Standard induction chemotherapy: Patient-specific, regular medical care treatment as determined by treating oncologist Cyclophosphamide: Regular medical care treatment to mobilize peripheral blood progenitor cell (PBPC)
Measure Participants	45
Count of Participants [Participants]	41 69.5%

2. Secondary Outcome

Title	Time-to-progression (TTP)
Description	Time-to-progression (TTP) is measured from the time of autologous stem cell transplantation (ASCT) until the cancer progresses or relapses. Progression is assessed based on CT imaging per the Cheson Criteria (2008). Progression per the Cheson Criteria is defined as having occurred when the sum of tumor lesion dimensions is ≥ 150% of the baseline value. The outcome is reported as the median with 95% confidence interval, as determined by Kaplan-Meier analysis and log-rank test.
Time Frame	7.7 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CpG-MCL Vaccine
Arm/Group Description	An autologous anti-tumor vaccine. CpG-MCL vaccine: CpG-MCL vaccine is a vaccine prepared by co-culturing cells from the participant's mantle cell lymphoma suspension with 3 mcg/mL PF-3512676, then irradiated to 200 Gy. 1 x 10e8 CpG-MCL cells will be given as a subcutaneous injection. PF-3512676: PF-03152676 is a synthetic immunostimulatory, single-stranded oligodeoxynucleotide (oligo-DNA) moledule containing unmethylated cytosine and guanine (CpG) motifs. Vaccine-primed T-cells: Vaccine primed T-cells are the post-vaccination leukapheresis harvest of peripheral blood mononuclear cells. Each collection is approx 1 x 10e10 CD3+ T-cells. Autologous hematopoietic stem cell transplant (HSCT): Regular medical procedure Rituximab: 375 mg/m² by infusion Standard induction chemotherapy: Patient-specific, regular medical care treatment as determined by treating oncologist Cyclophosphamide: Regular medical care treatment to mobilize peripheral blood progenitor cell (PBPC)
Measure Participants	47
Median (95% Confidence Interval) [years]	6.9

3. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall survival (OS) rate is reported as number and percentage of participants remaining alive the date of transplant through each year, up to 5 years (reported as a number without dispersion).
Time Frame	After 1, 2, 3, 4, and 5 years

Outcome Measure Data

Analysis Population Description

Only participants that received the CpG-MCL Vaccine are included.

Arm/Group Title	CpG-MCL Vaccine
Arm/Group Description	An autologous anti-tumor vaccine. CpG-MCL vaccine: CpG-MCL vaccine is a vaccine prepared by co-culturing cells from the participant's mantle cell lymphoma suspension with 3 mcg/mL PF-3512676, then irradiated to 200 Gy. 1 x 10e8 CpG-MCL cells will be given as a subcutaneous injection. PF-3512676: PF-03152676 is a synthetic immunostimulatory, single-stranded oligodeoxynucleotide (oligo-DNA) moledule containing unmethylated cytosine and guanine (CpG) motifs. Vaccine-primed T-cells: Vaccine primed T-cells are the post-vaccination leukapheresis harvest of peripheral blood mononuclear cells. Each collection is approx 1 x 10e10 CD3+ T-cells. Autologous hematopoietic stem cell transplant (HSCT): Regular medical procedure Rituximab: 375 mg/m² by infusion Standard induction chemotherapy: Patient-specific, regular medical care treatment as determined by treating oncologist Cyclophosphamide: Regular medical care treatment to mobilize peripheral blood progenitor cell (PBPC)
Measure Participants	48
OS after 1 year	42 71.2%
OS after 2 year	33 55.9%
OS after 3 year	27 45.8%
OS after 4 year	19 32.2%
OS after 5 year	13 22%

4. Secondary Outcome

Title	Detection of Tumor-specific CD8-positve Memory T-cells Before and After Vaccination
Description	Anti-tumor T-cell immune responses were evaluated by an in vitro evocative test on their peripheral blood mononuclear cell (PBMCs) before and after vaccination, as assessed by measurement of intracellular cytokines and/or intracellular perforin/granzyme in CD8+ T-cells, and/or CD137 induction on CD4+ T-cells. PBMCs were co-cultured with CpG-activated autologous MCL tumor cells and evaluated for tumor-specific immune responses as measured by CD137 expression on their T cells. The outcome is reported as the number of participants for whom tumor-specific memory CD8 cells were detected at baseline and after vaccination and transplant (numbers without dispersion).
Time Frame	Baseline and after vaccination and transplant, approximately 5 years

Outcome Measure Data

Analysis Population Description

Only participants for which both baseline and post-transplant assessments were available are included.

Arm/Group Title	CpG-MCL Vaccine
Arm/Group Description	An autologous anti-tumor vaccine. CpG-MCL vaccine: CpG-MCL vaccine is a vaccine prepared by co-culturing cells from the participant's mantle cell lymphoma suspension with 3 mcg/mL PF-3512676, then irradiated to 200 Gy. 1 x 10e8 CpG-MCL cells will be given as a subcutaneous injection. PF-3512676: PF-03152676 is a synthetic immunostimulatory, single-stranded oligodeoxynucleotide (oligo-DNA) moledule containing unmethylated cytosine and guanine (CpG) motifs. Vaccine-primed T-cells: Vaccine primed T-cells are the post-vaccination leukapheresis harvest of peripheral blood mononuclear cells. Each collection is approx 1 x 10e10 CD3+ T-cells. Autologous hematopoietic stem cell transplant (HSCT): Regular medical procedure Rituximab: 375 mg/m² by infusion Standard induction chemotherapy: Patient-specific, regular medical care treatment as determined by treating oncologist Cyclophosphamide: Regular medical care treatment to mobilize peripheral blood progenitor cell (PBPC)
Measure Participants	35
At Baseline	31 52.5%
After Transplant	14 23.7%

5. Secondary Outcome

Title	Detection of Tumor-specific CD4-positve T-cells Before and After Vaccination
Description	Anti-tumor T-cell immune responses were evaluated by an in vitro evocative test on their peripheral blood mononuclear cell (PBMCs) before and after vaccination, as assessed by measurement of intracellular cytokines and/or intracellular perforin/granzyme in CD8+ T-cells, and/or CD137 induction on CD4+ T-cells. PBMCs were co-cultured with CpG-activated autologous MCL tumor cells and evaluated for tumor-specific immune responses as measured by CD137 expression on their T cells. The outcome is reported as the number of participants for whom tumor-specific memory CD4 cells were detected at baseline and after transplant (numbers without dispersion).
Time Frame	Baseline and after vaccination and transplant, approximately 5 years

Outcome Measure Data

Analysis Population Description

Only participants for which both baseline and post-transplant assessments were available are included.

Arm/Group Title	CpG-MCL Vaccine
Arm/Group Description	An autologous anti-tumor vaccine. CpG-MCL vaccine: CpG-MCL vaccine is a vaccine prepared by co-culturing cells from the participant's mantle cell lymphoma suspension with 3 mcg/mL PF-3512676, then irradiated to 200 Gy. 1 x 10e8 CpG-MCL cells will be given as a subcutaneous injection. PF-3512676: PF-03152676 is a synthetic immunostimulatory, single-stranded oligodeoxynucleotide (oligo-DNA) moledule containing unmethylated cytosine and guanine (CpG) motifs. Vaccine-primed T-cells: Vaccine primed T-cells are the post-vaccination leukapheresis harvest of peripheral blood mononuclear cells. Each collection is approx 1 x 10e10 CD3+ T-cells. Autologous hematopoietic stem cell transplant (HSCT): Regular medical procedure Rituximab: 375 mg/m² by infusion Standard induction chemotherapy: Patient-specific, regular medical care treatment as determined by treating oncologist Cyclophosphamide: Regular medical care treatment to mobilize peripheral blood progenitor cell (PBPC)
Measure Participants	35
At Baseline	20 33.9%
After Transplant	14 23.7%

Adverse Events

Time Frame	3 months
Adverse Event Reporting Description	The study has 2 stages, ie, procedures preceding vaccine administration + the vaccine treatment period. All cause mortality includes the entire subject population (ie, both pre-vaccine period and actual treatment period). Serious Adverse Events and Other (Not Including Serious) Adverse Events information includes only the participants that received the vaccine and transplant (actual study treatment period).
Arm/Group Title	CpG-MCL Vaccine
Arm/Group Description	An autologous anti-tumor vaccine.
All Cause Mortality
	CpG-MCL Vaccine
	Affected / at Risk (%)	# Events
Total	19/59 (32.2%)
Serious Adverse Events
	CpG-MCL Vaccine
	Affected / at Risk (%)	# Events
Total	31/48 (64.6%)
Blood and lymphatic system disorders
Blood and lymphatic system disorders - Other, Graft failure	1/48 (2.1%)	1
Febrile Neutropenia	1/48 (2.1%)	1
Neutrophils/granulocytes (ANC/AGC)	1/48 (2.1%)	2
Platelets	1/48 (2.1%)	1
General disorders
Death NOS	2/48 (4.2%)	2
Infections and infestations
Infection, dental abscess	1/48 (2.1%)	1
Investigations
Leukocytes (total WBC)	2/48 (4.2%)	2
Musculoskeletal and connective tissue disorders
Myositis	1/48 (2.1%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Death Disease progression	12/48 (25%)	12
Nervous system disorders
Hemorrhage, CNS, Intracranial hemorrhage	1/48 (2.1%)	1
Respiratory, thoracic and mediastinal disorders
Adult Respiratory Distress Syndrome (ARDS)	1/48 (2.1%)	1
Pneumonitis	4/48 (8.3%)	4
Skin and subcutaneous tissue disorders
Burn	1/48 (2.1%)	1
Vascular disorders
Thrombosis/embolism	1/48 (2.1%)	1
Supraventricular and nodal arrhythmia	1/48 (2.1%)	1
Other (Not Including Serious) Adverse Events
	CpG-MCL Vaccine
	Affected / at Risk (%)	# Events
Total	48/48 (100%)
Blood and lymphatic system disorders
Febrile neutropenia	2/48 (4.2%)	2
Leukocytes count low	3/48 (6.3%)	3
Lymphocytes count low	1/48 (2.1%)	1
Platelets count low	2/48 (4.2%)	2
Gastrointestinal disorders
Abdomen NOS	1/48 (2.1%)	1
Anorexia	4/48 (8.3%)	7
Diarrhea	4/48 (8.3%)	5
Distension/bloating Abdominal (Gas/indigestion)	1/48 (2.1%)	2
Heartburn/dyspepsia	5/48 (10.4%)	6
Mucositis/Stomatitis	1/48 (2.1%)	1
Nausea	3/48 (6.3%)	4
Vomiting	2/48 (4.2%)	2
General disorders
Fatigue	25/48 (52.1%)	53
Fever	29/48 (60.4%)	63
Flu-like syndrome: General	4/48 (8.3%)	4
Injection site reaction/extravasation changes: Erythema	47/48 (97.9%)	123
Injection site reaction/extravasation changes: Pain	19/48 (39.6%)	39
Injection site reaction/extravasation changes: Swelling	24/48 (50%)	63
Injection site reaction/extravasation changes: Warmth	17/48 (35.4%)	35
Rigors/Chills	22/48 (45.8%)	45
Weight Loss	1/48 (2.1%)	1
Infections and infestations
Metapneumovirus	1/48 (2.1%)	1
Investigations
Neutrophils/granulocytes count low	4/48 (8.3%)	4
Musculoskeletal and connective tissue disorders
Pain Joint (Arthalgia)	16/48 (33.3%)	35
Hip pain	1/48 (2.1%)	1
Joint Function	1/48 (2.1%)	1
Myalgia	29/48 (60.4%)	62
Nervous system disorders
Dizziness	3/48 (6.3%)	3
Head/Headache	16/48 (33.3%)	26
Imsomnia	2/48 (4.2%)	3
Syncope	1/48 (2.1%)	1
Psychiatric disorders
Phantom sensations (sensitivity/crawly feeling on skin)	2/48 (4.2%)	2
Respiratory, thoracic and mediastinal disorders
Cough	4/48 (8.3%)	4
nasal congestion	1/48 (2.1%)	1
Pneumonitis	2/48 (4.2%)	2
Voice changes/dysarthia	1/48 (2.1%)	1
Skin and subcutaneous tissue disorders
Hyperpigmentation	2/48 (4.2%)	2
Induration	14/48 (29.2%)	21
Other: Granuloma	1/48 (2.1%)	1
Other: thinning/fragile skin	2/48 (4.2%)	2
Pruritis/Itching	12/48 (25%)	15
Rash/Desquamation	6/48 (12.5%)	6
Vascular disorders
Thrombosis	1/48 (2.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.