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| ID | Type | Description | Link |
|---|---|---|---|
| NA_00073453 | Other Identifier | JHMIRB |
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| Name | Class |
|---|---|
| David H. Koch Charitable Foundation | UNKNOWN |
| BioSante Pharmaceuticals | INDUSTRY |
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This research is being done to see if an investigational prostate cancer vaccine, called GVAX, can safely be given together with a single intravenous injection of a drug called cyclophosphamide to men that will undergo surgery to remove their cancerous prostate glands who have also received standard hormonal therapy.
Cancer immunotherapy refers broadly to approaches which attempt to treat cancer by activating immune responses directed against malignant tissue. Prostate GVAX is an allogeneic cell-based prostate cancer vaccine composed of two irradiated cell lines (PC3 and LNCaP) that have been genetically modified to secrete granulocyte-macrophage colony-stimulating factor (granulocytemacrophage-colony stimulating factor). The release of granulocytemacrophage-colony stimulating factor by these modified tumor cells serves to recruit dendritic cells which then present tumor antigens to T-cells, thus initiating antitumor immune responses.
However, abundant preclinical data show that, when used alone, cell-based immunotherapy is unable to break specific T-cell tolerance in tumor-bearing hosts. Studies in an autochthonous prostate cancer mouse model have shown that giving low-dose cyclophosphamide prior to a cell-based granulocytemacrophage-colony stimulating factor-secreting vaccine abrogates immune tolerance through augmentation of CD8+ T cell infiltration in the prostate, transient depletion of regulatory T cells (Tregs), and increased expression of dendritic cell maturation markers. Enhancement of antitumor immunity has also been observed in other preclinical models where cyclophosphamide was given in sequence with granulocytemacrophage-colony stimulating factor-secreting immunotherapy for the treatment of breast and pancreatic cancers. These preclinical data are supported by early-phase clinical trials combining GVAX with low-dose cyclophosphamide in pancreatic and breast cancers.
Furthermore, emerging evidence suggests that androgen deprivation therapy (ADT) itself has profound effects on the host immune system, resulting in thymic regeneration and enhancement of antitumor immunity. In addition, preclinical and clinical studies demonstrate that ADT augments prostate cancer-specific immune responses induced by immunotherapy, suggesting that ADT may act synergistically with immunotherapy. Based on data from mouse models as well as human clinical trials, it has been suggested that prostate cancer immunotherapy may be most effective when administered in the setting of an androgen-suppressed environment.
Building on these findings, investigators have designed a study to assess the use of ADT given alone or administered following immunization with low-dose cyclophosphamide and prostate GVAX, in patients undergoing radical prostatectomy. Investigators aim (1) to determine whether ADT is immunogenic in men with localized prostate cancer by evaluating T-cell infiltration in harvested prostate glands; (2) to determine whether administering ADT after low-dose cyclophosphamide and prostate GVAX augments immune infiltration into the prostate gland; and (3) to investigate whether this combinatorial immuno-hormonal approach is safe and feasible. Investigators hypothesize that the combination of ADT and cyclophosphamide/GVAX will produce significantly greater antitumor immune responses than would ADT used alone.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Degarelix | Active Comparator | Degarelix will be administered as three 80 mg subcutaneous injections, for a total dose of 240 mg at 14 (±3) days prior to surgery. A telephone follow-up interview (or an in-person clinic visit) to evaluate for adverse events will occur 28 (±21) days after prostatectomy. Patients will then be followed by their urologists according to standard institutional practices, but will require prostate-specific antigen evaluations every 3 (±1) months during year 1 and every 6 (±2) months during years 2-3. |
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| Cyclophosphamide, GVAX and Degarelix | Experimental | Cyclophosphamide will be given at a dose of 200 mg/m2 as a single intravenous infusion. 1 day later, prostate GVAX will be administered as five 0.8-mL intradermal injections of PC3 (2.5 × 108 cells) and five 0.5-mL intradermal injections of LNCaP (2.5 × 108 cells), for a total dose of 5 × 108 cells. On day 14, Degarelix will be administered as three 80 mg subcutaneous injections, for a total dose of 240 mg. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| degarelix acetate | Drug | Degarelix Acetate is a gonadotropin-releasing hormone (GnRH) receptor antagonist. It works by decreasing the amount of testosterone in the body,which the tumor needs to grow. |
| Measure | Description | Time Frame |
|---|---|---|
| Intraprostatic CD8+ T Cell Infiltration | CD8+ T cell infiltration (quantified as log[CD8 density]) into the prostate from harvested prostate glands in men with localized prostate cancer receiving neoadjuvant Androgen deprivation therapy alone (2 weeks prior to surgery), or cyclophosphamide and GVAX followed by Androgen deprivation therapy, (with cyclophosphamide/GVAX administered 4 weeks prior to prostatectomy, and Androgen deprivation therapy administered 2 weeks prior to prostatectomy). | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Intraprostatic CD4+ T Cell and Treg Infiltration | Number of participants with CD4+ T cell and Treg infiltration into the prostate. | 2 years |
| Quantification of Tissue Androgen Concentrations | Tissue androgen concentrations (testosterone, dihydrotestosterone), and androgen receptor (AR) protein expression in prostate specimens |
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Inclusion Criteria:
Histologically confirmed adenocarcinoma of the prostate (clinical stage T1c-T3b, N0, M0) without involvement of lymph nodes, bone, or visceral organs
Initial prostate biopsy is available for central pathologic review, and is confirmed to show at least 2 positive cores and a maximum Gleason sum of ≥ 7
Radical prostatectomy has been scheduled at Johns Hopkins Hospital
Age ≥ 21 years
Eastern Cooperative Oncology Group performance status 0-1, or Karnofsky score ≥ 70%
Adequate bone marrow, hepatic, and renal function:
Willingness to provide written informed consent and HIPAA authorization for the release of personal health information, and the ability to comply with the study requirements (note: HIPAA authorization will be included in the informed consent)
Willingness to use barrier contraception from the time of cyclophosphamide and/or GVAX administration until the time of prostatectomy.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Emmanual Antonarakis, M.D | Johns Hopkins University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore | Maryland | 21231 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Degarelix | Degarelix will be administered as three 80 mg subcutaneous injections, for a total dose of 240 mg at 14 (±3) days prior to surgery. A telephone follow-up interview (or an in-person clinic visit) to evaluate for adverse events will occur 28 (±21) days after prostatectomy. Patients will then be followed by their urologists according to standard institutional practices, but will require prostate-specific antigen evaluations every 3 (±1) months during year 1 and every 6 (±2) months during years 2-3. degarelix acetate: Degarelix Acetate is a gonadotropin-releasing hormone (GnRH) receptor antagonist. It works by decreasing the amount of testosterone in the body,which the tumor needs to grow. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 30, 2012 |
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| Cyclophosphamide | Drug | Cyclophosphamide as a potent enhancer of immune responses to GVAX. cyclophosphamide is used as an immune suppressor in many autoimmune disorders. |
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| GVAX | Drug | GVAX is granulocytemacrophage -colony stimulating factor -secreting allogeneic cell-based vaccine as immunotherapy for prostate cancer |
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| 2 years |
| Quantification of Markers of Apoptosis | Amount of apoptosis (activated caspase 3) and proliferation (Ki-67) in prostate tumor specimens | 2 years |
| Pathological Complete Responses | Number of participants with pathological complete response (pCR) | 2 years |
| Serum Antibodies to Prostate-associated Antigens | Number of participants with generation of novel antibodies to prostate-associated antigens in the serum of patients, after the initiation of protocol therapy | 2 years |
| Prostate-specific Antigen Response Rate | Number of participants with Prostate-specific antigen response | 2 years |
| Percentage of Participants Without Prostate Specific Antigen Recurrence at 24 Months After Surgery | Percentage of participants in each arm who were free of prostate specific antigen recurrence (i.e. prostate specific antigen remained undetectable after prostatectomy) at 24 months after undergoing surgery. | 2 years |
| FG001 | Cyclophosphamide, GVAX and Degarelix | Cyclophosphamide will be given at a dose of 200 mg/m2 as a single intravenous infusion. 1 day later, prostate GVAX will be administered as five 0.8-mL intradermal injections of PC3 (2.5 × 108 cells) and five 0.5-mL intradermal injections of LNCaP (2.5 × 108 cells), for a total dose of 5 × 108 cells. On day 14, Degarelix will be administered as three 80 mg subcutaneous injections, for a total dose of 240 mg. degarelix acetate: Degarelix Acetate is a gonadotropin-releasing hormone (GnRH) receptor antagonist. It works by decreasing the amount of testosterone in the body,which the tumor needs to grow. Cyclophosphamide: Cyclophosphamide as a potent enhancer of immune responses to GVAX. cyclophosphamide is used as an immune suppressor in many autoimmune disorders. GVAX: GVAX is granulocytemacrophage-colony stimulating factor -secreting allogeneic cell-based vaccine as immunotherapy for prostate cancer |
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| NOT COMPLETED |
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Only participants who were randomized and underwent prostatectomy.
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| ID | Title | Description |
|---|---|---|
| BG000 | Degarelix | Degarelix will be administered as three 80 mg subcutaneous injections, for a total dose of 240 mg at 14 (±3) days prior to surgery. A telephone follow-up interview (or an in-person clinic visit) to evaluate for adverse events will occur 28 (±21) days after prostatectomy. Patients will then be followed by their urologists according to standard institutional practices, but will require prostate-specific antigen evaluations every 3 (±1) months during year 1 and every 6 (±2) months during years 2-3. degarelix acetate: Degarelix Acetate is a gonadotropin-releasing hormone (GnRH) receptor antagonist. It works by decreasing the amount of testosterone in the body,which the tumor needs to grow. |
| BG001 | Cyclophosphamide, GVAX and Degarelix | Cyclophosphamide will be given at a dose of 200 mg/m2 as a single intravenous infusion. 1 day later, prostate GVAX will be administered as five 0.8-mL intradermal injections of PC3 (2.5 × 108 cells) and five 0.5-mL intradermal injections of LNCaP (2.5 × 108 cells), for a total dose of 5 × 108 cells. On day 14, Degarelix will be administered as three 80 mg subcutaneous injections, for a total dose of 240 mg. degarelix acetate: Degarelix Acetate is a gonadotropin-releasing hormone (GnRH) receptor antagonist. It works by decreasing the amount of testosterone in the body,which the tumor needs to grow. Cyclophosphamide: Cyclophosphamide as a potent enhancer of immune responses to GVAX. cyclophosphamide is used as an immune suppressor in many autoimmune disorders. GVAX: GVAX is granulocytemacrophage-colony stimulating factor -secreting allogeneic cell-based vaccine as immunotherapy for prostate cancer |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Intraprostatic CD8+ T Cell Infiltration | CD8+ T cell infiltration (quantified as log[CD8 density]) into the prostate from harvested prostate glands in men with localized prostate cancer receiving neoadjuvant Androgen deprivation therapy alone (2 weeks prior to surgery), or cyclophosphamide and GVAX followed by Androgen deprivation therapy, (with cyclophosphamide/GVAX administered 4 weeks prior to prostatectomy, and Androgen deprivation therapy administered 2 weeks prior to prostatectomy). | Posted | Mean | 95% Confidence Interval | log10 (cells/mm^2) | 2 years |
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| Secondary | Intraprostatic CD4+ T Cell and Treg Infiltration | Number of participants with CD4+ T cell and Treg infiltration into the prostate. | Data was not collected for this outcome measure | Posted | 2 years |
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| Secondary | Quantification of Tissue Androgen Concentrations | Tissue androgen concentrations (testosterone, dihydrotestosterone), and androgen receptor (AR) protein expression in prostate specimens | Data was not collected for this outcome measure | Posted | 2 years |
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| Secondary | Quantification of Markers of Apoptosis | Amount of apoptosis (activated caspase 3) and proliferation (Ki-67) in prostate tumor specimens | Data was not collected for this outcome measure | Posted | 2 years |
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| Secondary | Pathological Complete Responses | Number of participants with pathological complete response (pCR) | Posted | Count of Participants | Participants | 2 years |
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| Secondary | Serum Antibodies to Prostate-associated Antigens | Number of participants with generation of novel antibodies to prostate-associated antigens in the serum of patients, after the initiation of protocol therapy | Data was not collected for this outcome measure | Posted | 2 years |
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| Secondary | Prostate-specific Antigen Response Rate | Number of participants with Prostate-specific antigen response | Posted | Count of Participants | Participants | 2 years |
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| Secondary | Percentage of Participants Without Prostate Specific Antigen Recurrence at 24 Months After Surgery | Percentage of participants in each arm who were free of prostate specific antigen recurrence (i.e. prostate specific antigen remained undetectable after prostatectomy) at 24 months after undergoing surgery. | Posted | Number | 95% Confidence Interval | percentage of participants | 2 years |
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Participants were assessed for adverse events after receiving study drug and before prostatectomy as well as doing each follow up visit after prostatectomy up to 3 years.
An adverse event (AE) is defined as any untoward medical occurrence (symptom, sign, illness or experience) that develops or worsens in a research patient during a clinical study or within 30 days post-treatment, regardless of causality.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Degarelix | Degarelix will be administered as three 80 mg subcutaneous injections, for a total dose of 240 mg at 14 (±3) days prior to surgery. A telephone follow-up interview (or an in-person clinic visit) to evaluate for adverse events will occur 28 (±21) days after prostatectomy. Patients will then be followed by their urologists according to standard institutional practices, but will require prostate-specific antigen evaluations every 3 (±1) months during year 1 and every 6 (±2) months during years 2-3. degarelix acetate: Degarelix Acetate is a gonadotropin-releasing hormone (GnRH) receptor antagonist. It works by decreasing the amount of testosterone in the body,which the tumor needs to grow. | 0 | 15 | 1 | 15 | 15 | 15 |
| EG001 | Cyclophosphamide, GVAX and Degarelix | Cyclophosphamide will be given at a dose of 200 mg/m2 as a single intravenous infusion. 1 day later, prostate GVAX will be administered as five 0.8-mL intradermal injections of PC3 (2.5 × 108 cells) and five 0.5-mL intradermal injections of LNCaP (2.5 × 108 cells), for a total dose of 5 × 108 cells. On day 14, Degarelix will be administered as three 80 mg subcutaneous injections, for a total dose of 240 mg. degarelix acetate: Degarelix Acetate is a gonadotropin-releasing hormone (GnRH) receptor antagonist. It works by decreasing the amount of testosterone in the body,which the tumor needs to grow. Cyclophosphamide: Cyclophosphamide as a potent enhancer of immune responses to GVAX. cyclophosphamide is used as an immune suppressor in many autoimmune disorders. GVAX: GVAX is GM-CSF-secreting allogeneic cell-based vaccine as immunotherapy for prostate cancer | 0 | 14 | 2 | 14 | 14 | 14 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hematoma | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
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| Stroke | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
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| Thromboembolic event | Vascular disorders | CTCAE (4.0) | Systematic Assessment | Pulmonary embolism |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fatigue | General disorders | CTCAE (4.0) | Systematic Assessment |
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| Injection site reaction | General disorders | CTCAE (4.0) | Systematic Assessment | erythema bilateral legs |
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| Urinary Incontinence | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
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| Hypertriglyceridemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
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| Alkaline Phosphatase | Investigations | CTCAE (4.0) | Systematic Assessment | Increased Alkaline Phosphatase |
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| Bullous dermatitis | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment | Shingles (right side of body) |
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| Creatinine increased | Investigations | CTCAE (4.0) | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | CTCAE (4.0) | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | CTCAE (4.0) | Systematic Assessment |
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| Premature menopause | Reproductive system and breast disorders | CTCAE (4.0) | Systematic Assessment | hot flashes |
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| Cystitis noninfective | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment | nocturia |
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| Erectile dysfunction | Reproductive system and breast disorders | CTCAE (4.0) | Systematic Assessment |
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| Allergic reaction | Immune system disorders | CTCAE (4.0) | Systematic Assessment | allergic reaction/erythema |
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| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Anemia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
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| Blood bilirubin increased | Investigations | CTCAE (4.0) | Systematic Assessment |
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| Facial nerve disorder | Nervous system disorders | CTCAE (4.0) | Systematic Assessment | facial nerve disorder (Bell's Palsy) |
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| Allergic rhinitis | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment | nasal congestion |
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| Fever | General disorders | CTCAE (4.0) | Systematic Assessment |
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| Lethargy | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
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| atrial fibrillation | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
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| Atrial flutter | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Insomnia | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
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| Generalized muscle weakness | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment | muscle soreness (legs) |
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| Urinary tract infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment | lower abdominal pain |
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| Arthralgia | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
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| Restlessness | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment | restless/ anxious |
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| Peripheral sensory neuropathy | Nervous system disorders | CTCAE (4.0) | Systematic Assessment | peri-oral numbness |
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| Weight gain | Investigations | CTCAE (4.0) | Systematic Assessment |
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| Thromboembolic event | Vascular disorders | CTCAE (4.0) | Systematic Assessment | pulmonary embolism |
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| Chills | General disorders | CTCAE (4.0) | Systematic Assessment |
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| Perineal pain | Reproductive system and breast disorders | CTCAE (4.0) | Systematic Assessment |
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| Anxiety | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
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| Oral dysesthesia | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment | swollen tongue |
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| Eye disorders - Other, | Eye disorders | CTCAE (4.0) | Systematic Assessment | soreness around eyes |
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| Constipation | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Paresthesia | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
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| Headache | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Emmanuel S. Antonarakis, M.D., principal investigator | Johns Hopkins University | 443-287-0553 | eantona1@jhmi.edu |
| Sep 28, 2018 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| C431566 | acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide |
| D003520 | Cyclophosphamide |
| ID | Term |
|---|---|
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
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| >=65 years |
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| Male |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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