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Immunotherapy in Combination With Prednisone and Sirolimus for Kidney Transplant Recipients With Unresectable or Metastatic Skin Cancer

Primary Purpose

Clinical Stage III Cutaneous Melanoma AJCC v8, Clinical Stage III Merkel Cell Carcinoma AJCC v8, Clinical Stage IV Cutaneous Melanoma AJCC v8

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Biopsy
Biospecimen Collection
Computed Tomography
Ipilimumab
Kidney Biopsy
Magnetic Resonance Imaging
Nivolumab
Prednisone
Sirolimus
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Clinical Stage III Cutaneous Melanoma AJCC v8

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients must be kidney transplant recipients with a functioning allograft who do not currently require dialysis Patient's age must be >= 18 years. Because no dosing or adverse event (AE) data are currently available on the use of nivolumab and ipilimumab in kidney transplant recipients <18 years of age, children are excluded from this study, but may be eligible for future pediatric trials Patients must have histologically or cytologically confirmed non-uveal melanoma, basal cell carcinoma, Merkel cell carcinoma, or cutaneous squamous cell carcinoma for which standard non-immunological medical, surgical, or radiation therapy would be insufficient (i.e., patients who are not surgical candidates). Patients with cutaneous squamous cell carcinoma or Merkel cell carcinoma may enroll without prior medical therapy (e.g., cetuximab or chemotherapy respectively). Non-immunologic standard therapies that patients must have received, refused or for which patients were ineligible include: For patients with BRAF-mutant melanoma, prior therapies include BRAF/MEK inhibitors For patients with Basal cell carcinoma, prior therapies include hedgehog pathway inhibitors Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, i.e., at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm by chest x-ray or as >= 10 mm with CT scan, magnetic resonance imaging (MRI), or calipers by clinical exam is preferred, but not required Patients must have Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%) performance status criteria Leukocytes >= 2,000/mcL Absolute neutrophil count >= 1,500/mcL Platelets >= 50,000/mcL Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 x institutional ULN Serum creatinine =< 3 x ULN dd-cfDNA =< 1.0% and =< 61% increase The effects of nivolumab and ipilimumab on the developing human fetus are unknown. For this reason, and because other therapeutic agents used in this trial are known to be teratogenic, women of childbearing potential (WOCBP) receiving nivolumab must continue contraception for a period of 5 months after the last dose of nivolumab. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) as well as azoospermic men do not require contraception. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of beta-human chorionic gonadotropin [B-HCG]) during the screening period. Follow-up evaluations will include interval sexual/menstrual histories as needed. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she (or the participating partner) should inform the treating physician immediately. WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. Women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL to be considered postmenopausal. Human immunodeficiency virus (HIV)-infected patients will be eligible for this trial if they are on effective antiretroviral regimens utilizing non-CYP-interactive agents and have an undetectable viral load. If there is evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable on suppressive therapy, if indicated. If there is history of hepatitis C virus (HCV) infection, the patient must have been treated and have undetectable HCV viral load. Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants Exclusion Criteria: Patients who have received a liver, lung, heart, or pancreas transplant; or allogeneic stem cell transplant; or any kind of bone marrow transplant Patients unwilling or unable to undergo dialysis in the event of allograft failure Patients with prior evidence of human leukocyte antigen (HLA) or non-HLA donor-specific antibodies (DSA) Patients with a history of antibody- or cell-mediated allograft rejection within 3 months of study entry Potential trial participants should have recovered from clinically significant adverse events of their most recent therapy/intervention prior to enrollment Patients must not have had prior treatment for their current cancer with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-LAG-3 or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways within 1 year of study enrollment. Prior history of adjuvant therapy is allowed if received over 1 year prior to enrollment Patients must not be receiving any other investigational agents Patients with leptomeningeal metastases, more than 3 untreated central nervous system (CNS) metastases, untreated brain metastases measuring >1cm, or requiring treatment-dose steroids (> 10 mg/day prednisone equivalents) for CNS-related symptoms. Exclusions are due to concerns regarding progressive neurologic dysfunction that would confound the evaluation of neurologic and other AEs. Patients with brain metastases meeting the above requirements are permitted to enroll Patients must not have a history of severe hypersensitivity reaction to any monoclonal antibody Patients must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to other agents used in the study Patients must not have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or any other significant condition(s) that would make this protocol unreasonably hazardous Pregnant women are excluded from this study because nivolumab and ipilimumab have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued if the mother is treated with nivolumab or ipilimumab. These potential risks may also apply to other agents used in this study Patients with autoimmune disease that is active or might recur and affect vital organ function will be eligible only after consultation with the study PI. Guillain-Barre (GB) syndrome, bullous skin disease, Stevens Johnson syndrome, or toxic epidermal necrolysis will be excluded Patients must not have had evidence of active or acute diverticulitis, intra-abdominal abscess, GI obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation should be evaluated for the potential need for additional treatment before coming on study. In addition, patients with a history of cardiac disease including coronary artery disease (CAD), myocardial infarction (MI), cardiomyopathy, arrhythmia, heart block, should have an evaluation by history pulmonary embolism (PE) and appropriate testing to allow evaluation of any events that may occur on study. These may include troponin, electrocardiogram (EKG), echocardiogram (ECHO) as clinically indicated and may include results already in the medical record if available

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Treatment (nivolumab and ipilimumab)

    Arm Description

    See detailed description

    Outcomes

    Primary Outcome Measures

    Disease control without allograft loss
    Defined as complete or partial response (CR; PR) or stable disease (SD), at 14 weeks per response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. The percent of kidney transplant recipients who experience CR/PR/SD at 14 weeks and do not experience allograft loss after administration of nivolumab, ipilimumab, sirolimus, and prednisone will be calculated, along with the corresponding exact 95% confidence interval (CI).

    Secondary Outcome Measures

    Objective response rate (ORR)
    Defined as the proportion of subjects whose best overall response from baseline is either a CR or PR, based on RECIST 1.1 criteria. ORR will be estimated along with 95% exact CI.
    Rate of allograft loss and rejection
    Renal allograft rejection rate will be estimated as the proportion of subjects who experience markers of allograft rejection. Allograft loss is defined as allograft rejection leading to complete, permanent, and irreversible loss-of-function of the renal allograft.
    Duration of response (DOR) among patients who experience CR or PR
    DOR will be summarized using the Kaplan-Meier method.
    Progression-free survival (PFS)
    Kaplan-Meier curves will be used to summarize PFS.
    Overall survival
    Kaplan-Meier curves will be used to summarize OS.

    Full Information

    First Posted
    June 8, 2023
    Last Updated
    September 12, 2023
    Sponsor
    National Cancer Institute (NCI)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05896839
    Brief Title
    Immunotherapy in Combination With Prednisone and Sirolimus for Kidney Transplant Recipients With Unresectable or Metastatic Skin Cancer
    Official Title
    A Phase 1/2 Study of Nivolumab and Ipilimumab in Combination With Sirolimus and Prednisone in Kidney Transplant Recipients With Selected Unresectable or Metastatic Cutaneous Cancers
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    December 8, 2023 (Anticipated)
    Primary Completion Date
    January 31, 2027 (Anticipated)
    Study Completion Date
    January 31, 2027 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    National Cancer Institute (NCI)

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    This phase I/II trial tests the combination of nivolumab and ipilimumab with sirolimus and prednisone for the treatment of skin (cutaneous) cancer that cannot be removed by surgery (unresectable) or that has spread from where it first started to other places in the body (metastatic) in kidney transplant recipients. Immunotherapy with nivolumab and ipilimumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Sirolimus and prednisone are immunosuppressants that are given to keep the body from rejecting the transplanted kidney. Giving nivolumab and ipilimumab in combination with sirolimus and prednisone may kill more cancer cells, while also keeping the transplanted kidney healthy, in patients with unresectable or metastatic cutaneous cancer who have received a kidney transplant.
    Detailed Description
    PRIMARY OBJECTIVE: I. To evaluate the proportion of kidney transplant recipients with selected advanced cutaneous cancers who at 14 weeks after administration of prednisone, sirolimus, nivolumab, and ipilimumab experience complete response (CR), partial response (PR), or stable disease (SD) without allograft loss. SECONDARY OBJECTIVE: I. To estimate the objective response rate (ORR), rate of allograft loss, and durations of progression-free survival (PFS) and overall survival (OS) in the study population. EXPLORATORY OBJECTIVES: I. To characterize correlates of the host immune response including, but not limited to: Ia. Histopathological characteristics of allograft rejection/loss; Ib. Immunological changes in the tumor microenvironment (e.g., changes in T-cell subset populations or expression of immune checkpoint molecules) in paired biopsies obtained pre-treatment and on-treatment; Ic. Characteristics of anti-programmed death-1 (PD-1)-associated immune-mediated adverse reactions (IMARs) in this patient population treated with immunosuppression; Id. To evaluate molecular determinants of response using next generation sequencing and other sequencing techniques. II. To observe whether changes in donor-derived cell-free deoxyribonucleic acid (DNA) (dd-cfDNA) as a marker for allograft rejection. III. To compare baseline patient allograft/donor characteristics, to include human leukocyte antigen (HLA) status, date of transplant, presence of donor specific antibodies, history of prior rejection, and Calculated Panel Reactive Antibodies score, in patients who experience and do not experience rejection while on this study. IV. To observe the objective response rate (ORR) of patients who achieve PR/CR or stable disease for >= 6 months with eventual progressive disease requiring re-induction with nivolumab + ipilimumab (receive > 4 doses of nivolumab + ipilimumab). OUTLINE: Patients receive sirolimus orally (PO) and prednisone PO daily, starting 7 days prior to cycle 1 day 1 of immunotherapy. Patients also receive nivolumab intravenously (IV) over 30 minutes and ipilimumab IV over 30 minutes on day 8 of cycle 1 and day 1 of cycle 2.. 6 weeks after the first dose of nivolumab and ipilimumab, patients undergo tumor response assessment. Patients who achieve stable disease (SD), partial response (PR), or complete response (CR) receive nivolumab IV on day 1 of each cycle. Cycles repeat every 4 weeks for a total of 24 cycles in the absence of disease progression or unacceptable toxicity. Patients who had disease progression at this time or any time on trial may receive nivolumab IV and ipilimumab IV on day 1 of each cycle. Cycles repeat every 3 weeks for 2 cycles, in the absence of unacceptable toxicity. Patients are then assessed for tumor response again after 6 weeks and receive nivolumab monotherapy if they achieve SD, PR, or CR. If patients have progressive disease, they may receive nivolumab monotherapy or discontinue study treatment. Patients undergo computed tomography (CT) scan at screening, at cycle 3 day 1, on day 1 of odd numbered cycles, and at follow up. Patients may undergo magnetic resonance imaging (MRI) at screening. Patients undergo tumor biopsy at cycle 1 day 8, cycle 2 day 1. Patients may undergo kidney biopsy if rejection is suspected. Patients undergo blood sample collection on cycle 1 day 8, cycle 2 day 1, at disease progression and if an immune mediated adverse reaction occurs. Patients follow up every 12 weeks for 1 year after stopping therapy, then every 16 weeks for the second year after stopping and then every 20 weeks for up to 5 years.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Clinical Stage III Cutaneous Melanoma AJCC v8, Clinical Stage III Merkel Cell Carcinoma AJCC v8, Clinical Stage IV Cutaneous Melanoma AJCC v8, Clinical Stage IV Merkel Cell Carcinoma AJCC v8, Metastatic Basal Cell Carcinoma, Metastatic Carcinoma in the Skin, Metastatic Melanoma, Metastatic Merkel Cell Carcinoma, Metastatic Skin Squamous Cell Carcinoma, Unresectable Basal Cell Carcinoma, Unresectable Melanoma, Unresectable Merkel Cell Carcinoma, Unresectable Skin Squamous Cell Carcinoma

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1, Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    16 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Treatment (nivolumab and ipilimumab)
    Arm Type
    Experimental
    Arm Description
    See detailed description
    Intervention Type
    Procedure
    Intervention Name(s)
    Biopsy
    Other Intervention Name(s)
    BIOPSY_TYPE, Bx
    Intervention Description
    Undergo tumor biopsy
    Intervention Type
    Procedure
    Intervention Name(s)
    Biospecimen Collection
    Other Intervention Name(s)
    Biological Sample Collection, Biospecimen Collected, Specimen Collection
    Intervention Description
    Undergo blood sample collection
    Intervention Type
    Procedure
    Intervention Name(s)
    Computed Tomography
    Other Intervention Name(s)
    CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography
    Intervention Description
    Undergo CT scan
    Intervention Type
    Biological
    Intervention Name(s)
    Ipilimumab
    Other Intervention Name(s)
    Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, Ipilimumab Biosimilar CS1002, MDX-010, MDX-CTLA4, Yervoy
    Intervention Description
    Given IV
    Intervention Type
    Procedure
    Intervention Name(s)
    Kidney Biopsy
    Other Intervention Name(s)
    Biopsy of Kidney, Renal Biopsy
    Intervention Description
    Undergo kidney biopsy
    Intervention Type
    Procedure
    Intervention Name(s)
    Magnetic Resonance Imaging
    Other Intervention Name(s)
    Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging
    Intervention Description
    Undergo MRI
    Intervention Type
    Biological
    Intervention Name(s)
    Nivolumab
    Other Intervention Name(s)
    ABP 206, BMS-936558, CMAB819, MDX-1106, NIVO, Nivolumab Biosimilar ABP 206, Nivolumab Biosimilar CMAB819, ONO-4538, Opdivo
    Intervention Description
    Given IV
    Intervention Type
    Drug
    Intervention Name(s)
    Prednisone
    Other Intervention Name(s)
    .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl, Dacortin, DeCortin, Decortisyl, Decorton, Delta 1-Cortisone, Delta-Dome, Deltacortene, Deltacortisone, Deltadehydrocortisone, Deltasone, Deltison, Deltra, Econosone, Lisacort, Meprosona-F, Metacortandracin, Meticorten, Ofisolona, Orasone, Panafcort, Panasol-S, Paracort, Perrigo Prednisone, PRED, Predicor, Predicorten, Prednicen-M, Prednicort, Prednidib, Prednilonga, Predniment, Prednisone Intensol, Prednisonum, Prednitone, Promifen, Rayos, Servisone, SK-Prednisone
    Intervention Description
    Given PO
    Intervention Type
    Drug
    Intervention Name(s)
    Sirolimus
    Other Intervention Name(s)
    AY 22989, RAPA, Rapamune, Rapamycin, SILA 9268A, WY-090217
    Intervention Description
    Given PO
    Primary Outcome Measure Information:
    Title
    Disease control without allograft loss
    Description
    Defined as complete or partial response (CR; PR) or stable disease (SD), at 14 weeks per response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. The percent of kidney transplant recipients who experience CR/PR/SD at 14 weeks and do not experience allograft loss after administration of nivolumab, ipilimumab, sirolimus, and prednisone will be calculated, along with the corresponding exact 95% confidence interval (CI).
    Time Frame
    At 14 weeks
    Secondary Outcome Measure Information:
    Title
    Objective response rate (ORR)
    Description
    Defined as the proportion of subjects whose best overall response from baseline is either a CR or PR, based on RECIST 1.1 criteria. ORR will be estimated along with 95% exact CI.
    Time Frame
    Up to 5 years
    Title
    Rate of allograft loss and rejection
    Description
    Renal allograft rejection rate will be estimated as the proportion of subjects who experience markers of allograft rejection. Allograft loss is defined as allograft rejection leading to complete, permanent, and irreversible loss-of-function of the renal allograft.
    Time Frame
    Up to 5 years
    Title
    Duration of response (DOR) among patients who experience CR or PR
    Description
    DOR will be summarized using the Kaplan-Meier method.
    Time Frame
    From the time criteria are met for CR/PR (whichever is first recorded) until the first date that recurrent disease or PD is documented, up to 5 years
    Title
    Progression-free survival (PFS)
    Description
    Kaplan-Meier curves will be used to summarize PFS.
    Time Frame
    From the first dose of nivolumab + ipilimumab to the date of the first documented tumor progression or death due to any cause, whichever occurs first, up to 5 years
    Title
    Overall survival
    Description
    Kaplan-Meier curves will be used to summarize OS.
    Time Frame
    From the first dose of nivolumab + ipilimumab to the date of death from any cause, up to 5 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Patients must be kidney transplant recipients with a functioning allograft who do not currently require dialysis Patient's age must be >= 18 years. Because no dosing or adverse event (AE) data are currently available on the use of nivolumab and ipilimumab in kidney transplant recipients <18 years of age, children are excluded from this study, but may be eligible for future pediatric trials Patients must have histologically or cytologically confirmed non-uveal melanoma, basal cell carcinoma, Merkel cell carcinoma, or cutaneous squamous cell carcinoma for which standard non-immunological medical, surgical, or radiation therapy would be insufficient (i.e., patients who are not surgical candidates). Patients with cutaneous squamous cell carcinoma or Merkel cell carcinoma may enroll without prior medical therapy (e.g., cetuximab or chemotherapy respectively). Non-immunologic standard therapies that patients must have received, refused or for which patients were ineligible include: For patients with BRAF-mutant melanoma, prior therapies include BRAF/MEK inhibitors For patients with Basal cell carcinoma, prior therapies include hedgehog pathway inhibitors Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, i.e., at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm by chest x-ray or as >= 10 mm with CT scan, magnetic resonance imaging (MRI), or calipers by clinical exam is preferred, but not required Patients must have Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%) performance status criteria Leukocytes >= 2,000/mcL Absolute neutrophil count >= 1,500/mcL Platelets >= 50,000/mcL Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 x institutional ULN Serum creatinine =< 3 x ULN dd-cfDNA =< 1.0% and =< 61% increase The effects of nivolumab and ipilimumab on the developing human fetus are unknown. For this reason, and because other therapeutic agents used in this trial are known to be teratogenic, women of childbearing potential (WOCBP) receiving nivolumab must continue contraception for a period of 5 months after the last dose of nivolumab. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) as well as azoospermic men do not require contraception. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of beta-human chorionic gonadotropin [B-HCG]) during the screening period. Follow-up evaluations will include interval sexual/menstrual histories as needed. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she (or the participating partner) should inform the treating physician immediately. WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. Women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL to be considered postmenopausal. Human immunodeficiency virus (HIV)-infected patients will be eligible for this trial if they are on effective antiretroviral regimens utilizing non-CYP-interactive agents and have an undetectable viral load. If there is evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable on suppressive therapy, if indicated. If there is history of hepatitis C virus (HCV) infection, the patient must have been treated and have undetectable HCV viral load. Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants Exclusion Criteria: Patients who have received a liver, lung, heart, or pancreas transplant; or allogeneic stem cell transplant; or any kind of bone marrow transplant Patients unwilling or unable to undergo dialysis in the event of allograft failure Patients with prior evidence of human leukocyte antigen (HLA) or non-HLA donor-specific antibodies (DSA) Patients with a history of antibody- or cell-mediated allograft rejection within 3 months of study entry Potential trial participants should have recovered from clinically significant adverse events of their most recent therapy/intervention prior to enrollment Patients must not have had prior treatment for their current cancer with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-LAG-3 or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways within 1 year of study enrollment. Prior history of adjuvant therapy is allowed if received over 1 year prior to enrollment Patients must not be receiving any other investigational agents Patients with leptomeningeal metastases, more than 3 untreated central nervous system (CNS) metastases, untreated brain metastases measuring >1cm, or requiring treatment-dose steroids (> 10 mg/day prednisone equivalents) for CNS-related symptoms. Exclusions are due to concerns regarding progressive neurologic dysfunction that would confound the evaluation of neurologic and other AEs. Patients with brain metastases meeting the above requirements are permitted to enroll Patients must not have a history of severe hypersensitivity reaction to any monoclonal antibody Patients must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to other agents used in the study Patients must not have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or any other significant condition(s) that would make this protocol unreasonably hazardous Pregnant women are excluded from this study because nivolumab and ipilimumab have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued if the mother is treated with nivolumab or ipilimumab. These potential risks may also apply to other agents used in this study Patients with autoimmune disease that is active or might recur and affect vital organ function will be eligible only after consultation with the study PI. Guillain-Barre (GB) syndrome, bullous skin disease, Stevens Johnson syndrome, or toxic epidermal necrolysis will be excluded Patients must not have had evidence of active or acute diverticulitis, intra-abdominal abscess, GI obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation should be evaluated for the potential need for additional treatment before coming on study. In addition, patients with a history of cardiac disease including coronary artery disease (CAD), myocardial infarction (MI), cardiomyopathy, arrhythmia, heart block, should have an evaluation by history pulmonary embolism (PE) and appropriate testing to allow evaluation of any events that may occur on study. These may include troponin, electrocardiogram (EKG), echocardiogram (ECHO) as clinically indicated and may include results already in the medical record if available
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Evan J Lipson
    Organizational Affiliation
    JHU Sidney Kimmel Comprehensive Cancer Center LAO
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
    IPD Sharing URL
    https://grants.nih.gov/policy/sharing.htm

    Learn more about this trial

    Immunotherapy in Combination With Prednisone and Sirolimus for Kidney Transplant Recipients With Unresectable or Metastatic Skin Cancer

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