Preliminary Assessment of Safety and Tolerability of Dostarlimab in Combination Antiretroviral Therapy (cART) Refractory HIV Associated Kaposi Sarcoma
- Conditions
- Refractory HIV Associated Kaposi Sarcoma
- Registration Number
- NCT05646082
- Lead Sponsor
- Imperial College London
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 20
Inclusion Criteria:<br><br> 1. Histologically proven diagnosis of Kaposi Sarcoma.<br><br> 2. Available pretreatment biopsy, either fresh (optimal) or archival (acceptable).<br><br> 3. Established on cART for at least 3 months and no symptomatic or laboratory AE<br> associated with cART > grade 1 by CTCAE criteria v 5.0.<br><br> Note: modifications of cART during screening are allowed provided patients meet all<br> other eligibility criteria and are on effective new regimen for at least 2 weeks.<br><br> 4. Have an HIV VL<200 cp/ml and CD4+ T-cell count >100/mm3 at screening.<br><br> 5. Have disease that is measurable by modified AIDS Clinical Trial Group (ATCG) Kaposi<br> sarcoma response criteria.<br><br> 6. Eastern Cooperative Oncology Group (ECOG) performance status of = 2<br><br> 7. Be of = 18 years of age<br><br> 8. Have adequate haematological and organ function, defined as follows:<br><br> Absolute neutrophil count >1.500/mcL, Platelet count >100.000/mcL, Haemoglobin >90<br> g/L, Total bilirubin =1.5x upper limit of normal (ULN) or =2xULN for patients with<br> Gilbert's syndrome or on HIV protease inhibitors, Aspartate aminotransferase<br> (AST)/alanine aminotransferase (ALT) =2.5x ULN (up to 5x ULN if liver metastases are<br> present), Serum creatinine =2.5x ULN or creatinine clearance (CrCl) >60 ml/min in<br> subjects with serum creatinine =1.5x ULN. Calculation of CrCl should follow<br> institutional standards.<br><br> International normalized ratio (INR) or prothrombin time (PT) =1.5× ULN unless<br> patient is receiving anticoagulant therapy as long as PT or partial thromboplastin<br> (PTT) is within therapeutic range of intended use of anticoagulants. Activated<br> partial thromboplastin time (aPTT) =1.5× ULN unless patient is receiving<br> anticoagulant therapy as long as PT or PTT is within therapeutic range of intended<br> use of anticoagulants.<br><br> 9. Female participants must have a negative serum pregnancy test within 72 hours prior<br> to taking study treatment if of childbearing potential and agree use a highly<br> effective method of contraception from screening through 120 days after the last<br> dose of study treatment or is of nonchildbearing potential. Nonchildbearing<br> potential is defined as follows (by other than medical reasons):<br><br> - =45 years of age and has not had menses for >1 year<br><br> - Patients who have been amenorrhoeic for <2 years without history of a<br> hysterectomy and oophorectomy must have a follicle stimulating hormone value in<br> the postmenopausal range upon screening evaluation<br><br> - Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation.<br> Documented hysterectomy or oophorectomy must be confirmed with medical records<br> of the actual procedure or confirmed by an ultrasound. Tubal ligation must be<br> confirmed with medical records of the actual procedure, otherwise the patient<br> must be willing to use an adequate birth control method throughout the study,<br> starting with the screening visit through 120 days after the last dose of study<br> treatment. See Section 5.4 for a list of acceptable birth control methods.<br> Information must be captured appropriately within the site's source documents.<br> Note: Abstinence is acceptable if this is the established and preferred<br> contraception for the patient.<br><br> 10. Participant must agree to not breastfeed during the study or for 90 days after the<br> last dose of study treatment.<br><br> 11. Male participant agrees to use a highly effective method of contraception (see<br> Section 5.4 for a list of acceptable birth control methods) starting with the first<br> dose of study treatment through 120 days after the last dose of study treatment.<br> Note: Abstinence is acceptable if this is the established and preferred<br> contraception for the patient.<br><br> 12. Participant receiving corticosteroids may continue as long as their dose is stable<br> for least 4 weeks prior to initiating protocol therapy Participant must be able to<br> understand the study procedures and agree to participate in the study by providing<br> written informed consent.<br><br>Exclusion Criteria:<br><br> 1. Participant is simultaneously enrolled in any interventional clinical trial.<br><br> 2. Participant has received anti-cancer therapy (chemotherapy, radiation therapy,<br> immunotherapy or biologic therapy) including investigational therapy = 4 weeks, or<br> within a time interval less than at least 5 half-lives of the investigational agent,<br> whichever is shorter, prior initiating protocol therapy. There should be no evidence<br> of treatment-related adverse events > grade 1 by CTCAE criteria.<br><br> 3. Major surgery within 3 weeks prior to initiating protocol therapy. Study participant<br> must have recovered from any adverse events relating to surgery.<br><br> 4. Known active tuberculosis (TB) in the first 6 weeks of treatment.<br><br> 5. Known active Immune Reconstitution Inflammatory Syndrome (IRIS) related to<br> opportunistic pathogens.<br><br> Note: Patients with previous history of IRIS that has fully resolved at the time of<br> screening are eligible.<br><br> 6. Known history of active uncontrolled hepatitis C virus (HCV) infection, defined as<br> detectable plasma HCV RNA.<br><br> Note: patients with positive HCV serology but negative HCV RNA or those successfully<br> treated for HCV are eligible.<br><br> 7. Known history of active uncontrolled hepatitis B virus (HBV) infection, defined as<br> detectable plasma HBV DNA in absence of therapy.<br><br> Note: patients with HBV serology indicating immunization (i.e. positive hepatitis B<br> surface antibody, HBsAb and negative core antibody HBcAb), patients with fully<br> resolved acute HBV infection and those with chronic HBV infection adequately treated<br> with antiviral therapy are eligible.<br><br> 8. Active autoimmune disease that has required systemic treatment in the past 2 years<br> (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive<br> drugs). Replacement therapy (eg. thyroxine, insulin, or physiologic corticosteroid<br> replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered<br> a form of systemic treatment.<br><br> 9. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced<br> pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on<br> screening chest computed tomography scan.<br><br> 10. Prior therapy with anti-PD-1/PD-L1 and/or anti-CTLA-4 therapy either alone or in<br> combination with other agents.<br><br> 11. Receipt of live vaccines within 30 days before the first dose of trial treatment and<br> while participating in the trial; examples of live vaccines include, but are not<br> limited to, the following: measles, mumps, rubella, chicken pox, yellow fever,<br> seasonal flu, H1N1 flu, rabies, bacillus Calmette-Guerin (BCG), and typhoid vaccine.<br><br> 12. Known hypersensitivity to dostarlimab components or excipients.<br><br> 13. Evidence of serious, uncontrolled medical disorder, non-malignant systemic disease,<br> or active, uncontrolled infection.<br><br> 14. History or current evidence of any condition, therapy, or laboratory abnormality<br> that might confound the results of the trial, interfere with the patient's<br> participation for the full duration of the trial, or is not in the best interest of<br> the patient to participate, in the opinion of the treat
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Incidence of treatment-emergent adverse events (safety and tolerability)
- Secondary Outcome Measures
Name Time Method Improvement of progression-free survival rate (efficacy)