Acute myeloid leukemia relapse after allo-HCT MedDRA version: 20.0 Level: LLT Classification code 10001941 Term: AML System Organ Class: 100000004864 MedDRA version: 20.0 Level: LLT Classification code 10066572 Term: AML progression System Organ Class: 100000004864
Conditions
Interventions
Trade Name: OPDIVO
Product Name: OPDIVO
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: NIVOLUMAB
Other
Sponsors
Medical Center - University of Freiburg
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Relapse of AML after allo-HCT from any donor source (matched unrelated donor, mismatched unrelated donor, sibling, haploidentical) using bone marrow or peripheral blood stem cells at 3 months or more after allogeneic HCT. Patients can be rescreened. 2. Cytological or histological evidence of AML relapse including but not limited to bone marrow biopsy, extramedullary site biopsy or cerebrospinal fluid evaluation. 3. No immune suppression for at least 2 weeks prior to screening 4. 10% or more donor-derived chimerism measured within 4 weeks prior to day 0 5. Male and female patients aged =18 years 6. ECOG performance status 0, 1, or 2 7. No other superior treatment approach (second allo-HCT) available 8. At least 1 cycle of therapy with the hypomethylating agents decitabine or azacitidine between diagnosis of relapse and screening 9. Written informed consent 10. Ability to understand the nature, significance and consequences of the study and the study-related procedures and to comply with them. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. History or active acute GvHD grade III/IV 2. Chronic GvHD requiring systemic immunosuppressive treatment at the time of screening 3. Active autoimmune diseases 4. Active treatment in a clinical study of any investigational agent within 30 days prior day 0 or within 5 half-lives of the study treatment, whichever is greater 5. Mechanical ventilation or patients who have resting O2 saturation 5 x ULN, serum alanine or aspartate aminotransferase >3 × ULN or in case of liver infiltration by AML, AST and/or ALT > 5 x ULN) 7. Abnormal kidney function tests (calculated creatinine clearance =30 ml/min by the Cockcroft-Gault equation) 8. Severe hematological impairment (platelets <10 000/µl, hemoglobin level <8 mg/dl unless attributable to AML infiltration of the BM), there is no lower limit for neutrophil counts because AML relapse leads to low neutrophil numbers and treatment with nivolumab could improve this by eradicating the leukemia 9. Active uncontrolled bacterial, viral or fungal infection 10. Positivity for HIV, Hepatitis B or Hepatitis C at the time of screening 11. Active or latent tuberculosis infection that has developed after allo-HCT 12. Previous or concurrent malignancies within the last 3 years of enrolment except for adequately treated basal cell or squamous cell skin cancer, or any other cancer from which the subject has been disease-free for more than 3 years 13. Uncontrolled hypertension or ventricular arrhythmias 14. Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the subject; or interfere with interpretation of study data 15. Known allergies, hypersensitivity, or intolerance of the study medication, excipients, or similar compounds 16. Female patients who are pregnant or breast feeding 17. Female patients of child-bearing potential who are not willing to use highly effective methods of contraception during the trial and at least 5 months after the last dose of nivolumab (see also 10.9)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: To assess time to treatment response To assess rate of patients with treatment failure To assess duration of response To assess Overall Survival (OS) To assess Progression-free surviv-al (PFS) To assess Non Relapse Mortality (NRM) To assess changes in alloreactive T cell phenotype and metabolism during treatment To assess quality of life To assess incidence and severity of GvHD To assess incidence of infectious complications To assess the incidence and severity of immune-related adverse events ;Primary end point(s): Overall response rate (ORR) at weeks 6 and 12 after treatment start.;Timepoint(s) of evaluation of this end point: Weeks 6 and 12 after treatment start;Main Objective: Overall response rate (ORR) to treatment after 6 and 12 weeks of induction therapy | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Time to response is defined as time from treatment start to the date of first documentation PR, CR, CRi or morphologic leukemia-free state. Death without prior response will be considered to be a competing event. Rate of patients with treatment failure until month 3 after treatment start. The duration of response is assessed for responders only by calculating the time from first response to the date of first observation of AML relapse/progression or the date of additional systemic treatment for AML. Death without prior observation of disease progres-sion is considered as a competing event. OS is defined as time from treatment start to the date of death from any cause. PFS is defined as the time from treatment start to the date of recurrence or progression of AML or death from any cause, whichever occurs first NRM is defined as the time from treatment start to the date of death not preceded by hematologic dis-ease recurrence. Hematologic disease recurrence / progression is considered to be a competing event Changes in alloreactive T cell phenotype and metabolism EORTC QLQ-C30 and EORTC QLQ-C29 Cumulative incidence rates of patients who develop acute or chronic GvHD as defined by the diagnostic criteria of the Harris et al for acute GvHD20 and according to the NIH criteria for chronic GvHD21. Death without prior GvHD is considered as a competing event Rate of patients who develop bacterial, viral or fun-gal infections which require pharmacological treat-ment (cumulative incidence rate) Frequency and severity of immune-mediated adverse events ;Timepoint(s) of evaluation of this end point: 18 months after randomization of last patient | — |
Countries
Germany
Contacts
Public ContactEarly Clinical Trial Unit
Universitätklinikum Freiburg, Klinik für Innere Medizin 1
Outcome results
None listed