Trial document




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  DRKS00012869

Trial Description

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Title

Phase 1/2 Trial to determine the Response Rate of Nivolumab in Acute Myeloid Leukemia (AML) relapse after Allogeneic Hematopoietic Cell Transplantation (allo-HCT)

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Trial Acronym

NIFAR

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URL of the Trial

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Brief Summary in Lay Language

The planned clinical study will focus on improving the treatment of AML recurrence with the drug Nivolumab. Nivolumab binds to the surface of certain immune cells, the so-called T-lymphocytes, and increases your activity. This strong activation of the immune system leads to long-term tumor regression in some diseases. There is already an approval for the treatment of lung, skin, kidney, bladder, Hodgkin's lymphoma and others.

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Brief Summary in Scientific Language

Our preliminary data demonstrate that immune checkpoint blockade with nivolumab leads to potent activation of the graft-versus-leukemia (GvL) effect in patients with AML relapse after allo-HCT. We therefore intend to launch a clinical phase1/2 trial. The primary objective of this phase 1/2 trial is a first evaluation of the efficacy and safety of nivolumab treatment in patients with AML relapse after allo-HCT in 2 transplantation centers in Germany. We will determine the response by monitoring peripheral blood smears and bone marrow specimens.
CTP AM02 18.02.19, Change of Inclusion- and Exclusion criteria, EK Votum 14.03.19

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Organizational Data

  •   DRKS00012869
  •   2018/03/19
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  •   yes
  •   Approved
  •   5/18 (FF-MC), Ethik-Kommission der Albert-Ludwigs-Universität Freiburg
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Secondary IDs

  •   2017-002194-18 
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Health Condition or Problem studied

  •   C92.0 -  Acute myeloblastic leukaemia [AML]
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Interventions/Observational Groups

  •   Treatment with nivolumab 3 mg/kg body weight (BW) IV infused over 1 hour; repeat treatment every 2 weeks for 12 weeks
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Characteristics

  •   Interventional
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  •   Single arm study
  •   Open (masking not used)
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  •   Uncontrolled/Single arm
  •   Treatment
  •   Single (group)
  •   I-II
  •   No
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Primary Outcome

The primary endpoint is the Overall response rate (ORR) to treatment after 6 and 12 weeks of induction therapy

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Secondary Outcome

•Time to treatment response
•Proportion of patients with treatment failure
•Response duration
•Overall survival (OS)
•Progression-free survival (PFS)
•Non Relapse Mortality (NRM)
•Changes in alloreactive T cell phenotype and metabolism during treatment
•Quality of life (EORTC QLQ-C30 and QLQ-HDC29)

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
  • University Medical Center 
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Recruitment

  •   Actual
  •   2018/05/07
  •   20
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Months
  •   no maximum age
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Additional 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 re-screened.
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.

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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 <90% by pulse-oximetry, require vasopressors, and/or have NYHA class III or IV heart failure
6.Abnormal liver function tests (serum total bilirubin >1,5 x ULN; or in case of liver infiltration by AML, serum (total) bilirubin > 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 calculatedcreatinine 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

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Addresses

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    • Ärztlicher Direktor,Universitätsklinikum Freiburg
    • Breissacher Str. 153
    • 79110  Freiburg
    • Germany
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    • Medical Center - University of Freiburg Albert-Ludwigs-University Freiburg Department of Medicine ISpecialties: Hematology, Oncology, and Stem-Cell Transplantation
    • Mr.  Prof. Dr.  Robert  Zeiser 
    • Hugstetter Str. 55
    • 79106  Freiburg
    • Germany
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    • Medical Center - University of Freiburg Albert-Ludwigs-University FreiburgDepartment of Medicine ISpecialties: Hematology, Oncology, and Stem-Cell Transplantation
    • Mr.  Prof. Dr.  Robert  Zeiser 
    • Hugstetter Str. 55
    • 79106  Freiburg
    • Germany
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Sources of Monetary or Material Support

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    • Universitätsklinikum FreiburgKlinik für Innere Medizin I, Hämatologie, Onkologie und Stammzelltransplantation
    • Hugstetter Str. 55
    • 79106  Freiburg
    • Germany
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    • Bristol-Myers Squibb GmbH & Co. KGaA
    • Arnulfstr. 29
    • 80636  München
    • Germany
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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