Back to resultsAnalysis of T Cell Metabolism in Relapsed AML Patients With DLIs and Bicanorm Treatment
Primary Purpose
Acute Myeloid Leukemia, in Relapse
Status
Completed
Phase
Early Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Bicanorm
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia, in Relapse
Eligibility Criteria
Inclusion Criteria:
- confirmed AML relapse after allo-HCT
- patients receiving DLIs
- age ≥ 18 years
- written informed consent
- ability to understand the nature of the study and the study related procedures and to comply with them
Exclusion Criteria:
- age < 18 years
- lack of informed consent
Sites / Locations
- Medical Center University of Freiburg
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
AML relapse under DLI and Bicanorm treatment
Arm Description
Analysis of T cell metabolism, immune phenotype and serum pH before and after Bicanorm (Sodium bicarbonate) treatment.
Outcomes
Primary Outcome Measures
T cell glycolytic activity
Extracellular acidification rate (ECAR) determined by live-cell metabolic assay using the Seahorse Analyzer
T cell respiratory activity
Oxygen consumption rate (OCR) determined by live-cell metabolic assay using the Seahorse Analyzer
T cell phenotype
T cell cytokine and effector molecule production determined by flow cytometric analysis
Secondary Outcome Measures
Serum pH
Measurement of serum pH
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04321161
Brief Title
Analysis of T Cell Metabolism in Relapsed AML Patients With DLIs and Bicanorm Treatment
Official Title
Analysis of T Cell Metabolism and Immune Phenotype in Relapsed Acute Myeloid Leukemia Patients Receiving Donor Lymphocyte Infusions and Bicanorm (Sodium Bicarbonate)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
February 25, 2020 (Actual)
Primary Completion Date
March 18, 2020 (Actual)
Study Completion Date
March 18, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Freiburg
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
In this study, the outcomes of relapsed AML patients receiving DLIs and Bicanorm (Sodium bicarbonate) were analyzed including T cell metabolism and immune phenotype.
Detailed Description
Acute myeloid leukemia (AML) patients suffering from relapse after allogeneic hematopoietic cell transplantation (allo-HCT) have a poor survival outcome. Donor lymphocyte infusions (DLIs) to induce graft-versus-leukemia (GvL) effects have a limited survival benefit.
Extensive preclinical studies have shown a beneficial effect of sodium bicarbonate on metabolic fitness of leukemia-reactive T cells in GvL AML models. Therefore, the investigators aimed to investigate a potential benefit of Bicanorm (Sodium bicarbonate) treatment accompanying DLIs in relapsed AML patients. The investigators determined the metabolic and immune phenotype of T cells isolated from patients receiving DLIs before and after Bicanorm (Sodium bicarbonate) treatment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, in Relapse
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AML relapse under DLI and Bicanorm treatment
Arm Type
Experimental
Arm Description
Analysis of T cell metabolism, immune phenotype and serum pH before and after Bicanorm (Sodium bicarbonate) treatment.
Intervention Type
Drug
Intervention Name(s)
Bicanorm
Other Intervention Name(s)
Sodium bicarbonate
Intervention Description
Treatment of patients with relapsed AML after allo-HCT receiving DLIs with Bicanorm (1-1-1) for 7 days.
sodium hydrogen carbonate (1 g per 1 tablet) = sodium ion (11,9 mmol per 1 tablet) = sodium ion (273 mg per 1 tablet) = hydrogen carbonate ion (11,9 mmol per 1 tablet)
Primary Outcome Measure Information:
Title
T cell glycolytic activity
Description
Extracellular acidification rate (ECAR) determined by live-cell metabolic assay using the Seahorse Analyzer
Time Frame
2 months
Title
T cell respiratory activity
Description
Oxygen consumption rate (OCR) determined by live-cell metabolic assay using the Seahorse Analyzer
Time Frame
2 months
Title
T cell phenotype
Description
T cell cytokine and effector molecule production determined by flow cytometric analysis
Time Frame
2 months
Secondary Outcome Measure Information:
Title
Serum pH
Description
Measurement of serum pH
Time Frame
2 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
confirmed AML relapse after allo-HCT
patients receiving DLIs
age ≥ 18 years
written informed consent
ability to understand the nature of the study and the study related procedures and to comply with them
Exclusion Criteria:
age < 18 years
lack of informed consent
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Zeiser, Prof. Dr.
Organizational Affiliation
Medical Center University of Freiburg
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medical Center University of Freiburg
City
Freiburg
State/Province
Baden-Württemberg
ZIP/Postal Code
79106
Country
Germany
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
26321679
Citation
Chang CH, Qiu J, O'Sullivan D, Buck MD, Noguchi T, Curtis JD, Chen Q, Gindin M, Gubin MM, van der Windt GJ, Tonc E, Schreiber RD, Pearce EJ, Pearce EL. Metabolic Competition in the Tumor Microenvironment Is a Driver of Cancer Progression. Cell. 2015 Sep 10;162(6):1229-41. doi: 10.1016/j.cell.2015.08.016. Epub 2015 Aug 27.
Results Reference
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PubMed Identifier
26719539
Citation
Pilon-Thomas S, Kodumudi KN, El-Kenawi AE, Russell S, Weber AM, Luddy K, Damaghi M, Wojtkowiak JW, Mule JJ, Ibrahim-Hashim A, Gillies RJ. Neutralization of Tumor Acidity Improves Antitumor Responses to Immunotherapy. Cancer Res. 2016 Mar 15;76(6):1381-90. doi: 10.1158/0008-5472.CAN-15-1743. Epub 2015 Dec 30. Erratum In: Cancer Res. 2017 May 1;77(9):2552.
Results Reference
background
PubMed Identifier
17909197
Citation
Schmid C, Labopin M, Nagler A, Bornhauser M, Finke J, Fassas A, Volin L, Gurman G, Maertens J, Bordigoni P, Holler E, Ehninger G, Polge E, Gorin NC, Kolb HJ, Rocha V; EBMT Acute Leukemia Working Party. Donor lymphocyte infusion in the treatment of first hematological relapse after allogeneic stem-cell transplantation in adults with acute myeloid leukemia: a retrospective risk factors analysis and comparison with other strategies by the EBMT Acute Leukemia Working Party. J Clin Oncol. 2007 Nov 1;25(31):4938-45. doi: 10.1200/JCO.2007.11.6053. Epub 2007 Oct 1.
Results Reference
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Analysis of T Cell Metabolism in Relapsed AML Patients With DLIs and Bicanorm Treatment
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