Analysis of T Cell Metabolism in Relapsed AML Patients With DLIs and Bicanorm Treatment

Acute Myeloid Leukemia, in Relapse Clinical Trial

Official title:

Analysis of T Cell Metabolism and Immune Phenotype in Relapsed Acute Myeloid Leukemia Patients Receiving Donor Lymphocyte Infusions and Bicanorm (Sodium Bicarbonate)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04321161
• Other study ID #: BICARB_AMLrelapse
• Status: Completed
• Phase: Early Phase 1
• Start date: February 25, 2020
• Est. completion date: March 18, 2020

Study information

• Verified date: March 2020
• Source: University of Freiburg
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: March 18, 2020
• Est. primary completion date: March 18, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia, in Relapse
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Bicanorm
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)

Locations

Country	Name	City	State
Germany	Medical Center University of Freiburg	Freiburg	Baden-Württemberg

Sponsors (1)

Lead Sponsor	Collaborator
University of Freiburg

Country where clinical trial is conducted

Germany, 

References & Publications (3)

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. — View Citation

Pilon-Thomas S, Kodumudi KN, El-Kenawi AE, Russell S, Weber AM, Luddy K, Damaghi M, Wojtkowiak JW, Mulé 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. — View Citation

Schmid C, Labopin M, Nagler A, Bornhäuser M, Finke J, Fassas A, Volin L, Gürman 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. Epub 2007 Oct 1. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	T cell glycolytic activity	Extracellular acidification rate (ECAR) determined by live-cell metabolic assay using the Seahorse Analyzer	2 months
Primary	T cell respiratory activity	Oxygen consumption rate (OCR) determined by live-cell metabolic assay using the Seahorse Analyzer	2 months
Primary	T cell phenotype	T cell cytokine and effector molecule production determined by flow cytometric analysis	2 months
Secondary	Serum pH	Measurement of serum pH	2 months