Clinical trial NCT04321161: 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
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Acute Myeloid Leukemia, in Relapse
Lead sponsor: University of Freiburg
Sponsor class: OTHER
First posted: 2020-03-25
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: T cell glycolytic activity
timeFrame: 2 months
measure: T cell respiratory activity
timeFrame: 2 months
measure: T cell phenotype
timeFrame: 2 months
Secondary outcomes:
measure: Serum pH
timeFrame: 2 months
Other outcomes:
Locations:
city: Freiburg
country: Germany
facility: Medical Center University of Freiburg
state: Baden-Württemberg
Study officials:
affiliation: Medical Center University of Freiburg
name: Robert Zeiser, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.