Acute Myeloid Leukemia, in RelapseEarly Phase 1NCT04321161
Analysis of T Cell Metabolism in Relapsed AML Patients With DLIs and Bicanorm Treatment
A Early Phase 1 study testing Bicanorm in people with Acute Myeloid Leukemia, in Relapse, run by University of Freiburg at 1 site in Germany.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, in Relapse
- What is being tested?
- Bicanorm
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteGermany
- Study dates
- 25 Feb 2020to 18 Mar 2020
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- age < 18 years
- lack of informed consent
Trial locations and contacts
1 site in 1 country.
Germany1 site
Medical Center University of Freiburg
Freiburg im Breisgau, Baden-Wurttemberg, 79106
About this study
Official title: Analysis of T Cell Metabolism and Immune Phenotype in Relapsed Acute Myeloid Leukemia Patients Receiving Donor Lymphocyte Infusions and Bicanorm (Sodium Bicarbonate)
In this study, the outcomes of relapsed AML patients receiving DLIs and Bicanorm (Sodium bicarbonate) were analyzed including T cell metabolism and immune phenotype.
Read the 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.
- Conditions
- Acute Myeloid Leukemia, in Relapse
- Being tested
- Bicanorm
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BicanormDrug
Also called Sodium bicarbonate
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)
| Study group | Role | What they receive |
|---|---|---|
| AML relapse under DLI and Bicanorm treatment | Experimental | Analysis of T cell metabolism, immune phenotype and serum pH before and after Bicanorm (Sodium bicarbonate) treatment. Receives: Drug: Bicanorm |
What is being measured
The primary outcome is the main question the study is designed to answer.
T cell glycolytic activity
Extracellular acidification rate (ECAR) determined by live-cell metabolic assay using the Seahorse Analyzer
Measured: 2 months
T cell respiratory activity
Oxygen consumption rate (OCR) determined by live-cell metabolic assay using the Seahorse Analyzer
Measured: 2 months
T cell phenotype
T cell cytokine and effector molecule production determined by flow cytometric analysis
Measured: 2 months
Secondary outcomes (1)
Serum pH
Measurement of serum pH
Measured: 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2020
- Study start25 Feb 2020
- Primary completion18 Mar 2020
- Study completion18 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid Leukemia, in RelapseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Freiburg
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Robert Zeiser, University of Freiburg
- Investigators
- Robert Zeiser, Prof. Dr., Principal investigator, Medical Center University of Freiburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04321161
- Sponsor's protocol ID
- BICARB_AMLrelapse
- Status last verified
- Mar 2020
- First submitted
- 20 Mar 2020
- Last updated
- 25 Mar 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 26321679Pilon-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.
PubMed 26719539Schmid 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.
PubMed 17909197
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Analysis of T Cell Metabolism and Immune Phenotype in Relapsed Acute Myeloid Leukemia Patients Receiving Donor Lymphocyte Infusions and Bicanorm (Sodium Bicarbonate)
- ClinicalTrials.gov ID
- NCT04321161
- Acronym / sponsor ID
- BICARB_AMLrelapse
- Conditions
- Acute Myeloid Leukemia, in Relapse
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of FreiburgUniversity, hospital or other
- Study start
- 25 Feb 2020 (actual)
- Primary completion
- 18 Mar 2020 (actual)
- Study completion
- 18 Mar 2020 (actual)
- First posted
- 25 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AML relapse under DLI and Bicanorm treatment | Experimental | Drug: BicanormAnalysis of T cell metabolism, immune phenotype and serum pH before and after Bicanorm (Sodium bicarbonate) treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (2 listed)
- age < 18 years
- lack of informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BicanormAlso: Sodium bicarbonateTreatment 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) | Drug | AML relapse under DLI and Bicanorm treatment |
Primary outcome
T cell glycolytic activity
Time frame: 2 months
Extracellular acidification rate (ECAR) determined by live-cell metabolic assay using the Seahorse Analyzer
T cell respiratory activity
Time frame: 2 months
Oxygen consumption rate (OCR) determined by live-cell metabolic assay using the Seahorse Analyzer
T cell phenotype
Time frame: 2 months
T cell cytokine and effector molecule production determined by flow cytometric analysis
1 secondary outcome
Serum pH
Time frame: 2 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2020.
- Background: PubMed 26321679Chang 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.
- Background: PubMed 26719539Pilon-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.
- Background: PubMed 17909197Schmid 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert Zeiser, Prof. Dr. principal investigator
Medical Center University of Freiburg
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Bicanorm in people with Acute Myeloid Leukemia, in Relapse, run by University of Freiburg at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
T cell glycolytic activity (time frame: 2 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04321161, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Mar 2020.