CART TreatmentPhase 2NCT05286164
Eltrombopag Treatment in Patients With Prolonged BM Toxicity After CART
A Phase 2 study testing Eltrombopag in people with CART Treatment and B Cell Lymphoma, run by Tel-Aviv Sourasky Medical Center at 1 site in Israel.
Trial summary
Treatment with chimeric antigen receptor-T cell (CAR-T) is successful in patients who have not responded to chemotherapy or bone marrow transplantation but it may provoke side effects and long-term complications. Early and specific side effects include cytokine release syndrome and neurological toxicity. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- CART Treatment, B Cell Lymphoma
- What is being tested?
- Eltrombopag
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteIsrael
- Study dates
- Apr 2022to Apr 2024
- Phase
- Phase 2
- 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
- Willing to participate in the study and able to sign an informed consent form.
- Patients with B cell lymphoma or multiple myeloma who were treated with CART and demonstrated cytopenia on day 14 after CART administration. Cytopenia definition: absolute neutrophil count <500 neutrophils/ul and/or platelets <50,000 mm3
- Bone marrow demonstrates hypoplasia (cellularity less than 30%) 14 days after CART administration.
- -
Who cannot join
- Creatine > 2.5 mg / dL
- Disorder in liver enzymes: bilirubin above 2 mg/dl , AST or ALT 5 times the normal.
- Active infection
- Active hemophagocytic syndrome
- Evidence of a viral or pharmacological disease that causes bone marrow injury
- Susceptibility to eltrombopag
- Evidence of disease in the bone marrow -
Trial locations and contacts
1 site in 1 country.
Israel1 site, 1 recruiting
- Recruiting
Tel-Aviv Sourasky Medicak center / BMT Unit
Tel Aviv, 6423906
Ron Ram, MD, +972-3-6974138, ronr@tlvmc.gov.il
About this study
Official title: Eltrombopag Treatment and Analysis of Bone Marrow Environment in Patients With Prolonged Bone Marrow Toxicity After CART Treatment
Treatment with chimeric antigen receptor-T cell (CAR-T) is successful in patients who have not responded to chemotherapy or bone marrow transplantation but it may provoke side effects and long-term complications. Early and specific side effects include cytokine release syndrome and neurological toxicity. In addition, there are also late side effects. The most prominent of which is bone marrow damage and lack of recovery of blood counts after treatment.
In this study, patients with prolong aplasia after CAR-T will recieve eltrombopag to enahnce bone marrow recovery.
Read the detailed description
CAR-T therapy is the standrad of care in patients with relapse/refractory B cell agressive lymphoproliferative diseases. Prolonged cytopenia is a not uncommon side effect and is associated with susbstantial morbidity and in severe cases also with mortality. The pathobiologic process that causes bone marrow injury is not known and in order to find appropriate treatment it is important to expand the knowledge regarding this toxicity. Current treatment options for bone marrow suppression includes growth factor therapy (GCSF), steroids and immunoglobulins. .
The investigators hypothesize that CART cells directly suppress or create inflammatory process in bone marrow. This process may resemble aplastic anemia, a marrow aplasia that occurs secondary to inflammatory process.
Treatment of aplastic anemia is based on the administration of eltrombopag, that causes a thrombopoietin-mimetic blood cells to develop and multiply. This treatment demonstrated an increase in the amount of platelets and neutrophils in patients with aplastic anemia and is approved by the health authorities around the world and in Israel as a standard treatment for this disease. There are several reports of successful use of altrombopag in patients after CART who have developed marrow toxicity and in patients after bone marrow transplantation whose blood counts are low.
In this study, patients with prologed aplasia after CART cells therapy, will be given eltrombopag in a purpose to incrase bone marrow function. In addition, the investigators will perform several assays to shed more light on the basic pathologic process that causes the bone marrow aplasia.
- Conditions
- CART Treatment, B Cell Lymphoma
- Being tested
- Eltrombopag
- Medical subject headings
- Lymphoma, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EltrombopagDrug
Eltrombopag 150 mg QD for 8 weeks
| Study group | Role | What they receive |
|---|---|---|
| Eltrombopag | Experimental | Patients with bone marrow aplasia for more than 30 days after CART treatment Receives: Drug: Eltrombopag |
What is being measured
The primary outcome is the main question the study is designed to answer.
The percentage of cellularity
Efficacy of eltrombopag treatment will be measured based on recovery of blood counts and recovery of bone marrow aplasia (measured as percentage of cellularity)
Measured: up to 12 weeks (4 weeks from CART treatment and additional 8 weeks of treatment with eltrombopag)
Identify the mechanism for the appearance of late bone marrow toxicity
Identification of the mechanism for the CART- associated bone marrow aplasia will be based on cytokines profile, T cell subclasses analyses and single cell RNA sequencing. This will enable the investigators to shed more light on the pathologic process that connects CART cells admisnitration and bone marrow apasia.
Measured: 12 weeks from CART treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2022
- Study startApr 2022 (estimated)
- Primary completionApr 2023 (estimated)
- Study completionApr 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CART TreatmentStudies of the same condition, open and under way.
- More trials run by Tel-Aviv Sourasky Medical CenterThe sponsor's other registered studies.
- 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
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Patients with bone marrow aplasia for more than 3 weeks after CART administration will receive eltrombopag treatment at a dose of 150 mg for 8 weeks.
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tel-Aviv Sourasky Medical Center
- Sponsor type
- Other government
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Ron Ram, Prof., Principal investigator, Sourasky Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05286164
- Sponsor's protocol ID
- 0248-21
- Status last verified
- Mar 2022
- First submitted
- 24 Feb 2022
- Last updated
- 15 Apr 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Eltrombopag Treatment and Analysis of Bone Marrow Environment in Patients With Prolonged Bone Marrow Toxicity After CART Treatment
- ClinicalTrials.gov ID
- NCT05286164
- Acronym / sponsor ID
- 0248-21
- Conditions
- CART Treatment, B Cell Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Tel-Aviv Sourasky Medical CenterOther government
- Collaborators
- Novartis
- Study start
- Apr 2022 (estimated)
- Primary completion
- Apr 2023 (estimated)
- Study completion
- Apr 2024 (estimated)
- First posted
- 18 Mar 2022 (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.
Treatment with chimeric antigen receptor-T cell (CAR-T) is successful in patients who have not responded to chemotherapy or bone marrow transplantation but it may provoke side effects and long-term complications. Early and specific side effects include cytokine release syndrome and neurological toxicity. In addition, there are also late side effects. The most prominent of which is bone marrow damage and lack of recovery of blood counts after treatment.
In this study, patients with prolong aplasia after CAR-T will recieve eltrombopag to enahnce bone marrow recovery.
Detailed description
CAR-T therapy is the standrad of care in patients with relapse/refractory B cell agressive lymphoproliferative diseases. Prolonged cytopenia is a not uncommon side effect and is associated with susbstantial morbidity and in severe cases also with mortality. The pathobiologic process that causes bone marrow injury is not known and in order to find appropriate treatment it is important to expand the knowledge regarding this toxicity. Current treatment options for bone marrow suppression includes growth factor therapy (GCSF), steroids and immunoglobulins. .
The investigators hypothesize that CART cells directly suppress or create inflammatory process in bone marrow. This process may resemble aplastic anemia, a marrow aplasia that occurs secondary to inflammatory process.
Treatment of aplastic anemia is based on the administration of eltrombopag, that causes a thrombopoietin-mimetic blood cells to develop and multiply. This treatment demonstrated an increase in the amount of platelets and neutrophils in patients with aplastic anemia and is approved by the health authorities around the world and in Israel as a standard treatment for this disease. There are several reports of successful use of altrombopag in patients after CART who have developed marrow toxicity and in patients after bone marrow transplantation whose blood counts are low.
In this study, patients with prologed aplasia after CART cells therapy, will be given eltrombopag in a purpose to incrase bone marrow function. In addition, the investigators will perform several assays to shed more light on the basic pathologic process that causes the bone marrow aplasia.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Patients with bone marrow aplasia for more than 3 weeks after CART administration will receive eltrombopag treatment at a dose of 150 mg for 8 weeks.
| Arm | Type | Receives |
|---|---|---|
| Eltrombopag | Experimental | Drug: EltrombopagPatients with bone marrow aplasia for more than 30 days after CART treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Willing to participate in the study and able to sign an informed consent form.
- Patients with B cell lymphoma or multiple myeloma who were treated with CART and demonstrated cytopenia on day 14 after CART administration. Cytopenia definition: absolute neutrophil count <500 neutrophils/ul and/or platelets <50,000 mm3
- Bone marrow demonstrates hypoplasia (cellularity less than 30%) 14 days after CART administration.
- -
Key exclusion criteria (7 listed)
- Creatine > 2.5 mg / dL
- Disorder in liver enzymes: bilirubin above 2 mg/dl , AST or ALT 5 times the normal.
- Active infection
- Active hemophagocytic syndrome
- Evidence of a viral or pharmacological disease that causes bone marrow injury
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 |
|---|---|---|
| EltrombopagEltrombopag 150 mg QD for 8 weeks | Drug | Eltrombopag |
Primary outcome
The percentage of cellularity
Time frame: up to 12 weeks (4 weeks from CART treatment and additional 8 weeks of treatment with eltrombopag)
Efficacy of eltrombopag treatment will be measured based on recovery of blood counts and recovery of bone marrow aplasia (measured as percentage of cellularity)
Identify the mechanism for the appearance of late bone marrow toxicity
Time frame: 12 weeks from CART treatment
Identification of the mechanism for the CART- associated bone marrow aplasia will be based on cytokines profile, T cell subclasses analyses and single cell RNA sequencing. This will enable the investigators to shed more light on the pathologic process that connects CART cells admisnitration and bone marrow apasia.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2022.
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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.
Ron Ram, Prof. principal investigator
Sourasky Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Eltrombopag in people with CART Treatment and B Cell Lymphoma, run by Tel-Aviv Sourasky Medical Center at 1 site in Israel.
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 4 inclusion and 7 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: status not confirmed, as of the sponsor's last update on 15 Apr 2022. 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 Israel. 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?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ron Ram, Prof. (972-3-6947830 ext. 7830, ronr@tlvmc.gov.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The percentage of cellularity (time frame: up to 12 weeks (4 weeks from CART treatment and additional 8 weeks of treatment with eltrombopag)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Apr 2022.