Eltrombopag Treatment in Patients With Prolonged BM Toxicity After CART

NCT ID: NCT05286164

Last Updated: 2022-04-15

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-30
• Study Completion Date: 2024-04-30

Brief 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. 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.

Conditions

CART Treatment; B Cell Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Eltrombopag

Patients with bone marrow aplasia for more than 30 days after CART treatment

Group Type: EXPERIMENTAL

Eltrombopag

Intervention Type: DRUG

Eltrombopag 150 mg QD for 8 weeks

Interventions

Eltrombopag

Eltrombopag 150 mg QD for 8 weeks

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Willing to participate in the study and able to sign an informed consent form.

2. 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

3. Bone marrow demonstrates hypoplasia (cellularity less than 30%) 14 days after CART administration.

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Exclusion Criteria

1. Creatine > 2.5 mg / dL

2. Disorder in liver enzymes: bilirubin above 2 mg/dl , AST or ALT 5 times the normal.

3. Active infection

4. Active hemophagocytic syndrome

5. Evidence of a viral or pharmacological disease that causes bone marrow injury

6. Susceptibility to eltrombopag

7. Evidence of disease in the bone marrow -

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis

INDUSTRY

Sponsor Role: collaborator

Tel-Aviv Sourasky Medical Center

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ron Ram, Prof.

Role: PRINCIPAL_INVESTIGATOR

Sourasky Medical Center

Locations

Tel-Aviv Sourasky Medicak center / BMT Unit

Tel Aviv, , Israel

Site Status: RECRUITING

Countries

Israel

Central Contacts

Ron Ram, Prof.

Role: CONTACT

ronr@tlvmc.gov.il

972-3-6947830 ext. 7830

Facility Contacts

Ron Ram, MD

Role: primary

ronr@tlvmc.gov.il

+972-3-6974138

Other Identifiers

0248-21

Identifier Type: -

Identifier Source: org_study_id