Isatuximab for Immune Cytopenia After Stem Cell Transplant

Recruiting at 6 trial locations

Overseen By Sergio Geralt, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: Corticosteroids, IVIG, Rituximab

Must not be taking: Anti-CD38 moAb

Disqualifiers: Relapse, Thrombotic microangiopathy, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Duration not specified

25 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to find out whether isatuximab is an effective treatment for people who developed immune cytopenias/ICs after allogeneic hematopoietic cell transplant/allo-HCT.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that growth factors like granulocyte colony stimulating factors and erythropoietin are allowed if administered at a stable dose. It's best to discuss your specific medications with the study team.

How is the drug Isatuximab different from other treatments for immune cytopenia after stem cell transplant?

Isatuximab is unique because it targets a different protein (CD38) on immune cells compared to Rituximab, which targets CD20. This difference in target proteins may offer an alternative approach for patients who do not respond well to existing treatments like Rituximab. ^{1 2 3 4 5}

Research Team

Michael Scorder, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults who have immune cytopenias after a stem cell transplant and haven't improved after at least two treatments, including steroids and rituximab. They must be in remission from the disease that required the transplant, not pregnant or willing to use birth control, free of active hepatitis or HIV, and able to give consent.

Inclusion Criteria

My condition didn't improve after trying at least 2 treatments including steroids, IVIG, or rituximab.

Patients with concomitant ICs can be enrolled on the study

Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L

Exclusion Criteria

I am able to understand and follow the study's requirements.

Pregnancy or unwillingness to agree to birth control

I am HIV positive or have an active hepatitis infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive isatuximab for treatment of refractory immune cytopenias after allo-HCT

Duration not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 4 years

Treatment Details

Interventions

• Isatuximab

Trial Overview The trial is testing Isatuximab's effectiveness for patients with persistent immune cytopenias following an allogeneic hematopoietic cell transplant. It aims to see if this drug can help where other treatments like corticosteroids have failed.

Participant Groups

Group I: Participants with Refractory Immune Cytopenias Experimental Treatment 1 Intervention

Participants will be adults who develop Immune Cytopenias/ICs after Allogeneic Hematopoietic Cell Transplantation/allo-HCT and who did not respond to initial immunosuppressive therapy.

Isatuximab is already approved in European Union, United States for the following indications:

Approved in European Union as Sarclisa for:

• Multiple myeloma

Approved in United States as Sarclisa for:

• Multiple myeloma in combination with pomalidomide and dexamethasone for adults who have received at least two prior therapies including lenalidomide and a proteasome inhibitor
• Multiple myeloma in combination with carfilzomib and dexamethasone for adults with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy
• Newly diagnosed multiple myeloma in combination with bortezomib, lenalidomide, and dexamethasone for adults who are not eligible for autologous stem cell transplant

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Sanofi

Industry Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Findings from Research

Rituximab was effective in treating autoimmune haemolytic anaemia (AIHA) and immune thrombocytopenia (ITP) in four patients after allogeneic stem cell transplantation, showing complete responses after conventional treatments failed.

This study suggests that autoimmune cytopenias, which were previously associated mainly with myeloablative conditioning, can also occur after reduced-intensity conditioning (RIC) regimens, indicating a need for awareness and better management strategies in these cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab is effective in the management of refractory autoimmune cytopenias occurring after allogeneic stem cell transplantation. Raj, K., Narayanan, S., Augustson, B., et al.[2015]

Rituximab, an anti-CD20 monoclonal antibody used for treating B-cell non-Hodgkin's lymphoma, has been associated with late-onset neutropenia, a condition where there is a dangerously low level of neutrophils, which are crucial for fighting infections.

This report highlights six cases of late-onset neutropenia occurring after stem cell transplantation, emphasizing the need for awareness and monitoring of this potential complication in patients receiving rituximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab-related late-onset neutropenia after autologous stem cell transplantation for aggressive non-Hodgkin's lymphoma. Lemieux, B., Tartas, S., Traulle, C., et al.[2015]

In a patient with late-onset neutropenia (LON) after rituximab treatment, the condition was linked to a lack of granulopoiesis in the bone marrow, rather than the presence of anti-neutrophil antibodies or other common causes of neutropenia.

High levels of BAFF (B-cell activating factor) were found, suggesting that excessive B-cell recovery may compete with granulocyte production in the bone marrow, indicating that monitoring BAFF levels could help identify patients at risk for developing LON.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Late-onset neutropenia following rituximab results from a hematopoietic lineage competition due to an excessive BAFF-induced B-cell recovery. Terrier, B., Ittah, M., Tourneur, L., et al.[2020]

In a study of 14 patients with follicular or mantle-cell lymphoma, a high incidence of neutropenia was observed in those treated with rituximab before and after autologous stem cell transplantation (ASCT).

The findings highlight the potential safety concern of neutropenia associated with rituximab treatment in the context of high-dose therapy and stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High incidence of neutropenia in patients treated with rituximab after autologous stem cell transplantation. Cairoli, R., Grillo, G., Tedeschi, A., et al.[2015]

Rituximab, a monoclonal anti-CD20 antibody, has been successfully used to treat refractory autoimmune hemolytic anemia (AIHA) in a child following allogeneic nonmyeloablative bone marrow transplantation, indicating its potential efficacy in this context.

AIHA can develop after hematopoietic stem cell transplantation and may be linked to other blood cell deficiencies, highlighting the importance of effective treatment options like rituximab for managing such complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful treatment of refractory autoimmune hemolytic anemia with monthly rituximab following nonmyeloablative stem cell transplantation for sickle cell disease. Raj, A., Bertolone, S., Cheerva, A.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Rituximab is effective in the management of refractory autoimmune cytopenias occurring after allogeneic stem cell transplantation. [2015]

2. England pubmed.ncbi.nlm.nih.gov

Rituximab-related late-onset neutropenia after autologous stem cell transplantation for aggressive non-Hodgkin's lymphoma. [2015]

3. Italy pubmed.ncbi.nlm.nih.gov

Late-onset neutropenia following rituximab results from a hematopoietic lineage competition due to an excessive BAFF-induced B-cell recovery. [2020]

4. Italy pubmed.ncbi.nlm.nih.gov

High incidence of neutropenia in patients treated with rituximab after autologous stem cell transplantation. [2015]

5. United States pubmed.ncbi.nlm.nih.gov

Successful treatment of refractory autoimmune hemolytic anemia with monthly rituximab following nonmyeloablative stem cell transplantation for sickle cell disease. [2019]