Isatuximab for Immune Cytopenia After Stem Cell Transplant

Recruiting in Palo Alto (17 mi)

+6 other locations

Overseen by Michael Scorder, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Prior Safety Data

Approved in 2 Jurisdictions

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.

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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.

Trial 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

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Memorial Sloan Kettering Nassau (All protocol activities) Rockville Centre, NY

Memorial Sloan Kettering Westchester (Limited Protocol Activities) Harrison, NY

Memorial Sloan Kettering Cancer Center (All Protocol Activities) New York, NY

Memorial Sloan Kettering Bergen (Limited protocol activities) Montvale, NJ

More Trial Locations

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center Lead Sponsor

Sanofi Industry Sponsor

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] Autoimmune haemolytic anaemia (AIHA), immune thrombocytopenia (ITP) and autoimmune neutropenia (AIN) are well-recognised complications of allogeneic stem cell transplantation (SCT), but have previously only been reported in the context of myeloablative conditioning regimens. Management of AIHA, ITP or AIN occurring after allogeneic SCT is unsatisfactory since they frequently prove refractory to conventional therapies including splenectomy. As a consequence, autoimmune cytopenias occurring after allogeneic SCT are associated with substantial morbidity and mortality. We report four patients who developed AIHA or ITP after allogeneic transplantation -- three of which occurred after a reduced-intensity conditioning (RIC) regimen. All patients demonstrated a complete response to Rituximab, having failed to respond to conventional treatment including high-dose prednisolone and intravenous immunoglobulin (IVIg). We conclude that Rituximab can be a valuable agent in the management of autoimmune cytopenias occurring after allogeneic SCT and that autoimmune cytopenias may be a hitherto unrecognised complication of RIC regimens.

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

Rituximab-related late-onset neutropenia after autologous stem cell transplantation for aggressive non-Hodgkin's lymphoma. [2015] Rituximab, an anti-CD20 monoclonal antibody, is increasingly used in the treatment of B-cell non-Hodgkin's lymphoma. Late-onset neutropenia in relation to rituximab has been recently described. In this report, we present six cases occurring after stem cell transplantation and discuss the potential impact of this complication.

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] Rituximab is used in the treatment of lymphoma and autoimmune diseases, for which late-onset neutropenia (LON) were reported. LON-related mechanisms remain unclear. To obtain insights into the mechanisms, we assessed serum, peripheral blood and bone marrow (BM) samples of a patient with LON. Factors classically associated with neutropenia such as anti-neutrophil antibodies, T-LGL, soluble Fas Ligand were not detectable. We then evaluated the kinetics of various cytokines involved in B-cell and granulocyte homeostasis. We found that LON is related to a lack of granulopoiesis in the BM that coincides with a very high level of BAFF, a strong stimulator of B-cell recovery, and hypothesized a hematopoietic lineage competition due to an excessive B-cell recovery in the BM by promotion of B-cell lymphopoiesis over granulopoiesis within common developmental niches. Assessment of serum BAFF levels following rituximab could detect patients at risk of developing LON.

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

High incidence of neutropenia in patients treated with rituximab after autologous stem cell transplantation. [2015] We report a high incidence of neutropenia in patients treated with rituximab prior to and following autologous stem cell transplantation (ASCT). Fourteen patients with follicular or mantle-cell lymphoma were treated with high dose (HD) therapy followed by an in vivo-purged autologous graft.

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] Autoimmune hemolytic anemia (AIHA) can occur following hematopoietic stem cell transplantation (HSCT) and may be associated with other cytopenias. It can also occur in the context of chronic red cell transfusion in patients maintained on hypertransfusion regimens. There are an increasing number of reports on the successful treatment of autoimmune cytopenias with the monoclonal anti-CD20 antibody rituximab, including a few patients in a post-HSCT setting. The authors report the successful treatment with rituximab of refractory AIHA following allogeneic nonmyeloablative bone marrow transplantation in a child with sickle cell disease.