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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether isatuximab, a monoclonal antibody, can treat immune cytopenias, blood disorders that may occur after a stem cell transplant. The study targets individuals who did not respond well to initial treatments for these disorders. It suits those who have undergone a stem cell transplant, are beyond the initial recovery phase, and continue to experience low blood cell counts despite previous treatments. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that isatuximab is likely to be safe for humans?

Research shows that isatuximab is generally well-tolerated. In studies with patients who have multiple myeloma, treatments using isatuximab mostly resulted in mild and manageable side effects. Most side effects were not severe and could be controlled. Importantly, no new safety issues emerged.

More side effects were reported in the isatuximab group compared to the control group, with 1,135 side effects versus 906 in the control group. However, these side effects were usually not serious.

The FDA has approved isatuximab for treating multiple myeloma, indicating it meets safety standards for that condition. While multiple myeloma differs from immune cytopenias, this approval suggests a level of safety confidence in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Isatuximab is unique because it specifically targets CD38, a protein found on immune cells that are often involved in immune cytopenias after stem cell transplants. Unlike traditional treatments, which typically involve broad immunosuppressive therapy, isatuximab offers a more targeted approach, potentially reducing unwanted side effects. Researchers are excited about isatuximab because it promises a new mechanism of action that could be more effective for patients who don't respond to standard immunosuppressive treatments.

What evidence suggests that isatuximab might be an effective treatment for immune cytopenias?

Research has shown that isatuximab, the investigational treatment in this trial, can help treat immune cytopenias, particularly in patients unresponsive to other treatments. Studies have found that isatuximab, often used for multiple myeloma, can significantly improve treatment outcomes. It targets and destroys specific immune cells that cause problems. Strong evidence supports its effectiveness, even for patients who have tried similar medications without success. Overall, the data suggests that isatuximab could be a promising option for managing immune cytopenias after stem cell transplants. ^{6 7 8 9 10}

Who Is on the Research Team?

Michael Scorder, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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 must have previously had documented primary neutrophil and platelet engraftment

Patients with concomitant ICs can be enrolled on the study

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT01084252

Study Details | NCT01084252 | Phase 1/2 Dose Escalation ... Data for this outcome measure was planned to be collected and analyzed separately for dose 0.3 mg/kg, 1 mg/kg and not for 0.0001, 0.001, 0.01, 0.03 and 0.1 dose ...

2. trialx.com trialx.com/clinical-trials/listings/242931/open-label-phase-ii-trial-of-isatuximab-for-patients-with-refractory-immune-cytopenias-after-allogeneic-hematopoietic-cell-transplantation/?&radius=50

Open-Label, Phase II Trial of Isatuximab for Patients With ... The purpose of this study is to find out whether isatuximab is an effective treatment for people who developed immune cytopenias/ICs after allogeneic ...

3. ancora.ai ancora.ai/fr/details/NCT05873205

Open-Label, Phase II Trial of Isatuximab for Patients With ... The purpose of this study is to find out whether isatuximab is an effective treatment for people who developed immune cytopenias/ICs after allogeneic hemat.

4. mdpi.com mdpi.com/2072-6694/17/21/3494

Efficacy and Safety of Isatuximab Combination Therapy in ... In conclusion, this meta-analysis provides consolidated, high-quality evidence that isatuximab significantly improves key efficacy outcomes, including PFS and ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12335847/

From the Pan-Pacific Multiple Myeloma Working Group Notably, efficacy was observed regardless of prior daratumumab exposure duration or timing, suggesting that Isa-Pd remains a viable option ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11685498/

Comprehensive safety evaluation of isatuximab in multiple ... The isatuximab therapy was associated with a total of 1135 AEs (Table 4), compared to 906 AEs reported in the control group. Within the ...

7. sarclisa.com sarclisa.com/newly-diagnosed-trial-results

Newly Diagnosed Trial Results At a median follow-up of 60 months, 75% (198 out of 265 patients) treated with SARCLISA + VRd achieved complete response or better vs 64% (116 out of 181 ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT01084252

Study Details | NCT01084252 | Phase 1/2 Dose Escalation ... Data for this outcome measure was planned to be collected and analyzed separately for dose 0.3 mg/kg, 1 mg/kg and not for 0.0001, 0.001, 0.01, 0.03 and 0.1 dose ...

9. myeloma.org myeloma.org/sarclisa-isatuximab-irfc

Sarclisa (isatuximab-irfc) The FDA approval of Sarclisa in 2020 was based on data from the ICARIA-MM phase III clinical trial. This trial compared Isa-Pd to Pd alone. The study included ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8497289/

Isatuximab: A Review of Its Use in Multiple Myeloma - PMC Isatuximab-based combination therapies were generally well tolerated and demonstrated a manageable safety profile with no new safety signals. Although mature ...