Rapcabtagene Autoleucel for Systemic Sclerosis

Recruiting in Palo Alto (17 mi)

+15 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Novartis Pharmaceuticals

Disqualifiers: Pulmonary hypertension, Renal pathology, Hypertension, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the efficacy, safety and tolerability of rapcabtagene autoleucel (administered once following lymphodepletion) in participants with severe refractory diffuse cutaneous systemic sclerosis relative to rituximab.

Do I need to stop my current medications to join the trial?

The trial mentions a 'washout period' (time without taking certain medications) as part of the protocol, so you may need to stop some medications. However, the specific medications that need to be stopped are not detailed in the provided information.

What data supports the effectiveness of the treatment Rapcabtagene Autoleucel for systemic sclerosis?

Research on similar treatments, like rituximab, shows that it can help improve skin and lung issues in systemic sclerosis, suggesting potential benefits for Rapcabtagene Autoleucel. Additionally, stem cell transplantation, which involves a similar approach of resetting the immune system, has shown significant improvement in skin and organ involvement in systemic sclerosis patients. ^{1 2 3 4 5}

What is the safety profile of anti-CD19 CAR T-cell therapies?

Anti-CD19 CAR T-cell therapies, like axicabtagene ciloleucel and brexucabtagene autoleucel, have shown high effectiveness in treating certain blood cancers but can cause serious side effects, including cytokine release syndrome (a severe immune reaction) and neurologic toxicities (problems with the nervous system). These side effects can be severe and need special medical care. ^{6 7 8 9 10}

How is the treatment Rapcabtagene Autoleucel for Systemic Sclerosis different from other treatments?

Rapcabtagene Autoleucel is a type of CAR-T cell therapy, which involves modifying a patient's own immune cells to better target and attack disease cells. This approach is unique compared to traditional treatments for systemic sclerosis, as it uses the body's immune system in a highly targeted way, which is more commonly used in certain types of blood cancers. ^{8 9 10 11 12}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

This trial is for individuals with severe refractory diffuse cutaneous systemic sclerosis, a type of scleroderma affecting the skin and sometimes internal organs. Specific eligibility criteria are not provided, but typically participants must meet certain health standards to be included.

Inclusion Criteria

My first symptoms of scleroderma appeared less than 7 years ago.

My condition involves severe lung, skin, or heart issues due to systemic sclerosis.

Participant must fulfill the 2013 American College of Rheumatology/ European League Against Rheumatism classification criteria for systemic sclerosis and meet the diffuse cutaneous SSc (dcSSc) subset classification according to LeRoy

Exclusion Criteria

Any participant for whom treatment with rituximab is clinically inappropriate in the opinion of the investigator

Any medical conditions that are not related to SSc that, in the opinion of the Investigator, would jeopardize the ability of the participant to tolerate lymphodepletion and anti-CD19 CAR-T cell therapy

Any condition during Screening that could prevent a complete washout of medications as required per protocol or could otherwise make the participant ineligible for anti-CD19 CAR-T therapy and further participation in the study, as judged by the Investigator

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive rapcabtagene autoleucel or rituximab, with rapcabtagene autoleucel administered once following lymphodepletion

52 weeks

Regular visits for assessment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments including FVC% and mRSS

104 weeks

Long-term follow-up

Participants who received rapcabtagene autoleucel enter a long-term follow-up period lasting up to 15 years

Treatment Details

Interventions

• Rapcabtagene Autoleucel (CAR T-cell Therapy)
• Rituximab (Monoclonal Antibodies)

Trial Overview The study is testing rapcabtagene autoleucel, given once after preparing the body's immune system (lymphodepletion), against rituximab to see which is more effective and safe for treating severe systemic sclerosis.

Participant Groups

Group I: rapcabtagene autoleucel arm Experimental Treatment 1 Intervention

rapcabtagene autoleucel

Group II: rituximab arm Active Control 1 Intervention

rituximab

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Findings from Research

In an observational study of 8 patients with refractory systemic sclerosis (SSc)-associated calcinosis treated with rituximab (RTX), 50% experienced significant clinical improvement, including reduced pain and no new episodes of inflammation or skin ulceration.

Rituximab showed a low incidence of adverse effects, with only one patient (12.5%) developing mild upper respiratory infections, suggesting it may be a safe option for treating severe cases of calcinosis in SSc.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of rituximab for the treatment of refractory systemic sclerosis associated calcinosis: A case series and systematic review of the literature. Narváez, J., Pirola, JP., LLuch, J., et al.[2020]

Rituximab (RTX) was found to be effective in treating systemic sclerosis (SSc), particularly in patients with early and rapidly progressive forms of the disease, as evidenced by stabilization of pulmonary symptoms and improvement in skin scores after treatment.

The study included 10 patients with diffuse SSc, showing that even those with long-term illness may experience benefits from RTX, supporting its use as a potential treatment option for this challenging autoimmune disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab for the therapy of systemic sclerosis: a series of 10 cases in a single center. Vilela, VS., Maretti, GB., Gama, LM., et al.[2018]

In an open-label study of 8 patients with early diffuse systemic sclerosis (dcSSc), a two-treatment course of rituximab (RTX) significantly improved skin scores and reduced disease activity over 24 months, indicating potential efficacy for managing skin disease.

The treatment was well tolerated, with no serious adverse events linked to RTX, and it effectively depleted B cells, suggesting a mechanism of action that may contribute to the observed clinical improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-year results of an open pilot study of a 2-treatment course with rituximab in patients with early systemic sclerosis with diffuse skin involvement. Smith, V., Piette, Y., van Praet, JT., et al.[2015]

Equecabtagene autoleucel (Fucaso®) is a CAR-T cell therapy specifically designed to target B cell maturation antigen (BCMA) and has been conditionally approved in China for treating adults with relapsed or refractory multiple myeloma (RRMM) after at least three prior therapies.

This therapy represents a significant advancement in treatment options for RRMM patients, particularly those who have not responded to other treatments, highlighting its potential efficacy in a challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Equecabtagene Autoleucel: First Approval. Keam, SJ.[2023]

In the updated ZUMA-3 study with a median follow-up of 26.8 months, brexucabtagene autoleucel (KTE-X19) achieved a 71% complete remission rate in adults with relapsed or refractory B-precursor acute lymphoblastic leukemia, indicating its efficacy as a treatment option.

Patients treated with KTE-X19 had a median overall survival of 25.4 months, significantly longer than the 5.5 months observed in matched historical controls, demonstrating a meaningful survival benefit with manageable safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-year follow-up of KTE-X19 in patients with relapsed or refractory adult B-cell acute lymphoblastic leukemia in ZUMA-3 and its contextualization with SCHOLAR-3, an external historical control study. Shah, BD., Ghobadi, A., Oluwole, OO., et al.[2023]

The three CAR-T cell therapies (axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel) show promising efficacy in treating large B cell lymphoma, with overall response rates of nearly 70% and complete response rates exceeding 50% across 33 studies involving 2,172 patients.

However, axicabtagene ciloleucel and tisagenlecleucel are associated with significant risks of severe neurotoxicity and life-threatening cytokine release syndrome, necessitating careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of CAR-T Cell Products Axicabtagene Ciloleucel, Tisagenlecleucel, and Lisocabtagene Maraleucel for the Treatment of Hematologic Malignancies: A Systematic Review and Meta-Analysis. Meng, J., Wu, X., Sun, Z., et al.[2022]

CAR-T therapies, specifically idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), show significant potential in treating heavily pretreated relapsed/refractory multiple myeloma (RRMM), with updated clinical trial data indicating they can elicit responses in these patients.

Indirect comparisons suggest that cilta-cel may provide deeper and more durable responses than ide-cel in patients with triple class-exposed RRMM, although direct head-to-head trials are necessary to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent Advances in the Use of Chimeric Antigen Receptor-Expressing T-Cell Therapies for Treatment of Multiple Myeloma. Martin, T., Jackson, CC., Pacaud, L., et al.[2023]

Chimeric antigen receptor (CAR) T-cell therapy, such as tisagenlecleucel (Kymriah) and axicabtagene ciloleucel (Yescarta), is an effective treatment for relapsed/refractory B-cell acute lymphoblastic leukemia and diffuse large B-cell lymphoma, utilizing genetically modified T-cells that target the CD19 antigen.

This collaborative work provides practical guidance for healthcare centers on how to select patients for these commercially available CAR T-cell therapies, ensuring appropriate use and maximizing treatment benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Eligibility of patients for CAR T-cell: Expert opinion-based collaborative work by the SFGM-TC]. Beauvais, D., Bachy, E., Baruchel, A., et al.[2021]

References

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

Haematopoietic stem cell transplantation for the treatment of systemic sclerosis and other autoimmune disorders. [2019]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of rituximab for the treatment of refractory systemic sclerosis associated calcinosis: A case series and systematic review of the literature. [2020]

3. Brazil pubmed.ncbi.nlm.nih.gov

Rituximab for the therapy of systemic sclerosis: a series of 10 cases in a single center. [2018]

4. Canada pubmed.ncbi.nlm.nih.gov

Two-year results of an open pilot study of a 2-treatment course with rituximab in patients with early systemic sclerosis with diffuse skin involvement. [2015]

5. Italy pubmed.ncbi.nlm.nih.gov

Effect of long-term treatment with rituximab on pulmonary function and skin fibrosis in patients with diffuse systemic sclerosis. [2017]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Equecabtagene Autoleucel: First Approval. [2023]

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

CAR T-cell therapy for B-cell lymphoma. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Axicabtagene ciloleucel and brexucabtagene autoleucel in relapsed and refractory diffuse large B-cell and mantle cell lymphomas. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Two-year follow-up of KTE-X19 in patients with relapsed or refractory adult B-cell acute lymphoblastic leukemia in ZUMA-3 and its contextualization with SCHOLAR-3, an external historical control study. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of CAR-T Cell Products Axicabtagene Ciloleucel, Tisagenlecleucel, and Lisocabtagene Maraleucel for the Treatment of Hematologic Malignancies: A Systematic Review and Meta-Analysis. [2022]

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

Recent Advances in the Use of Chimeric Antigen Receptor-Expressing T-Cell Therapies for Treatment of Multiple Myeloma. [2023]

12. France pubmed.ncbi.nlm.nih.gov

[Eligibility of patients for CAR T-cell: Expert opinion-based collaborative work by the SFGM-TC]. [2021]