Stem Cell Transplant for Autoimmune Neurological Diseases

Recruiting at 2 trial locations

Overseen By Leona Holmberg

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Fred Hutchinson Cancer Research Center

Disqualifiers: HIV, Pulmonary dysfunction, Heart failure, 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

Compensation: Varies

Number of Visits: 3

Duration: Approximately 3 weeks

53 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Anti-Thymocyte Globulin (ATG) for autoimmune neurological diseases?

Rabbit anti-thymocyte globulin, when combined with cyclosporine, has shown effectiveness in treating severe aplastic anemia, with response rates of 60-70% in patients. This suggests potential effectiveness in modulating the immune system, which could be beneficial for autoimmune neurological diseases. ^{1 2 3 4 5}

Is stem cell transplant with melphalan safe for humans?

Studies show that a new formulation of melphalan, called Evomela, used in stem cell transplants for multiple myeloma, has an acceptable safety profile. It avoids the use of propylene glycol, which can cause complications, and has shown no treatment-related deaths within 100 days post-transplant. ^{6 7 8 9 10}

How is the stem cell transplant treatment for autoimmune neurological diseases different from other treatments?

This treatment is unique because it uses a combination of high-dose chemotherapy and stem cell transplantation to 'reset' the immune system, potentially offering long-term remission for severe autoimmune diseases where other treatments have failed. It involves a specific regimen of drugs like Anti-Thymocyte Globulin and chemotherapy agents, which is not typical in standard treatments for these conditions. ^{11 12 13 14 15}

What is the purpose of this trial?

This trial tests a combination of strong chemotherapy and an immune-suppressing medicine followed by a stem cell transplant. It targets patients with autoimmune neurological diseases that haven't improved with other treatments. The treatment aims to weaken the immune system to stop it from attacking the nervous system and then helps the body recover by making new blood cells. High-dose chemotherapy followed by a stem cell transplant has been shown to improve various autoimmune diseases.

Research Team

Leona Holmberg

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

This trial is for patients under 70 with severe neurological autoimmune disorders like Multiple Sclerosis, Myasthenia Gravis, and others who haven't responded to at least two standard treatments. Donors must be a syngeneic sibling (like an identical twin) willing to undergo procedures for stem cell collection.

Inclusion Criteria

I have an autoimmune disorder affecting my nervous system.

I have been diagnosed with a severe neurological autoimmune disorder.

I have an autoimmune disorder affecting my nervous system.

Exclusion Criteria

There isn't enough evidence that the donor and recipient are a good genetic match.

I currently have an infection that isn't under control.

Donors who do not meet the requirements for donating blood as established by the institution.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive high-dose chemotherapy with carmustine, etoposide, cytarabine, melphalan, and antithymocyte globulin followed by autologous or syngeneic stem cell transplant

Approximately 3 weeks

Daily visits for chemotherapy administration

Post-Transplant Recovery

Patients receive prednisone and undergo recovery post-transplant

3 weeks

Regular monitoring visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Follow-up visits at 3 months, 1 year, and annually thereafter

Treatment Details

Interventions

• Anti-Thymocyte Globulin
• Carmustine
• Etoposide
• Melphalan

Trial Overview The study tests high-dose chemotherapy (carmustine, etoposide, cytarabine, melphalan) plus antithymocyte globulin followed by autologous stem cell transplant in treating autoimmune neurologic diseases that are resistant to other therapies.

Participant Groups

Group I: Treatment (immunosuppressive therapy followed by transplant) Experimental Treatment 10 Interventions

Patients receive carmustine IV on day -6, etoposide IV and cytarabine IV BID on days -5 to -2, melphalan IV on day -1 and antithymocyte globulin IV on days -2 and -1. Patients then undergo autologous or syngeneic stem cell transplant on day 0. Patients also receive prednisone PO QD on days 7-21, followed by 2 week taper.

Anti-Thymocyte Globulin is already approved in European Union, United States for the following indications:

Approved in European Union as Thymoglobulin for:

• Prevention and treatment of acute rejection following organ transplantation
• Severe aplastic anemia

Approved in United States as Thymoglobulin for:

• Prevention and treatment of acute rejection following kidney transplantation
• Severe aplastic anemia

Who Is Running the Clinical Trial?

Fred Hutchinson Cancer Research Center

Lead Sponsor

Trials

444

Recruited

148,000+

Fred Hutchinson Cancer Center

Lead Sponsor

Trials

583

Recruited

1,341,000+

Findings from Research

In a study involving 77 patients with Hodgkin's disease and non-Hodgkin's lymphoma, high-dose etoposide combined with either fractionated total body irradiation (TBI) or carmustine before autologous bone marrow transplantation showed promising results, with a 1-year survival rate of 85% for TBI patients and 79% for carmustine patients.

Despite the effectiveness, there was an 8% rate of toxic deaths, all occurring in the carmustine group, highlighting a safety concern associated with this treatment regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Stanford experience with high-dose etoposide cytoreductive regimens and autologous bone marrow transplantation in Hodgkin's disease and non-Hodgkin's lymphoma: preliminary data. Horning, SJ., Chao, NJ., Negrin, RS., et al.[2020]

In a phase II study involving 20 patients with severe aplastic anemia, rabbit anti-thymocyte globulin showed similar response rates to horse anti-thymocyte globulin, with no significant differences in efficacy or early mortality rates over 12 months.

Key predictors of treatment response included the presence of a paroxysmal nocturnal hemoglobinuria clone and a higher pretreatment reticulocyte count, while factors like younger age and higher neutrophil and lymphocyte counts were linked to better overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of rabbit anti-thymocyte globulin in severe aplastic anemia. Afable, MG., Shaik, M., Sugimoto, Y., et al.[2021]

EVOMELA, a new formulation of melphalan that is free from propylene glycol, has been shown to be safe and effective for high-dose conditioning in autologous stem cell transplantation for multiple myeloma, with a 100% overall response rate in a study of 61 patients.

The study reported low incidences of severe side effects, such as grade 3 mucositis (10%) and stomatitis (5%), indicating that EVOMELA has an acceptable safety profile compared to traditional formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase IIb, Multicenter, Open-Label, Safety, and Efficacy Study of High-Dose, Propylene Glycol-Free Melphalan Hydrochloride for Injection (EVOMELA) for Myeloablative Conditioning in Multiple Myeloma Patients Undergoing Autologous Transplantation. Hari, P., Aljitawi, OS., Arce-Lara, C., et al.[2017]

Evomela™, a propylene-free formulation of melphalan, offers improved stability and avoids the potential side effects associated with propylene glycol, making it a safer option for patients undergoing autologous stem cell transplantation for multiple myeloma.

The review highlights the pharmacokinetics and clinical data supporting the use of Evomela™ in myeloma treatment, indicating its effectiveness in ensuring proper dose delivery during transplantation procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Propylene glycol-free melphalan as conditioning regimen for autologous transplantation in myeloma. Aljitawi, OS., Hari, P.[2020]

References

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

The Stanford experience with high-dose etoposide cytoreductive regimens and autologous bone marrow transplantation in Hodgkin's disease and non-Hodgkin's lymphoma: preliminary data. [2020]

2. Italy pubmed.ncbi.nlm.nih.gov

Efficacy of rabbit anti-thymocyte globulin in severe aplastic anemia. [2021]

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

Immune hemolytic anemia following administration of antithymocyte globulin. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Apolipoprotein-A is a potential prognostic biomarker for severe aplastic anemia patients treated with ATG-based immunosuppressive therapy: a single-center retrospective study. [2022]

5. Iran pubmed.ncbi.nlm.nih.gov

Cutaneous finding in anti thymocyte globulin induced serum sickness. [2007]

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

A Phase IIb, Multicenter, Open-Label, Safety, and Efficacy Study of High-Dose, Propylene Glycol-Free Melphalan Hydrochloride for Injection (EVOMELA) for Myeloablative Conditioning in Multiple Myeloma Patients Undergoing Autologous Transplantation. [2017]

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

A triple-drug combination to prevent nausea and vomiting following BEAM chemotherapy before autologous hematopoietic stem cell transplantation. [2022]

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

Propylene glycol-free melphalan as conditioning regimen for autologous transplantation in myeloma. [2020]

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

A Review of Propylene Glycol-free Melphalan Conditioning for Hematopoietic Cell Transplantation for Multiple Myeloma and Light Chain Amyloidosis. [2023]

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

Phase III study of intermittent carmustine (BCNU), cyclophosphamide, and prednisone versus intermittent melphalan and prednisone in myeloma. [2013]

11. England pubmed.ncbi.nlm.nih.gov

Peripheral blood stem cell transplantation in the treatment of progressive multiple sclerosis: first results of a pilot study. [2022]

12. England pubmed.ncbi.nlm.nih.gov

A phase I-II trial of autologous peripheral blood stem cell transplantation in the treatment of refractory autoimmune disease. [2018]

13. Germany pubmed.ncbi.nlm.nih.gov

[Current value of stem-cell transplantation in autoimmune diseases]. [2021]

14. England pubmed.ncbi.nlm.nih.gov

Stem cell therapy for autoimmune disease: overview of concepts from the Snowbird 2002 tolerance and tissue regeneration meeting. [2004]

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

Autologous stem cell transplantation in autoimmune diseases. [2019]