Stem Cell Transplant for Autoimmune Neurological Diseases

Not currently recruiting at 2 trial locations

Overseen By James Bowen

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a chemotherapy drug combination, including Anti-Thymocyte Globulin (an immunosuppressive drug), followed by a stem cell transplant for individuals with autoimmune neurological diseases unresponsive to other treatments. Conditions like multiple sclerosis or myasthenia gravis involve the immune system mistakenly attacking the nervous system. The trial uses drugs to weaken the immune system before a transplant to halt these attacks. Suitable candidates have a severe autoimmune neurological disorder and have not responded to at least two different treatments. Participants must have a sibling who is an identical genetic match to provide stem cells for the transplant. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to benefit from innovative therapies.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the treatments under study have varying safety levels. Anti-thymocyte globulin, commonly used in kidney transplants, helps prevent rejection but can cause fever and chills. Carmustine, used in cancer treatment, may lead to nausea and low blood counts. Etoposide, another cancer treatment, might cause low blood pressure and hair loss. Melphalan, also used for cancer, can cause similar side effects, including nausea and low blood counts.

These drugs are generally well-tolerated in controlled settings. However, as this trial is in an early phase, researchers are closely monitoring safety and side effects. Participants should consult their doctors about potential risks before joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment because it offers a novel approach to tackling autoimmune neurological diseases. Unlike the standard treatments, which often include immunosuppressive drugs alone, this therapy combines immunosuppressive medications like anti-thymocyte globulin, carmustine, etoposide, and melphalan with a stem cell transplant. This combination aims to reset the immune system and potentially stop the disease progression. By using the patient’s own stem cells, the treatment also minimizes the risk of rejection and could lead to longer-lasting remission compared to current options.

What evidence suggests that this treatment might be an effective treatment for autoimmune neurological diseases?

In this trial, participants will receive a combination of specific drugs before a stem cell transplant to treat autoimmune neurological diseases. Anti-Thymocyte Globulin (ATG) helps reduce the immune system's attack on the nervous system and aids recovery. Carmustine effectively controls diseases like brain tumors. Etoposide, when combined with other treatments, improves outcomes for the nervous system. Melphalan is commonly used to prepare patients for stem cell transplants and has successfully treated other serious conditions. Together, these treatments aim to reset the immune system, offering hope to patients who haven't responded to other therapies. ^{6 7 8 9 10}

Who Is on the Research Team?

Leona Holmberg

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

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.

You haven't followed your doctor's instructions in the past.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11530368/

ATG and other serotherapy in conditioning regimens for ... Among responding centers, 11 (23.9%) perform HSCT for neurological AD indications, 7 (15.2%) for rheumatological ADs, 1 (2.2%) for hematological ...

2. nature.com nature.com/articles/s41409-025-02715-x

a retrospective analysis of the EBMT autoimmune diseases ... Overall, 2.0% of patients conditioned with BEAM/ATG and 1.0% with CYC/ATG died within 100 days from HSCT (p = 0.19). Overall, the incidence of ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/17698561/

Anti-thymocyte globulin (ATG) prevents autoimmune ... In both acute and relapsing remitting disease models, ATG treatment resulted in the attenuation from EAE, both in a preventive and early ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2352302617300297

Association between anti-thymocyte globulin exposure and ... One study investigating ATG exposures showed that low exposure after HCT led to improvements in immune reconstitution and overall survival. Results from most ...

5. diabetesjournals.org diabetesjournals.org/care/article/41/9/1917/40730/Low-Dose-Anti-Thymocyte-Globulin-ATG-Preserves

Low-Dose Anti-Thymocyte Globulin (ATG) Preserves β-Cell ... HbA1c was significantly reduced at 1 year in subjects treated with ATG and ATG/GCSF, P = 0.002 and 0.011, respectively. CONCLUSIONS. Low-dose ...

6. thymoglobulin.com thymoglobulin.com/efficacy-safety-data

Efficacy & Safety Read efficacy & safety data of Thymoglobulin compared to other immunosuppressants based on BPAR, graft loss, death, or lost to follow-up.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6767488/

Rabbit anti‐thymocyte globulin for the prevention of acute ... In a pooled analysis of data from the 1010 and TAXI trials, the reported incidence of treatment failure was 25.1% and 36% in the rATG and IL2RA treatment groups ...

8. go.drugbank.com go.drugbank.com/drugs/DB00098

Antithymocyte immunoglobulin (rabbit) Antithymocyte immunoglobulin (rabbit) is a purified form of rabbit anti-thymocyte antibodies used for immunosuppression in patients receiving kidney transplants ...

9. mayoclinic.org mayoclinic.org/drugs-supplements/antithymocyte-globulin-rabbit-intravenous-route/description/drg-20061948

Antithymocyte globulin rabbit (intravenous route) Anti-thymocyte globulin (rabbit) injection is used together with other medicines to prevent and treat the body from rejecting a transplanted kidney.

10. thymoglobulin.com thymoglobulin.com/

Thymoglobulin® [Anti-thymocyte Globulin (Rabbit)]: FDA ... Multiple Risk factors should be considered when evaluating the risk for acute rejection. · Thymoglobulin may induce immunosuppression through multiple pathways.