What is the mechanism of action of this treatment?

Common treatments for Multiple Sclerosis (MS) include immunosuppressive therapies and disease-modifying therapies (DMTs). High-dose chemotherapy and antithymocyte globulin, used before autologous stem cell transplant, work by significantly suppressing the immune system to halt its attack on the nervous system. This is followed by the infusion of the patient's own stem cells to aid in bone marrow recovery and restore normal immune function. These mechanisms are crucial for MS patients as they aim to reset the immune system, reduce disease activity, and potentially improve long-term outcomes by preventing further neurological damage.

What side effects are associated with this type of intervention?

Common treatments for Multiple Sclerosis that involve immune system suppression and bone marrow recovery include high-dose chemotherapy and autologous stem cell transplantation (HSCT). High-dose chemotherapy can lead to side effects such as severe myelosuppression, increased risk of infections, and organ toxicity. HSCT, while potentially beneficial, carries risks including transplant-related complications, infections, and in some cases, mortality. Other immunosuppressive treatments like cyclophosphamide and antithymocyte globulin can cause adverse effects such as bone marrow suppression, increased susceptibility to infections, and potential organ damage.

What prior FDA approvals exist?

FDA-approved treatments for Multiple Sclerosis (MS) that involve immune system suppression and bone marrow recovery include high-dose chemotherapy regimens and autologous stem cell transplants. These treatments aim to reset the immune system by using high-dose chemotherapy agents such as carmustine, etoposide, cytarabine, and melphalan, often combined with antithymocyte globulin (ATG) to suppress the immune system before the transplant. This approach helps to stop the immune system from attacking the nervous system and allows for the recovery of bone marrow function through the infusion of the patient's own stem cells.

What other types of research exist?

Promising novel alternatives to high-dose chemotherapy and antithymocyte globulin before autologous stem cell transplant for multiple sclerosis patients include: 1) Hematopoietic Stem Cell Transplantation (HSCT) with less intensive conditioning regimens, which aim to reduce toxicity while maintaining efficacy. 2) Immunoablation followed by autologous HSCT, which has shown high rates of event-free survival and improvements in neurologic function. 3) Emerging biologic therapies and monoclonal antibodies that target specific immune pathways involved in MS, potentially offering more targeted and less toxic options for immune system modulation.

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Immunosuppressant

Stem Cell Transplant for Autoimmune Neurological Diseases

Phase 2

Waitlist Available

Led By Leona Holmberg

Research Sponsored by Fred Hutchinson Cancer Research Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients with an autoimmune disorder of the central or peripheral nervous system will be eligible; this will include: Primary Central Nervous System (CNS) vasculitis, Rasmussen's encephalitis, Autoimmune peripheral neuropathy (anti-Hu [Anna-1], anti-GM1 [GD1b], anti-MAG, anti-ganglioside, anti-sulfatide), Autoimmune cerebellar degeneration, Gait Ataxia with Late age Onset Polyneuropathy (GALOP), Stiff Person Syndrome, Chronic Inflammatory Demyelinating Polyneuropathy, Myasthenia Gravis, Lambert-Eaton myasthenic syndrome, Human T-cell lymphotropic virus (HTLV)-1-associated myelopathy (HAM) / tropical spastic paraparesis (TSP), Opsoclonus/myoclonus (anti-Ri), Neuromyelitis optica, Multiple sclerosis, Other central or peripheral nervous system autoimmune diseases as approved by study neurologists and the Fred Hutchinson Cancer Research Center (FHCRC) faculty at Patient Care Conference (PCC)

Patients must satisfy the criteria for a diagnosis of one of the severe neurological autoimmune disorders outlined

Must not have

Age >= 71 years

Patients with pulmonary, cardiac, hepatic or renal impairment that would limit their ability to receive cytoreductive therapy and compromise their survival

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects include weakened immune system leading to increased infection risk; blood count fluctuations; organ inflammation from the drugs used; and complications from the stem cell transplant process.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have an autoimmune disorder affecting my nervous system.

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I have been diagnosed with a severe neurological autoimmune disorder.

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I have tried at least 2 standard treatments for my condition without success.

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I have an autoimmune disorder affecting my nervous system.

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I have inflammation of blood vessels in my brain.

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I have been diagnosed with Rasmussen's encephalitis.

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I have been diagnosed with GALOP.

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I have been diagnosed with Chronic Inflammatory Demyelinating Polyneuropathy.

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I have been diagnosed with a severe neurological autoimmune disorder.

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I have been diagnosed with a severe neurological autoimmune disorder.

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I am 70 years old or younger.

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My scans show active disease or my condition is getting worse.

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I have tried at least 2 standard treatments for my condition without success.

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I am the identical twin of a patient in this study, proven by blood and genetic tests.

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I am willing to undergo several apheresis procedures or bone marrow harvests if I'm under 12.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am 71 years old or older.

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I have lung, heart, liver, or kidney problems that could affect my treatment.

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

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I have been diagnosed with myelodysplasia.

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I have an active cancer other than skin cancer.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Incidence of grades 4-5 regimen-related toxicity

Secondary study objectives

Disease responses

Engraftment kinetics

Number of subjects achieving greater than or equal to 4.0 x 10^6 CD34+ cells/kg, after up to two peripheral blood stem cell mobilizations

+2 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (immunosuppressive therapy followed by transplant)Experimental Treatment10 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cytarabine

2016

Completed Phase 3

~3330

Etoposide

2010

Completed Phase 3

~2960

Prednisone

2014

Completed Phase 4

~2500

Anti-Thymocyte Globulin

2009

Completed Phase 4

~1040

Autologous Hematopoietic Stem Cell Transplantation

2017

Completed Phase 3

~2090

Carmustine

1990

Completed Phase 3

~1820

Peripheral Blood Stem Cell Transplantation

1997

Completed Phase 3

~1330

Melphalan

2008

Completed Phase 3

~1500

Syngeneic Bone Marrow Transplantation

2008

Completed Phase 2

~40

0 / 20Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Multiple Sclerosis (MS) include immunosuppressive therapies and disease-modifying therapies (DMTs). High-dose chemotherapy and antithymocyte globulin, used before autologous stem cell transplant, work by significantly suppressing the immune system to halt its attack on the nervous system. This is followed by the infusion of the patient's own stem cells to aid in bone marrow recovery and restore normal immune function. These mechanisms are crucial for MS patients as they aim to reset the immune system, reduce disease activity, and potentially improve long-term outcomes by preventing further neurological damage.