Optimal Conditioning Regimen for Autologous Transplantation of Relapsing Remitting Multiple Sclerosis

NCT05482542 | Withdrawn DMC

• 1 other identifier: IRB-21-7874
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to compare two non-myeloablative conditioning regimens (combination of chemotherapy and immune specific proteins against immune cells) for relapsing remitting multiple sclerosis (RRMS). The two conditioning regimens are the most commonly used world wide in clinical practice for the treatment of multiple sclerosis (MS). The first investigational conditioning regimen is cyclophosphamide (chemotherapy) and rATG (rabbit anti-thymocyte globulin, a protein against immune cells). The second investigational conditioning regimen includes the same dose of cyclophosphamide (chemotherapy) and rituximab (a protein against immune cells). Both cyclophosphamide and either rATG or rituximab are given to kill immune cells that are thought to be causing MS, followed by return of one's own previously collected blood stem cells (autologous stem cell transplant) to hasten recovery. The goal of this study is to assess the difference of these treatments in terms of toxicity and efficacy.

Conditions

Multiple Sclerosis, Relapsing-Remitting

Keywords

Autologous Hematopoietic Stem Cell Transplant

Outcome Measures

Primary Outcomes (1)

• Durability of remission between two arms

  Defined as the time to first confirmed acute relapse or 5 years after treatment which ever comes first

  Time to first confirmed acute relapse or 5 years after treatment which ever comes first

Secondary Outcomes (1)

• Neurologic Disability

  From initiation of study to completion, up until 5 years after treatment

Study Arms (2)

Cyclophosphamide/ATG Conditioning Regimen

OTHER

Cyclophosphamide (200 mg /kg) / rabbit antithymocyte globulin (6.0 mg/kg)

Other: Autologous hematopoietic stem cell transplantation; Drug: Cyclophosphamide/ATG

Cyclophosphamide/Rituximab Conditioning Regimen

OTHER

Cyclophosphamide (200 mg/kg) / rituximab (1000 mg).

Other: Autologous hematopoietic stem cell transplantation; Drug: Cyclophosphamide/Rituximab

Interventions

Autologous hematopoietic stem cell transplantation OTHER

Autologous hematopoietic stem cell transplantation

Cyclophosphamide/ATG Conditioning Regimen; Cyclophosphamide/Rituximab Conditioning Regimen

Cyclophosphamide/ATG DRUG

Cyclophosphamide/ATG

Cyclophosphamide/ATG Conditioning Regimen

Cyclophosphamide/Rituximab DRUG

Cyclophosphamide/Rituximab

Cyclophosphamide/Rituximab Conditioning Regimen

Eligibility Criteria

• Age: 18 Years - 58 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-58 years old
• MRI T2 hyperintense lesions with at least 1 lesion in two or more of the following locations: periventricular, cortical or juxtacortical, infratentorial, or 1 spinal lesion
• Since diagnosis a new MRI T2 lesion or since diagnosis a gadolinium positive lesion and at least one T2 weighted lesion
• RRMS with a history of:
• or more "active flares" in the prior 12 months despite either copaxone or interferon; or
• or more "active flares" in the prior year despite a 2nd or 3rd generation DMT; or
• Active secondary progressive MS (aSPMS) with 2 or more gadolinium enhancing lesions with at least 1 gadolinium enhancing lesion \> 5 mm in longest dimension within the last 9 months

You may not qualify if:

• CIS- clinically isolated lesion
• isolated optic neuritis
• Primary progressive MS b) Nonactive SPSM (defined as no new or enhancing lesions in last 12 months)
• spasticity or clinical stiffness of leg(s) unless there is documented new MRI enhancement within the past 12 months.
• hyperreflexia or clonus
• other immune neurologic disease such as NMO, CIDP, Stiff person syndrome, myasthenia gravis
• genetic neurologic diseases such as CMT or spinal cerebellar degeneration
• another autoimmune diagnosis such as systemic lupus erythematosus, systemic sclerosis, Behcets, or crohn's disease, etc (with the exception of hypo or hyperthyroidism or history of ITP or AIHA that is in remission)
• insulin dependent diabetes mellitus
• sickle cell disease
• thalassemia major
• porphyria
• a current or prior cancer / malignancy except for cutaneous basal cell carcinoma or carcinoma in situ (completely excised)
• Hepatic:
• Liver function test (AST or ALT) \> 2 x upper limit of normal or

Sponsors & Collaborators

• Scripps Health: lead

Study Sites (1)

Scripps Green Hospital

La Jolla, California, 92037, United States

Location

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting

Interventions

Cyclophosphamide; Rituximab

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• David J Hermel, MD

  Scripps Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2022
• First Posted: August 1, 2022
• Study Start: January 1, 2023
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: November 9, 2023

Record last verified: 2022-12

Locations

US (1)