Optimal Conditioning Regimen for Autologous Transplantation of Relapsing Remitting Multiple Sclerosis

November 7, 2023 updated by: Scripps Health

Optimal Conditioning Regimen Protocol for Autologous Hematopoietic Stem Cell Transplantation of Relapsing Remitting Multiple Sclerosis

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Autologous hematopoietic stem cell transplantation (HSCT) in patients with active relapsing remitting multiple sclerosis (RRMS) halts disease progression, improves neurologic disability and quality of life, and provides a prolonged drug-free remission. A "position paper" by neurologists and hematologists under the American Society of Transplant and Cellular Therapy (ASTCT) has recommended autologous HSCT as standard of care, clinical evidence available, for treatment-refractory relapsing MS with high risk of future disability. Similarly, the EBMT has recommended the use of HSCT as "standard or care" for patients with highly active RRMS failing at least one DMT. Currently, the optimal conditioning regimen in terms of safety and efficacy is unknown. Herein, we will compare the two most commonly used regimens cyclophosphamide/ATG, or cyclophosphamide/rituximab in terms of safety and efficacy.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • California
      • La Jolla, California, United States, 92037
        • Scripps Green Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 58 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age 18-58 years old
  2. 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
  3. Since diagnosis a new MRI T2 lesion or since diagnosis a gadolinium positive lesion and at least one T2 weighted lesion

  4. RRMS with a history of:

    1. 2 or more "active flares" in the prior 12 months despite either copaxone or interferon; or
    2. 1 or more "active flares" in the prior year despite a 2nd or 3rd generation DMT; or
    3. 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

Exclusion Criteria:

  1. CIS- clinically isolated lesion
  2. isolated optic neuritis
  3. Primary progressive MS b) Nonactive SPSM (defined as no new or enhancing lesions in last 12 months)
  4. spasticity or clinical stiffness of leg(s) unless there is documented new MRI enhancement within the past 12 months.
  5. hyperreflexia or clonus
  6. other immune neurologic disease such as NMO, CIDP, Stiff person syndrome, myasthenia gravis
  7. genetic neurologic diseases such as CMT or spinal cerebellar degeneration
  8. 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)
  9. insulin dependent diabetes mellitus
  10. sickle cell disease
  11. thalassemia major
  12. porphyria
  13. a current or prior cancer / malignancy except for cutaneous basal cell carcinoma or carcinoma in situ (completely excised)

  14. Hepatic:

    1. Liver function test (AST or ALT) > 2 x upper limit of normal or
    2. bilirubin > 2.0 mg /dl

  15. Pulmonary:

    1. DLCO < 60% of normal or;
    2. Asthma not easily corrected with bronchodilator therapy or;
    3. Pulmonary artery hypertension (pulmonary artery systolic pressure (PASP) > 40 mmHg on echocardiogram or by cardiac catheterization a mean pulmonary artery pressure (mPAP) > 25 mmHg; a cardiac catheterization for pulmonary artery pressures is only performed if clinically indicated)

  16. Renal:

    1. creatinine > 2.0 mg/dl, or
    2. nephrotic syndrome

  17. Cardiac:

    1. Acute myocardial infarction (AMI) within the last year, and if history of AMI not being approved by cardiology as low risk or not at increased risk for another AMI: or
    2. Persistent arrythmia not controlled with medication;
    3. Any patient requiring medication for an arrhythmia must be pre-approved by cardiology, or
    4. left ventricular ejection fraction < 45%

  18. Hematology

    1. Hereditary coagulopathy or currently receiving anticoagulation therapy
    2. platelets < 100,000
    3. myelodysplastic syndrome

  19. Infection:

    1. HIV,
    2. hepatitis B
    3. hepatitis C
    4. positive quantiferon gold (tuberculosis test) (may start HSCt once seen by ID and started on anti-tuberculous therapy, that will be continued throughout transplant, if asymptomatic),

    d) active infection at time of hospital admission (except UTI)

  20. EDSS < 2.0 at time of enrollment or insurance submission
  21. Inability to comprehend or give or sign informed consent
  22. Pregnancy (positive serum or urine HCG test) or breast feeding
  23. Failure to comprehend infertility as a complication.
  24. Failure to offer sperm or oocyte collection and storage
  25. Before HSCT failure to be Free of alemtuzumab for 12 months
  26. Before HSCT failure to be Free of natalizumab for 5 months
  27. Before HSCT failure to be Free of rituximab or ocrelizumab for 5 months
  28. Before HSCT failure to be Free of fingolimod for 3 months
  29. Before HSCT failure to be Free of dimethyl fumarate (tecfidera) for 3 months
  30. Before HSCT failure of teriflunomide to have plasma levels < 0.02 mg/L after either oral cholestyramine or activated charcoal clearance.
  31. Prior mitoxantrone
  32. Prior cladribine

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: Cyclophosphamide/ATG Conditioning Regimen
Cyclophosphamide (200 mg /kg) / rabbit antithymocyte globulin (6.0 mg/kg)
Other: Autologous hematopoietic stem cell transplantation
Autologous hematopoietic stem cell transplantation
Drug: Cyclophosphamide/ATG
Cyclophosphamide/ATG
Other: Cyclophosphamide/Rituximab Conditioning Regimen
Cyclophosphamide (200 mg/kg) / rituximab (1000 mg).
Other: Autologous hematopoietic stem cell transplantation
Autologous hematopoietic stem cell transplantation
Drug: Cyclophosphamide/Rituximab
Cyclophosphamide/Rituximab

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Durability of remission between two arms
Time Frame: Time to first confirmed acute relapse or 5 years after treatment which ever comes first
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Neurologic Disability
Time Frame: From initiation of study to completion, up until 5 years after treatment
Defined by change in EDSS (Expanded Disability Status Scale, ranges from 0 to 10 with 0 normal and 10 worst)
From initiation of study to completion, up until 5 years after treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Scripps Health

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: David J Hermel, MD, Scripps Health

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 12, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 29, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 1, 2022

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 9, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 7, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB-21-7874

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings