Table 1.
Phase II Studies in Autologous HCT for MS
| Phase II Single Arm | Phase II Randomized | |||
|---|---|---|---|---|
| Study and/or Sponsor |
HALT MS ITN033AI |
MS BMT Canada |
ASTIMS EBMT |
Northwestern University |
| Transplant Arm | ||||
| Mobilization | GCSF + prednisone | Cy + GCSF | Cy + GCSF | Cy + GCSF |
| Graft | CD34 selected | CD34 selected | Unmanipulated | Unmanipulated |
| Conditioning | BEAM + ATG | Busulfan + Cy | BEAM + ATG | Cy + ATG |
| Alternative Arm | ||||
| NA | NA | Mitoxantrone | FDA-approved standard of care | |
| Inclusion / Exclusion | ||||
| Target MS Population | Relapsing remitting or progressive relapsing MS | Active MS with relapses or progression | Relapsing remitting or progressive relapsing or secondary progressive MS | Inflammatory MS failing interferon therapy |
| Age | 18–60 | 18–50 | 18–50 | 18–55 |
| EDSS | 3.0–5.5 | 3.0–6.0 | 3.5–6.5 | 2.0–6.0 |
| MS Criteria | Duration <15 years from diagnosis; T2 abnormalities on brain MRI consistent with MS; ≥ 2 relapses in <18 mo; worsening of EDSS; failure of standard drug therapy | MRI findings meet criteria of MS; evidence of current disease activity including worsening of EDSS in last 18 months or 2 relapses in last year or 3 relapses in last 3 years; failed at least one immunosuppressive drug | Relapsing remitting MS with at least 2 relapses per year and enhancing lesions on MRI; relapsing progressive MS with worsening EDSS during last year and enhancing lesions on MRI; secondary progressive MS with worsening EDSS during last year and enhancing lesions on MRI unless rapid deterioration | Inflammatory disease, based on both clinical and MRI activity, after ≥ 6 months of interferon or copaxone |
| Study Design | ||||
| Primary Outcome | Progression free survival at 5 years | Progression free survival at 3 years | New T2 lesions per year | Progression free survival at 5 years |
| Primary Outcome Measure | EDSS and/or clinical relapse and/or new MRI abnormalities consistent with MS | EDSS | MRI imaging (EDSS is a secondary outcome measure) | EDSS |
| Projected Accrual | 25 | 24 | 30 (21 accrued) | 110 |
| Date of Activation | July 2006; enrollment complete September 2009 | August 2001; enrollment complete July 2009 | January 2005; closed November 2009 due to lack of accrual | January 2006; number enrolled not available |
| References | ClinicalTrials.gov NCT00288626 http://www.halt-ms.org | Atkins A, Freedman M (2009);39 Chen JT et al (2006)40 | http://www.astims.org Mancardi G, Saccardi R (2008)4 | ClinicalTrials.gov NCT00273364 |