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High Dose Chemo With Stem Cell Transplant as Treatment for Multiple Sclerosis That Failed Prior Treatment

Primary Purpose

Multiple Sclerosis

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Alemtuzumab

Fludarabine

Cyclophosphamide

About this trial

This is an interventional treatment trial for Multiple Sclerosis

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age between 18-60, inclusive

Patients carry a diagnosis of multiple sclerosis, according to the McDonald's criteria for diagnosis (Polman et al, 2011).

Must have a neurologist providing the primary care for the MS and be willing to be evaluated for the multiple sclerosis by the two neurologists who are the co-investigators in the protocol.

Must be documented to be HIV negative.

An EDSS of 3.5 - 5.5

Patients must be able to give written consent.

Inflammatory disease despite primary disease modifying therapy with at least 6 months of interferon and another disease modifying therapy, including fingolimod,glativamir, natalizumab, and mitoxantrone. Failure is defined as two or more clinical relapses with documented neurologic changes (excluding sensory changes) within the year prior to the study. (NOTE: Relapses must have required treatment with corticosteroids). Failure may also be defined as one relapse (excluding sensory changes) treated with methylprednisone and, on a separate occasion within the previous 12 months, evidence of active inflammation (i.e. gadolinium enhancement on MRI scan of the CNS).

No previous history of allergic reaction to cyclophosphamide, G-CSF or mesna

Patients must not be pregnant

Failure to accept or comprehend irreversible sterility as a potential side effect of therapy.

Life expectancy of more than 6 months

No evidence of myelodysplastic syndrome on peripheral blood smear

Not allergic to cyclophosphamide, mesna, fludarabine or alemtuzumab

Baseline serum creatinine must be <1.5 mg/dL, left ventricular ejection fraction >55%, adequate pulmonary functions (oxygen saturation at room air of >90%), and AST and ALT not > 2x upper limits of normal, and no history of previous or active malignancy, except for localized cutaneous basal or squamous cell carcinoma in situ of the cervix.

Exclusion Criteria:

Diagnosis of primary progressive MS.

Sites / Locations

Amarillo Diagnostic Clinic
Dr Ruby Saulog
Texas Oncology

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Single Arm

Arm Description

Conditioning regimens with Alemtuzumab, Fludarabine, and Cyclophosphamide will be used for all patients.

Outcomes

Primary Outcome Measures

To evaluate the toxicity of autologous HPC transplant in patients with multiple sclerosis that have failed at least two lines of disease modifier therapy

All follow-up appointments will be carried out at Texas Oncology-Amarillo Cancer Center. Patients will be monitored for clinical toxicities and using laboratory blood tests for renal functions, hepatic functions, and bone marrow functions at At discharge post-transplant, then again at 6 weeks, 3 months, 6 months, 9 months, 12 months and after that 6 monthly until death..

Secondary Outcome Measures

To evaluate the effectiveness of high dose chemotherapy with HPC transplant for multiple sclerosis sclerosis that has failed at least two lines of therapy

hen rechecked Neurologic evaluations will be carried out in the offices of the two neurology co-Investigators and the information provided to the transplant physicians for record. Patient will also undergo a repeat MRI scan at 3 months, 6 months, 9 months, 12 months, and then after every 12 months until death, after the transplant to evaluate changes in the number of MS plaques. Subsequent MRI scan will be determined by the patient's neurologist as is needed clinically.

Full Information

NCT ID

NCT01679041

First Posted

August 29, 2012

Last Updated

November 21, 2013

Sponsor

Seah Lim M.D.

1. Study Identification

Unique Protocol Identification Number

NCT01679041

Brief Title

High Dose Chemo With Stem Cell Transplant as Treatment for Multiple Sclerosis That Failed Prior Treatment

Official Title

A Phase II Study of High Dose Chemotherapy With Autologous Hematopoietic Progenitor Cell Transplant for Multiple Sclerosis That Failed at Least Two Lines of Therapy

Study Type

Interventional

2. Study Status

Record Verification Date

November 2013

Overall Recruitment Status

Terminated

Why Stopped

Insufficient accruals; PI leaving site

Study Start Date

November 2012 (undefined)

Primary Completion Date

November 2013 (Actual)

Study Completion Date

November 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Seah Lim M.D.

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this study is to evaluate the toxicity and the effectiveness of high dose chemotherapy with HPC transplant Multiple Sclerosis that has failed at least two lines of therapy

Detailed Description

Multiple sclerosis is an inflammatory autoimmune disease characterized by loss of myelin and axonal damage, having typical contrast-enhanced MRI foci as an imaging counterpart. MS shows three main patterns of clinical course: relapsing/remitting, primary progressive and secondary progressive.Concerning disease pattern, secondary progressive is the standard indication, to avoid overtreatment in relapsing/remitting patients or ineffectual treatment in primary relapsing patients. Currently, MS is the most common autoimmune disease that have been treated with autologous HPC transplants (Fagius et al, 2009; Burt et al, 2009; Saccardi et al, 2006). More than 350 consecutive cases have been reported by the EBMT over the last decade. Most patients who underwent autologous HPC transplant for MS in the early studies had secondary progressive MS, and relatively fewer had relapsing remitting disease, with a Kurtzke Expanded Disability Status Scale (EDSS) of 3.0-9.5 at the time of transplant. Significant objective and subjective improvements have been reported in up to 70% of these patients. The following conditioning regimens will be used, with Alemtuzumab, Fludarabine, and Cyclophosphamide will be used for all patients. Prophylaxis of Acyclovir, Levaquin, and Fluconazole will be given to prevent infections. The autologous HPC will be infused within 48-72 hours of completing the chemotherapy. The patients will receive additional supportive care medications and treatments as necessary. Neutrophil engraftment will be defined as the day on which the ANC rises to > 500 cells/ml for two consecutive days. Platelet engraftment will be defined as the first day on which the platelet count rises to > 20,000/ml over a 7-day interval without transfusion support.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Sclerosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

1 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Single Arm

Arm Type

Experimental

Arm Description

Conditioning regimens with Alemtuzumab, Fludarabine, and Cyclophosphamide will be used for all patients.

Intervention Type

Drug

Intervention Name(s)

Alemtuzumab

Intervention Description

Alemtuzumab 10 mg given IV on day 1 of the 5 day conditional regimen

Intervention Type

Drug

Intervention Name(s)

Fludarabine

Intervention Description

Fludarabine 25mg/m2 daily given IV on days 1-5 of the 5 day conditioning regimen

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Intervention Description

Cyclophosphamide is given 3 gm/m2 for mobilization, and then repeated during 5 day conditioning regimen w/ doses of 50mg/kg/day on days 1-4

Primary Outcome Measure Information:

Title

To evaluate the toxicity of autologous HPC transplant in patients with multiple sclerosis that have failed at least two lines of disease modifier therapy

Description

Time Frame

At 5 years post transplant

Secondary Outcome Measure Information:

Title

To evaluate the effectiveness of high dose chemotherapy with HPC transplant for multiple sclerosis sclerosis that has failed at least two lines of therapy

Description

Time Frame

Assessed at baseline, tat 3 months, 6 months, 9 months, 12 months, and then after every 12 months until death

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age between 18-60, inclusive Patients carry a diagnosis of multiple sclerosis, according to the McDonald's criteria for diagnosis (Polman et al, 2011). Must have a neurologist providing the primary care for the MS and be willing to be evaluated for the multiple sclerosis by the two neurologists who are the co-investigators in the protocol. Must be documented to be HIV negative. An EDSS of 3.5 - 5.5 Patients must be able to give written consent. Inflammatory disease despite primary disease modifying therapy with at least 6 months of interferon and another disease modifying therapy, including fingolimod,glativamir, natalizumab, and mitoxantrone. Failure is defined as two or more clinical relapses with documented neurologic changes (excluding sensory changes) within the year prior to the study. (NOTE: Relapses must have required treatment with corticosteroids). Failure may also be defined as one relapse (excluding sensory changes) treated with methylprednisone and, on a separate occasion within the previous 12 months, evidence of active inflammation (i.e. gadolinium enhancement on MRI scan of the CNS). No previous history of allergic reaction to cyclophosphamide, G-CSF or mesna Patients must not be pregnant Failure to accept or comprehend irreversible sterility as a potential side effect of therapy. Life expectancy of more than 6 months No evidence of myelodysplastic syndrome on peripheral blood smear Not allergic to cyclophosphamide, mesna, fludarabine or alemtuzumab Baseline serum creatinine must be <1.5 mg/dL, left ventricular ejection fraction >55%, adequate pulmonary functions (oxygen saturation at room air of >90%), and AST and ALT not > 2x upper limits of normal, and no history of previous or active malignancy, except for localized cutaneous basal or squamous cell carcinoma in situ of the cervix. Exclusion Criteria: Diagnosis of primary progressive MS.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Seah Lim, MD

Organizational Affiliation

Texas Oncology

Official's Role

Principal Investigator

Facility Information:

Facility Name

Amarillo Diagnostic Clinic

City

Amarillo

State/Province

Texas

ZIP/Postal Code

79106

Country

United States

Facility Name

Dr Ruby Saulog

City

Amarillo

State/Province

Texas

ZIP/Postal Code

79106

Country

United States

Facility Name

Texas Oncology

City

Amarillo

State/Province

Texas

ZIP/Postal Code

79106

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

19186105

Citation

Burt RK, Loh Y, Cohen B, Stefoski D, Balabanov R, Katsamakis G, Oyama Y, Russell EJ, Stern J, Muraro P, Rose J, Testori A, Bucha J, Jovanovic B, Milanetti F, Storek J, Voltarelli JC, Burns WH. Autologous non-myeloablative haemopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: a phase I/II study. Lancet Neurol. 2009 Mar;8(3):244-53. doi: 10.1016/S1474-4422(09)70017-1. Epub 2009 Jan 29. Erratum In: Lancet Neurol. 2009 Apr;8(4):309. Stefosky, Dusan [corrected to Stefoski, Dusan].

Results Reference

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PubMed Identifier

17133541

Citation

Burt RK, Marmont A, Oyama Y, Slavin S, Arnold R, Hiepe F, Fassas A, Snowden J, Schuening F, Myint H, Patel DD, Collier D, Heslop H, Krance R, Statkute L, Verda L, Traynor A, Kozak T, Hintzen RQ, Rose JW, Voltarelli J, Loh Y, Territo M, Cohen BA, Craig RM, Varga J, Barr WG. Randomized controlled trials of autologous hematopoietic stem cell transplantation for autoimmune diseases: the evolution from myeloablative to lymphoablative transplant regimens. Arthritis Rheum. 2006 Dec;54(12):3750-60. doi: 10.1002/art.22256. No abstract available.

Results Reference

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PubMed Identifier

18805841

Citation

Fagius J, Lundgren J, Oberg G. Early highly aggressive MS successfully treated by hematopoietic stem cell transplantation. Mult Scler. 2009 Feb;15(2):229-37. doi: 10.1177/1352458508096875. Epub 2008 Sep 19.

Results Reference

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PubMed Identifier

17942513

Citation

Kimiskidis V, Sakellari I, Tsimourtou V, Kapina V, Papagiannopoulos S, Kazis D, Vlaikidis N, Anagnostopoulos A, Fassas A. Autologous stem-cell transplantation in malignant multiple sclerosis: a case with a favorable long-term outcome. Mult Scler. 2008 Mar;14(2):278-83. doi: 10.1177/1352458507082604. Epub 2007 Oct 17.

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PubMed Identifier

9040585

Citation

Lim SH, Kell J, al-Sabah A, Bashi W, Bailey-Wood R. Peripheral blood stem-cell transplantation for refractory autoimmune thrombocytopenic purpura. Lancet. 1997 Feb 15;349(9050):475. doi: 10.1016/S0140-6736(05)61187-7. No abstract available.

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PubMed Identifier

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Citation

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PubMed Identifier

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Citation

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PubMed Identifier

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Citation

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PubMed Identifier

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Citation

Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L, Lublin FD, Montalban X, O'Connor P, Sandberg-Wollheim M, Thompson AJ, Waubant E, Weinshenker B, Wolinsky JS. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011 Feb;69(2):292-302. doi: 10.1002/ana.22366.

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PubMed Identifier

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Citation

Saccardi R, Di Gioia M, Bosi A. Haematopoietic stem cell transplantation for autoimmune disorders. Curr Opin Hematol. 2008 Nov;15(6):594-600. doi: 10.1097/MOH.0b013e3283136700.

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PubMed Identifier

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Citation

Saccardi R, Kozak T, Bocelli-Tyndall C, Fassas A, Kazis A, Havrdova E, Carreras E, Saiz A, Lowenberg B, te Boekhorst PA, Gualandio F, Openshaw H, Longo G, Pagliai F, Massacesi L, Deconink E, Ouyang J, Nagore FJ, Besalduch J, Lisukov IA, Bonini A, Merelli E, Slavino S, Gratwohl A, Passweg J, Tyndall A, Steck AJ, Andolina M, Capobianco M, Martin JL, Lugaresi A, Meucci G, Saez RA, Clark RE, Fernandez MN, Fouillard L, Herstenstein B, Koza V, Cocco E, Baurmann H, Mancardi GL; Autoimmune Diseases Working Party of EBMT. Autologous stem cell transplantation for progressive multiple sclerosis: update of the European Group for Blood and Marrow Transplantation autoimmune diseases working party database. Mult Scler. 2006 Dec;12(6):814-23. doi: 10.1177/1352458506071301.

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High Dose Chemo With Stem Cell Transplant as Treatment for Multiple Sclerosis That Failed Prior Treatment

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