Allogeneic Hematopoietic Cell Transplantation After Nonmyeloablative Conditioning for Patients With Severe Systemic Sclerosis
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00622895|
Recruitment Status : Recruiting
First Posted : February 25, 2008
Last Update Posted : March 8, 2017
The purpose of the study is to examine the safety and effectiveness of a reduced intensity conditioning regimen and allogeneic bone marrow transplant for people with systemic sclerosis. In an allogeneic bone marrow transplant procedure, bone marrow is taken from a healthy donor and transplanted into the patient. Bone marrow can be donated by a family member or an unrelated donor who is a complete tissue type match.
Participants will receive the chemotherapy and low dose radiation conditioning regimen consisting of the following: Fludarabine will be given intravenously for 5 days. Cyclophosphamide will be given intravenously on the first and second day. After completing the fludarabine and cyclophosphamide, patients will receive a single low dose of total body irradiation. The next day, patients will receive the allogeneic bone marrow transplant. On the third and fourth day after the transplant, patients will receive high dose intravenous cyclophosphamide. This is given to help prevent two complications: (1) graft rejection, which occurs when the body's immune system rejects the donor bone marrow, and (2) graft-versus-host disease (GVHD), which is when the donor immune cells attack the patient's normal tissues. On the fifth day after the transplant, patients will start receiving two additional medications: tacrolimus and mycophenolic acid (MPA, Myfortic), to help prevent GVHD. Patients will receive mycophenolic acid for about 5 weeks and tacrolimus for about 6 months. Also beginning on the fifth day after the transplant, patients will receive daily injections of a growth factor called granulocyte-colony stimulating factor (G-CSF), which is a protein that increases the white blood cell count; G-CSF will be continued until the patient's white blood cell count has returned to normal levels.
Patients will remain closely monitored either in the outpatient clinic setting or in the hospital for approximately 2-3 months after the transplant, but possibly longer if there are complications. Follow-up study visits will occur at 6 months and then at 1, 2, 3, 4, and 5 years after the transplant. Study researchers will keep track of the patient's medical condition after leaving the transplant center by phone calls or mailings to patients and their doctors once a year for the rest of the study participants' lives.
|Condition or disease||Intervention/treatment||Phase|
|Systemic Scleroderma Severe Systemic Sclerosis||Drug: fludarabine phosphate Drug: Mycophenolic Acid Drug: tacrolimus Radiation: total-body irradiation Procedure: bone marrow transplantation Procedure: reduced intensity allogeneic hematopoietic stem cell transplantation Procedure: quality-of-life assessment Other: laboratory biomarker analysis Other: flow cytometry Procedure: biopsy Drug: cyclophosphamide||Phase 1 Phase 2|
I. To determine the safety and potential efficacy of reduced intensity conditioning with fludarabine/cyclophosphamide/low-dose total body irradiation (TBI) and allogeneic hematopoietic cell transplantation (HCT) for the stabilization or regression of disease manifestations of severe systemic sclerosis (SSc).
I. To determine whether stable allogeneic donor engraftment can be safely established with reduced intensity conditioning followed by matched sibling or unrelated donor bone marrow transplantation in patients with severe SSc.
Patients receive fludarabine phosphate intravenously (IV) on days -6, -5, -4, -3 and -2 and Cyclophosphamide IV on days -6, -5, and undergo 2 Gray TBI on day -1. Patients receive human leukocyte antigen (HLA)-matched donor bone marrow transplantation on day 0. Patients then receive cyclophosphamide IV on days +3 and +4, and beginning day +5 they start tacrolimus orally (PO) and enteric coated mycophenolic acid.
After completion of initial study treatment, patients are followed up at 6 months and then annually for 5 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Allogeneic Hematopoietic Cell Transplantation After Nonmyeloablative Conditioning for Patients With Severe Systemic Sclerosis|
|Study Start Date :||September 2006|
|Estimated Primary Completion Date :||March 2018|
Experimental: Treatment: allogeneic HCT after reduced intensity conditioning
Patients receive fludarabine phosphate IV on days -4, -3 and -2, cyclophosphamide IV over 1-2 hours on days -6, -5, 3, and 4, and undergo low-dose TBI on day -1. Patients receive bone marrow transplantation on day 0. Patients then receive cyclophosphamide IV on days +3 and +4, and beginning day +5 they start tacrolimus orally (PO) and mycophenolic acid.
Drug: fludarabine phosphate
Other Names:Drug: Mycophenolic Acid
Other Name: MyforticDrug: tacrolimus
Other Names:Radiation: total-body irradiation
Other Name: TBIProcedure: bone marrow transplantation
Other Names:Procedure: reduced intensity allogeneic hematopoietic stem cell transplantation
Undergo transplantationProcedure: quality-of-life assessment
Other Name: quality of life assessmentOther: laboratory biomarker analysis
Correlative studiesOther: flow cytometry
Correlative studiesProcedure: biopsy
Punch biopsy of skin involved with scleroderma
Other Name: biopsiesDrug: cyclophosphamide
- Event-free survival (EFS) [ Time Frame: 2 years ]The events will be defined as any one of the following: death; respiratory failure; renal failure, as defined by chronic dialysis > or = 6 months or kidney transplantation; occurrence of cardiomyopathy, confirmed by clinical CHF (New York Class III or IV) or LVEF < 30% by echocardiogram, sustained for at least 3 months despite therapy; organ dysfunction specific events must be documented on at least two occasions > or = 3 months apart, or sustained for a 3-month period (documented from the first occurrence).
- EFS [ Time Frame: 5 years ]
- Overall survival [ Time Frame: Up to 5 years ]Event is defined as death due to any cause.
- Treatment-related mortality [ Time Frame: From time of transplant to 5 years ]Defined as death occurring at any time after start of allogeneic HCT and definitely or probably resulting from treatment given in the study and not associated with disease progression.
- Regimen-related toxicity (greater than or equal to Grade III) as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 [ Time Frame: Up to 5 years ]
- Incidence of definite and probable viral, fungal, and bacterial infections in each patient [ Time Frame: Up to 5 years ]
- Quality of life as assessed by the Modified Scleroderma Health Assessment Questionnaire (SHAQ) [ Time Frame: Up to 5 years ]The questionnaire includes eight general activity domains, derived from the Health Assessment Questionnaire Disability Index (HAQDI): dressing, arising, eating, walking, hygiene, reach, grip, and common daily activities; and 5 overall disease specific domains that include: Raynaud's phenomenon, finger ulcers, breathing, and intestinal problems. Each domain is composed of questions with visual analog scales from 0 to 100. Higher scores represent more disability.
- Quality of life as assessed by the Medical Outcome Short Form (36) Health Survey instrument (SF-36) [ Time Frame: Up to 5 years ]The Medical Outcome Short Form (36) Health Survey instrument (SF-36) is a general assessment of health quality of life with eight components: physical functioning, role limitations due to physical health, pain index, general health perceptions, vitality, social functioning, role limitations due to emotional problems and Mental Health Index. Each domain is positively scored, indicating that higher scores are associated with positive outcome.
- Skin score and pulmonary function tests [ Time Frame: Up to 5 years post-transplant ]
- Incidence of graft rejection [ Time Frame: Up to day +56 ]Engraftment is defined as achieving > 5% donor peripheral blood T cell chimerism by Day 56 after HCT. Primary graft failure is defined as a donor peripheral blood T cell chimerism peak of < 5% by Day 56 post-HCT. Methodological requirements for chimerism are as defined by institutional standard of practice. Secondary Graft Failure is defined as documented engraftment followed by loss of the graft with donor peripheral blood T cell chimerism < 5% as demonstrated by a chimerism assay
- Incidence and severity of graft-versus-host disease (GVHD) [ Time Frame: Up to 5 years post-transplant ]The grading of acute and chronic GVHD will follow previously published guidelines and according to institutional standard of practice but will also include capture of symptoms and characterization of alternative causes. The highest level of organ abnormalities, the etiologies contributing to the abnormalities and biopsy results pertaining to GVHD will be identified. Since both GVHD and SSc involve the skin and the gastrointestinal tract, all diagnostic biopsies of these organs will be centrally reviewed by a study pathologist.
- Incidence of disease-modifying antirheumatic drugs (DMARDs) initiated post transplant to modify disease [ Time Frame: Up to 5 years post-transplant ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00622895
|United States, Colorado|
|Colorado Blood Cancer Institute||Recruiting|
|Denver, Colorado, United States, 80218|
|Contact: Richard A. Nash 720-754-4800 Richard.Nash@HealthONECares.com|
|Principal Investigator: Richard A. Nash|
|United States, Washington|
|Fred Hutch/University of Washington Cancer Consortium||Recruiting|
|Seattle, Washington, United States, 98109|
|Contact: George E. Georges 206-667-6886 email@example.com|
|Principal Investigator: George E. Georges|
|Principal Investigator:||George Georges||Fred Hutch/University of Washington Cancer Consortium|