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Nonmyeloablative Conditioning and Transplantation for Patients With Refractory Systemic Lupus Erythematosus (SLE)

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ClinicalTrials.gov Identifier: NCT02080195
Recruitment Status : Terminated (Study was unable to accrue subjects)
First Posted : March 6, 2014
Results First Posted : October 2, 2018
Last Update Posted : October 2, 2019
Sponsor:
Collaborator:
Maryland Stem Cell Research Fund
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Tracking Information
First Submitted Date  ICMJE February 28, 2014
First Posted Date  ICMJE March 6, 2014
Results First Submitted Date  ICMJE September 6, 2018
Results First Posted Date  ICMJE October 2, 2018
Last Update Posted Date October 2, 2019
Actual Study Start Date  ICMJE September 13, 2016
Actual Primary Completion Date March 28, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 6, 2018)
The Feasibility of the Conditioning Regimen and Post Transplantation Cyclophosphamide in Refractory SLE Patients With Donors Having Various Degrees of Matching [ Time Frame: 1 year ]
Number of participants who were alive at 1 year after transplant and who had not suffered graft rejection, acute or chronic GVHD, or Grade 3 or higher (CTCAE V4.0) adverse events.
Original Primary Outcome Measures  ICMJE
 (submitted: March 4, 2014)
The Feasibility of the Conditioning Regimen and Post Transplantation Cyclophosphamide in Refractory SLE Patients With Donors Having Various Degrees of Matching [ Time Frame: 60 days ]
Change History Complete list of historical versions of study NCT02080195 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 19, 2019)
  • RIFLE Score [ Time Frame: 1 year ]
    Change in Responder Index for Systemic Lupus Erythematosis (RIFLE) assessment. This is a qualitative assessment of organ function. The 12 month response will be assessed as: complete= complete or partial resolution in more than one organ, partial= complete or partial resolution in at least one organ, the same= no change or no worsening in any organ, worse= worsening in any organ
  • Survival [ Time Frame: 1 year ]
    Number of patients alive and alive without relapse, respectively.
  • Graft Failure [ Time Frame: 60 days ]
    Number of participants with primary and/or secondary graft failure.
  • Acute Graft Versus Host Disease (GVHD) [ Time Frame: Up to 2 years ]
    Percentage of participants who developed grades II-IV and grades III-IV acute GVHD. Acute GVHD is defined by the Przepiorka criteria, which stages the degree of organ involvement in the skin, liver, and gastrointestinal (GI) tract, based on severity, with Stage 1+ being least severe and stage 4+ being the most severe. Grading of acute GVHD is as follows: Grade I (skin involvement stages 1+ to 2+, with no liver or GI involvement), Grade II (skin involvement stages 1+ to 3+, liver 1+, GI tract 1+), Grade III (skin involvement stages 2+ to 3+, liver 1+, GI tract 2+ to 4+), Grade IV (skin involvement stages 4+, Liver 4+).
  • Chronic Graft Versus Host Disease (GVHD) [ Time Frame: Up to 2 years ]
    Percentage of participants who developed chronic GVHD as defined by the NIH consensus criteria. This system gives scores from 0 to 3 for Karnofsky performance score, skin, mouth, eyes, gastrointestinal, liver, lungs, joints, and genitals, as well as an overall severity (mild, moderate, or severe). Mild chronic GVHD involves only 1 or 2 organs or sites (except the lung), with no clinically significant functional impairment (maximum of score 1 in all affected organs or sites). Moderate chronic GVHD involves 1) at least 1 organ or site with clinically significant but no major disability (maximum score of 2 in any affected organ or site) OR 2) 3 or more organs or sites with no clinically significant functional impairment (maximum score of 1 in all affected organs or sites). Severe chronic GVHD indicates major disability caused by chronic GVHD (score of 3 in any organ or site).
Original Secondary Outcome Measures  ICMJE
 (submitted: March 4, 2014)
  • Evaluation of the improvement in the RIFLE score with the goal as target organ complete response with no worsening in any other organ [ Time Frame: 1 year ]
  • The overall survival (OS) and event-free survival (EFS) [ Time Frame: 1 year ]
  • The incidences of primary and secondary graft failure [ Time Frame: 60 days ]
  • The cumulative incidence of acute and chronic graft versus-host disease (GVHD) [ Time Frame: 100 days to 2 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Nonmyeloablative Conditioning and Transplantation for Patients With Refractory Systemic Lupus Erythematosus (SLE)
Official Title  ICMJE A Phase I/II Study of Nonmyeloablative Conditioning and Transplantation of Human Leukocyte Antigen (HLA)-Matched, Partially HLA-mismatched, HLA-haploidentical or Matched Unrelated Bone Marrow for Patients With Refractory SLE
Brief Summary The main goal of the study is to determine if bone marrow transplant (BMT) from a less specific pool of donors in combination with high dose cyclophosphamide can induce remission of refractory systemic lupus erythematosus.
Detailed Description

Systemic lupus erythematosus (SLE) is a devastating systemic autoimmune disease that predominantly affects young women, is more common in African-Americans than in whites, and results in poor quality of life. Lupus has no cure, and up to 90% of patients require corticosteroids for disease control. More than half of patients with lupus have permanent organ damage, much of which is either directly due to or increased by corticosteroids. To satisfactorily manage moderate-to-severe SLE, the investigators need effective treatments that will allow corticosteroid-sparing.

High-dose chemotherapy followed by autologous BMT or peripheral blood progenitor transplantation (PBSCT) has been proposed as a novel approach to treat severe autoimmune diseases. Allogeneic BMT is not currently utilized for the routine treatment of SLE because of the significant morbidity (GVHD) and mortality associated with the procedure.

The investigators have recently developed an approach to BMT using post-transplant cyclophosphamide that allows us to safely perform allogeneic BMT from matched, mismatched, unrelated or haploidentical donors. Transplant-related mortality, graft-failure and risk of GVHD have been very low with this approach. Furthermore, this approach allows us to greatly expand the donor pool since any patient shares exactly one HLA haplotype with each biological parent or child and half of siblings, an eligible haploidentical donor can be identified rapidly in nearly all cases.

This trial will employ a fludarabine + cyclophosphamide conditioning along with posttransplantation cyclophosphamide on for patients with refractory SLE. The purpose of this trial is to improve the salvage rate for patients with refractory SLE through a reformatting of the immune system.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Lupus Erythematosus
  • Graft-versus-host Disease
Intervention  ICMJE
  • Drug: Cyclophosphamide
    14.5 mg/kg/day on Days -6 and -5. 50 mg/kg/day on Days 3 and 4.
    Other Names:
    • Cytoxan
    • Cy
  • Drug: Fludarabine
    30 mg/m^2/day on Days -6 through -2.
    Other Name: Fludara
  • Drug: Tacrolimus
    Starting on Day 5. Dose will be adjusted according to blood levels.
    Other Names:
    • FK-506
    • Prograf
  • Drug: Mycophenolate Mofetil
    15 mg/kg three times per day from Day 5 to Day 35.
    Other Names:
    • Cellcept
    • MMF
  • Drug: Rabbit antithymocyte globulin
    0.5 mg/kg on Day -9. 2 mg/kg/day on Days -8 and -7.
    Other Name: Thymoglobulin
  • Radiation: Total body irradiation
    200 centigray on Day -1.
  • Biological: Allogeneic bone marrow transplant
    Infusion on Day 0.
    Other Name: BMT
Study Arms  ICMJE Experimental: Nonmyeloablative Conditioning and BMT
Nonmyeloablative conditioning with rabbit antithymocyte globulin, cyclophosphamide, fludarabine, and total body irradiation. Allogeneic bone marrow transplant on Day 0. Graft versus host disease (GVHD) prophylaxis with cyclophosphamide, mycophenolate mofetil, and tacrolimus.
Interventions:
  • Drug: Cyclophosphamide
  • Drug: Fludarabine
  • Drug: Tacrolimus
  • Drug: Mycophenolate Mofetil
  • Drug: Rabbit antithymocyte globulin
  • Radiation: Total body irradiation
  • Biological: Allogeneic bone marrow transplant
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: July 19, 2017)
1
Original Estimated Enrollment  ICMJE
 (submitted: March 4, 2014)
25
Actual Study Completion Date  ICMJE March 29, 2017
Actual Primary Completion Date March 28, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Four or more American College of Rheumatology (ACR) criteria for the classification of SLE or 4 or more of the SLICE criteria
  • Involvement of one or more of the following organ systems: renal, neurologic, hematologic, cardiac, pulmonary, gastrointestinal
  • A lack of response to corticosteroids in moderate-to-high doses, and to either an equivalent degree of immunosuppression with azathioprine, methotrexate, cyclosporin, tacrolimus, belimumab, rituximab, mycophenolate mofetil, and/or appropriate other treatment
  • Patients should be eligible for transplantation according to the BMT Policy Manual

Exclusion Criteria:

  • Age less than 18 years and over 75 years
  • Any risk of pregnancy
  • Patients who are preterminal or moribund
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02080195
Other Study ID Numbers  ICMJE J13134
NA_00082453 ( Other Identifier: Johns Hopkins IRB )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study Sponsor  ICMJE Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators  ICMJE Maryland Stem Cell Research Fund
Investigators  ICMJE
Principal Investigator: Javier Bolaños-Meade, MD The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
PRS Account Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP