Cyclophosphamide and Rabbit Antithymocyte Globulin (rATG)/Rituximab in Patients With Systemic Lupus Erythematosus

NCT00278538 | Completed Phase 2 Results DMC

• 1 other identifier: DI SLE.Auto2003
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

Brief Summary

This study is designed to examine whether treating patients with lupus with high dose cyclophosphamide together with rATG/rituximab (drugs which reduce the function of the immune system), followed by return of their previously collected stem cells will result in improvement in the disease. Stem cells are undeveloped cells that have the capacity to grow into mature blood cells, which normally circulate in the blood stream. The purpose of the intense chemotherapy is to destroy the cells in the immune system which may be causing this disease. The purpose of the stem cell infusion is to produce a normal immune system that will no longer attack body. The study purpose is to examine whether this treatment will result in improvement in the lupus disease.

Conditions

Systemic Lupus Erythematosus

Keywords

Stem cell, Autoimmune disease, Systemic Lupus Erythematosus

Outcome Measures

Primary Outcomes (1)

• Survival

  The primary efficacy outcome is overall survival.

  6 months, then yearly x 5 years after transplant

Study Arms (1)

Hematopoietic Stem Cell Transplant Regimen 2

EXPERIMENTAL

Autologous Hematopoietic Stem Cell Transplantation: Rituximab, rATG and Cyclophosphamide regimen

Biological: Hematopoietic stem cell transplantation

Interventions

Hematopoietic stem cell transplantation BIOLOGICAL

Autologous hematopoietic stem cell transplantation

Hematopoietic Stem Cell Transplant Regimen 2

Eligibility Criteria

• Age: 15 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Ages 15 to 60 years old
• Meet at least 4 of 11 American College of Rheumatology (ACR) Classification criteria for systemic lupus erythematosus (SLE) (see Appendix 16.2)
• Meet one of following five:
• For lupus nephritis, participants must fail pulse cyclophosphamide (500 to 1000 mg/m2 monthly for a minimum of 6 months). Failure is defined as meeting criteria to be considered as BILAG renal category A.
• For visceral organ involvement other than nephritis, participants must be BILAG cardiovascular/respiratory category A, vasculitis category A, or neurologic category A and must fail at least 3 months of oral or IV cyclophosphamide and be corticosteroid dependent. Steroid dependence being defined as at least 3 months of steroid therapy and inability to wean corticosteroid to less than 20 mg/day of prednisone or equivalent.
• For cytopenias that are immune mediated, participants must be BILAG hematologic category A. Participants must fail corticosteroids (either oral prednisone \> 0.5 mg/kg/day for more than 6 months or pulse methylprednisolone for at least one cycle of three days), and at least one of the following: azathioprine at 2 mg/kg/day for at least 3 months, mycophenolate mofetil 2 grams daily for more than 3 months, cyclophosphamide intravenously or orally for at least 3 months, or cyclosporine at least 3 mg/kg/day for at least 3 months, danazol for at least 3 months, or splenectomy.
• For mucocutaneous disease, participants must meet BILAG mucocutaneous category A, be unable to be weaned from prednisone to less than 0.5 mg/kg/day for more than 6 months and obvious cushingoid habitus, and have received at least one of the following: azathioprine at 2 mg/kg/day for at least 3 months, methotrexate at 15mg/week for at least 3 months, cyclophosphamide intravenously or orally for at least 3 months, or cyclosporine at least 3 mg/kg/day for at least 3 months.
• For arthritis/myositis, participants must meet BILAG musculoskeletal category A, be unable to be weaned from prednisone to less than 0.5 mg/kg/day for more than 6 months and obvious cushingoid habitus, and have received at least one of the following: azathioprine at 2 mg/kg/day for at least 3 months, methotrexate at 15mg/ week for at least 3 months, cyclophosphamide intravenously or orally for at least 3 months, or cyclosporine at least 3 mg/kg/day for at least 3 months.
• Able to give informed consent.
• If indication for hematopoietic stem cell transplant (HSCT) is nephritis, a renal biopsy must demonstrate the potential of a reversible (non-fibrotic) component indicating that if successful the participant would not be likely to be permanently dialysis-dependent after transplant.
• Since the BILAG is only one of multiple indices for SLE, patients may also be candidates if despite prior immune suppression therapy as described above, patients are still on active immune suppression (more than 10mg a day of prednisone).
• Patients with SLE whose major manifestation is Antiphospholipid syndrome (APS) may be candidates without prior immune suppression therapy if they have had a visceral organ thrombotic or embolic event despite anticoagulation.
• Patients with SLE whose major manifestation is Antiphospholipid syndrome (APS) may be candidates without prior immune suppression therapy if they have had a visceral organ thrombotic or embolic event despite anticoagulation.

You may not qualify if:

• HIV positive
• Ongoing malignancy except localized basal cell or squamous skin cancer. Other malignancies for which the participant is judged to be cured by local surgical therapy, such as head and neck cancer, or stage I or II breast cancer will be considered on an individual basis by the investigators doing the final screening for participant qualification.
• Positive pregnancy test, inability or unwillingness to pursue effective means of birth control, failure to willingly accept or comprehend irreversible sterility as a side effect of therapy.
• Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible.
• Diffusing capacity of lung for carbon monoxide (DLCO) \< 45% of predicted unless attributed to active lupus.
• Resting left ventricular ejection fraction (LVEF) \< 40% unless attributed to active lupus.
• Known hypersensitivity to E Coli derived proteins.
• Transaminases greater than 2 times normal unless attributed to active lupus.
• Positive tuberculosis skin test
• Any active infection
• Any co-morbid illness that in the opinion of the investigator would jeopardize the ability of the subject to tolerate the study.
• Failure to collect at least 2.0 x 106 cluster of differentiation 34 (CD34+) cells/kg
• Antinuclear antibody (ANA)-negative

Sponsors & Collaborators

• Northwestern University: lead

Study Sites (2)

Northwestern University, Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Related Publications (2)

• Burt RK, Han X, Gozdziak P, Yaung K, Morgan A, Clendenan AM, Henry J, Calvario MA, Datta SK, Helenowski I, Schroeder J. Five year follow-up after autologous peripheral blood hematopoietic stem cell transplantation for refractory, chronic, corticosteroid-dependent systemic lupus erythematosus: effect of conditioning regimen on outcome. Bone Marrow Transplant. 2018 Jun;53(6):692-700. doi: 10.1038/s41409-018-0173-x. Epub 2018 May 31.

  PMID: 29855561 BACKGROUND

• Burt RK, Craig RM, Milanetti F, Quigley K, Gozdziak P, Bucha J, Testori A, Halverson A, Verda L, de Villiers WJ, Jovanovic B, Oyama Y. Autologous nonmyeloablative hematopoietic stem cell transplantation in patients with severe anti-TNF refractory Crohn disease: long-term follow-up. Blood. 2010 Dec 23;116(26):6123-32. doi: 10.1182/blood-2010-06-292391. Epub 2010 Sep 13.

  PMID: 20837778 DERIVED

Related Links

• Bone Marrow Transplant

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Autoimmune Diseases

Interventions

Hematopoietic Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: Kathleen Quigley
• Organization: Northwestern University

k-quigley@northwestern.edu

312-695-8192

Study Officials

• Richard Burt, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: January 15, 2006
• First Posted: January 18, 2006
• Study Start: September 23, 2005
• Primary Completion: December 1, 2018
• Study Completion: May 1, 2019
• Last Updated: February 28, 2020
• Results First Posted: February 28, 2020

Record last verified: 2019-11

Locations

US (2)