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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT00278538
• Date of registration: 15/01/2006
• Prospective Registration: No
• Primary sponsor: Northwestern University
• Public title: Cyclophosphamide and Rabbit Antithymocyte Globulin (rATG)/Rituximab in Patients With Systemic Lupus Erythematosus
• Scientific title: Cyclophosphamide and rATG/Rituximab in Patients With Systemic Lupus Erythematosus: Phase II Trial
• Date of first enrolment: September 23, 2005
• Target sample size: 32
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00278538
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Richard Burt, MD
• Affiliation: Northwestern University

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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:

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

Exclusion Criteria:

- 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



Age minimum: 15 Years
Age maximum: 60 Years
Gender: All

Health Condition(s) or Problem(s) studied

Systemic Lupus Erythematosus

Intervention(s)

Biological: Hematopoietic stem cell transplantation

Primary Outcome(s)

Survival [Time Frame: 6 months, then yearly x 5 years after transplant]

Secondary ID(s)

DI SLE.Auto2003

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 28/02/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00278538