Allogeneic Stem Cell Transplantation in Systemic Lupus Erythematosus

Systemic Lupus Erythematosus Clinical Trial

Official title: Allogeneic Stem Cell Transplantation in Patients With Systemic Lupus Erythematosus

Status Withdrawn

Clinical Trial Summary

This trial is designed to evaluate the safety of treating systemic lupus erythematosus participants with cyclophosphamide and CAMPATH-1H followed by allogeneic stem cell transplant. There will be no randomization in this study. All subjects who are determined to be eligible for the study treatment will receive cyclophosphamide and CAMPATH-1H followed by allogeneic stem cell transplant. 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.

Clinical Trial Description

This phase I study is designed to select patients with refractory and intractable disease. SLE patients with impaired visceral organ function and chronic exposure to glucocorticoid therapy are complicated by significant morbidity, frequent hospitalizations and high-risk of mortality. For participants in whom the indication is nephritis, active disease must be present despite at least 6 cycles of monthly pulse cyclophosphamide. Participants with extra-renal lupus need to fail 3 months of monthly cyclophosphamide. Patients who have an HLA matched sibling, will be offered allogeneic HSCT. Because of high transplant related toxicity and mortality in conventional myeloablative regimens, we will utilize a mini-conditioning regimen. To minimize GvHD, candidates must be 50 years old or younger and in vivo CAMPATH will be used in the conditioning regimen to deplete infused donor lymphocytes.

Peripheral Blood Stem Cell (PBSC) Harvest from Donor PBSC will be mobilized with G-CSF 10 mcg/kg/day (dose may be adjusted to 5-16 mcg/kg/day by PI for toxicity, e.g. flu-like symptoms) with stem cell collection beginning on day 4. Leukapheresis may be repeated up to three consecutive days.

1) If these criteria are not meet the patient (recipient) may not be treated.

1. CD34+ cell count >2.0 x106 CD34+ cells/kg recipient weight

2. Gram stein negative

3. Culture negative ( after 14 days)

4. Cell viability at time of final formulation in cyroprotectant media≥ 70% Conditioning Regimen Cyclophosphamide 50mg/kg/day x 4 days will be given IV over 1 hour in 500 cc of normal saline. If actual weight is < ideal weight, cyclophosphamide will be given based on actual weight. If actual weight is > ideal weight, cyclophosphamide will given as adjusted weight. Adjusted weight = ideal weight + 25% (actual weight minus ideal weight).

Mesna 50mg/kg/day will be given IV over 24 hours in 250 cc of normal saline or D5W starting 2 hours before the first cyclophosphamide dose. Weight base is calculated same as cyclophosphamide as above.

Hydration approximately 50-200cc/hour in adults should begin 6 hours before cyclophosphamide and continue until 24 hours after the last cyclophosphamide dose. Hydration rates need to be individually adjusted by daily weights to maintain dry weight count. BID weights will be obtained. Warning: Participants with renal insufficiency are prone to volume overload. Early institution of ultra filtration or dialysis is recommended. Three-way bladder irrigation may be needed for those participants who cannot tolerate fluid hydration during cyclophosphamide administration and for 24 hours after the last dose of cyclophosphamide. In patients on hemodialysis, cyclophosphamide will be given in the evening and hemodialysis will be performed in the morning daily until the last dose of cyclophosphamide is administered. Close coordination with nephrology service is required.

CAMPATH-1H 30mg/day x 2 days (no dose adjustment) will be given IV over 2 hours in 100 cc of normal saline. Premedication with acetaminophen 650mg and benadryl 50mg PO/IV will be given 30-60min before infusion. These medications can be repeated as needed. Solumedrol 1 gram will be given IV 30 min prior to CAMPATH-1H.

G-CSF 5 mcg/kg/day will be started on day 6 if engraftment has not occurred. It will be continued until absolute neutrophil count reaches at least 500/ul. The dose may be rounded up or down in order to not waste medication in the vial. NOTE: GCSF may be started earlier, e.g. day 0, per investigator's discretion.

Cyclosporine* will be started on day -3 at 200 mg po BID and adjusted by HPLC levels to between 150 - 250 or by toxicity (e.g., tremor, renal insufficiency, TTP, etc.). CSA will be continued for 2 months unless stopped for toxicity. If patient cannot tolerate oral cycloporine, intravenous cyclosporine continuous infusion (3mg/kg/24hours) and adjusted by levels can be used.

Mycophenolate mofetil (MMF)* 1g PO/IV q 12 hrs will be started on day -3 and continued for 6 months. The dosage will be adjusted and tapered off before stopping, unless toxicity mandates abrupt cessation. MMF will be adjusted by PI according to toxicity, GVHD, and donor engraftment or donor chimerism.

*Cyclosporine and MMF guidelines dosage and duration can be modified according to investigators discretion based on side effects, renal function, CBC and GVHD status. ;

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

• NCT number: NCT00278590
• Study type: Interventional
• Source: Northwestern University
• Status: Withdrawn
• Phase: Phase 1
• Start date: July 2004
• Completion date: July 2015