Ignite Creation Date:
2024-05-05 @ 4:35 PM
Last Modification Date:
2024-10-26 @ 9:22 AM
Study NCT ID:
NCT00278629
Status:
COMPLETED
Last Update Posted:
2020-07-23
First Post:
2006-01-16
Brief Title:
Hematopoietic Stem Cell Transplantation in Chronic Inflammatory Demyelinating Polyneuropathy
Sponsor:
Northwestern University
Organization:
Northwestern University
Study Overview
Official Title:
Non-myeloablative Autologous Hematopoietic Stem Cell Transplantation in Patients With Chronic Inflammatory Demyelinating Polyneuropathy A Phase II Trial
Status:
COMPLETED
Status Verified Date:
2020-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Chronic inflammatory demyelinating polyneuropathy is disease believed to be due to immune cells cells which normally protect the body but are now attacking the nerves in the body As a result the affected nerves fail to respond or respond only weakly to stimuli causing numbing tingling pain and progressive muscle weaknessThe likelihood of progression of the disease is high This study is designed to examine whether treating patients with high dose cyclophosphamide a drug which reduces the function of the immune system and ATG a protein that kills the immune cells that are thought to be causing disease followed by return of the previously collected blood stem cells will stop the progression of CIDP 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 high dose cyclophosphamide and ATG is to destroy the cells in the immune system The purpose of the stem cell infusion is to evaluate whether this treatment will produce a normal immune system that will no longer attack the body
Detailed Description:
Selection of the Regimen for Immunosuppressive Therapy
Cyclophosphamide with ATG is a common conditioning regimen with two decades of experience in the treatment of aplastic anemia and has been used safely without reported mortality in the treatment of autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritisCy ATG is not associated with late malignancies or cataracts Both cyclophosphamide and anti-thymocyte globulin horse or rabbit ATG are potent immunosuppressive agents ATG contributes additional immunosuppression without additional cytotoxicity ATG given shortly pre-transplant will contribute to the elimination of host T lymphocytes that survive cyclophosphamide SLE an autoimmune disease responsive to cyclophosphamide responds well to a CY ATG conditioning regimen but we have recently found that patients with either systemic lupus erythematosus SLE or neuromyelitis optica respond faster and may have more durable remissions to a regimen of rituxan sandwich in which rituxan is infused before and after standard cytoxan rATG For these reasons rituxan sandwich will be the conditioning regimen utilized in this study
52 Method of Harvesting Stem Cells
Based on the experience of the pilot studies the current protocol will mobilize stem cells with granulocyte-colony stimulating factor G-CSF and collect stem cells by apheresis with subsequent bone marrow harvest performed only if needed to supplement the peripheral blood stem cells PBSC Based on experience of autoimmune flares in patients receiving G-CSF alone for mobilization patients will be mobilized with cyclophosphamide 20 gm2 and G-CSF 5-10 mcgkg
53 Cyclophosphamide
Cyclophosphamide CY is an active agent in patients with a wide variety of malignancies It is used frequently in the therapy of lymphoid malignancies and has potent immunosuppressive activity It is frequently used as a cytotoxic and immunosuppressive agent in patients undergoing marrow transplants and as a treatment for patients with autoimmune diseases It is an alkylating agent that requires hepatic metabolism to the active metabolites phosphoramide mustard and acrolein These active metabolites react with nucleophilic groups It is available as an oral or intravenous preparation Bioavailability is 90 when given orally The half-life of the parent compound is 53 hours in adults and the half-life of the major metabolite phosphoramide mustard is 85 hours Liver or renal dysfunction will lead to prolonged serum half-life CY is administered intravenously at a dosage of 50 mgkg on each of 4 successive days use adjusted ideal body weight if patients actual body weight is greater than 100 ideal body weight The major dose limiting side effect at high doses is cardiac necrosis Hemorrhagic cystitis can occur and is mediated by the acrolein metaboliteThis can be prevented by co-administration of MESNA or bladder irrigation Other notable side effects include nausea vomiting alopecia myelosuppression and SIADH Refer to institutional manuals for more information about administration toxicity and complications
54 Rabbit-Derived Anti-Thymocyte Globulin rATG
Rabbit-derived anti-human thymocyte globulin rATG is a gamma globulin preparation obtained from hyperimmune serum of rabbits immunized with human thymocytes rATG has been used predominately in solid organ transplant immunosuppressive regimens rATG is a predominantly lymphocyte-specific immunosuppressive agent It contains antibodies specific to the antigens commonly found on the surface of T cells After binding to these surface molecules rATG promotes the depletion of T cells from the circulation through mechanisms which include opsonization and complement-assisted antibody-dependent cell-mediated cytotoxicity The plasma half-life ranges from 15 12 days rATG is administered intravenously at a dose of 05 mgkg recipient body weight on day -6 and at a dose of 10 mgkg recipient body weight on days -5 -4 -3 -2 and -1 Unlike equine ATG rabbit ATG does not require a pre-infusion skin test to check for hypersensitivity Methylprednisolone 250 mg will be given before every dose of rATG Additional medications such as diphenhydramine may be given at the discretion of the attending physician Although rare the major toxicity is anaphylaxis chills fever pruritus or serum sickness may occur
55 Rituxan Rituximab is a chimeric monoclonal antibody used in the treatment of B cell non-Hodgkins lymphoma B cell leukemia and numerous autoimmune disorders The recommended adult dosage for patients with low grade or follicular non-Hodgkins lymphoma NHL is 375 mgm2 infused intravenously and for adult patients with autoimmune diseases a standard 500 mg is generally given intravenously The infusion may be given at weekly intervals for four total dosages or once every 2 weeks and repeated 2-3 times Acetaminophen and diphenhydramine hydrochoride are given 30-60 minutes before the infusion to help reduce side effects If given as a retreatment the dosage is the same The majority of side effects occur after or during the first infusion of the drug Some common side effects include dizziness feeling of swelling of tongue or throat fever and chills flushing of face headache itching nausea and vomiting runny nose shortness of breath skin rash and fatigue
Cyclophosphamide with ATG is a common conditioning regimen with two decades of experience in the treatment of aplastic anemia and has been used safely without reported mortality in the treatment of autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritisCy ATG is not associated with late malignancies or cataracts Both cyclophosphamide and anti-thymocyte globulin horse or rabbit ATG are potent immunosuppressive agents ATG contributes additional immunosuppression without additional cytotoxicity ATG given shortly pre-transplant will contribute to the elimination of host T lymphocytes that survive cyclophosphamide SLE an autoimmune disease responsive to cyclophosphamide responds well to a CY ATG conditioning regimen but we have recently found that patients with either systemic lupus erythematosus SLE or neuromyelitis optica respond faster and may have more durable remissions to a regimen of rituxan sandwich in which rituxan is infused before and after standard cytoxan rATG For these reasons rituxan sandwich will be the conditioning regimen utilized in this study
52 Method of Harvesting Stem Cells
Based on the experience of the pilot studies the current protocol will mobilize stem cells with granulocyte-colony stimulating factor G-CSF and collect stem cells by apheresis with subsequent bone marrow harvest performed only if needed to supplement the peripheral blood stem cells PBSC Based on experience of autoimmune flares in patients receiving G-CSF alone for mobilization patients will be mobilized with cyclophosphamide 20 gm2 and G-CSF 5-10 mcgkg
53 Cyclophosphamide
Cyclophosphamide CY is an active agent in patients with a wide variety of malignancies It is used frequently in the therapy of lymphoid malignancies and has potent immunosuppressive activity It is frequently used as a cytotoxic and immunosuppressive agent in patients undergoing marrow transplants and as a treatment for patients with autoimmune diseases It is an alkylating agent that requires hepatic metabolism to the active metabolites phosphoramide mustard and acrolein These active metabolites react with nucleophilic groups It is available as an oral or intravenous preparation Bioavailability is 90 when given orally The half-life of the parent compound is 53 hours in adults and the half-life of the major metabolite phosphoramide mustard is 85 hours Liver or renal dysfunction will lead to prolonged serum half-life CY is administered intravenously at a dosage of 50 mgkg on each of 4 successive days use adjusted ideal body weight if patients actual body weight is greater than 100 ideal body weight The major dose limiting side effect at high doses is cardiac necrosis Hemorrhagic cystitis can occur and is mediated by the acrolein metaboliteThis can be prevented by co-administration of MESNA or bladder irrigation Other notable side effects include nausea vomiting alopecia myelosuppression and SIADH Refer to institutional manuals for more information about administration toxicity and complications
54 Rabbit-Derived Anti-Thymocyte Globulin rATG
Rabbit-derived anti-human thymocyte globulin rATG is a gamma globulin preparation obtained from hyperimmune serum of rabbits immunized with human thymocytes rATG has been used predominately in solid organ transplant immunosuppressive regimens rATG is a predominantly lymphocyte-specific immunosuppressive agent It contains antibodies specific to the antigens commonly found on the surface of T cells After binding to these surface molecules rATG promotes the depletion of T cells from the circulation through mechanisms which include opsonization and complement-assisted antibody-dependent cell-mediated cytotoxicity The plasma half-life ranges from 15 12 days rATG is administered intravenously at a dose of 05 mgkg recipient body weight on day -6 and at a dose of 10 mgkg recipient body weight on days -5 -4 -3 -2 and -1 Unlike equine ATG rabbit ATG does not require a pre-infusion skin test to check for hypersensitivity Methylprednisolone 250 mg will be given before every dose of rATG Additional medications such as diphenhydramine may be given at the discretion of the attending physician Although rare the major toxicity is anaphylaxis chills fever pruritus or serum sickness may occur
55 Rituxan Rituximab is a chimeric monoclonal antibody used in the treatment of B cell non-Hodgkins lymphoma B cell leukemia and numerous autoimmune disorders The recommended adult dosage for patients with low grade or follicular non-Hodgkins lymphoma NHL is 375 mgm2 infused intravenously and for adult patients with autoimmune diseases a standard 500 mg is generally given intravenously The infusion may be given at weekly intervals for four total dosages or once every 2 weeks and repeated 2-3 times Acetaminophen and diphenhydramine hydrochoride are given 30-60 minutes before the infusion to help reduce side effects If given as a retreatment the dosage is the same The majority of side effects occur after or during the first infusion of the drug Some common side effects include dizziness feeling of swelling of tongue or throat fever and chills flushing of face headache itching nausea and vomiting runny nose shortness of breath skin rash and fatigue
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None