Phase 2 Trial of Prophylactic Rituximab Therapy for Prevention of CGVHD
NCT ID: NCT00186628
Last Updated: 2017-11-28
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
36 participants
INTERVENTIONAL
2005-06-30
2010-12-31
Brief Summary
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Detailed Description
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Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Prophylactic Rituximab
Rituximab will be infused after a non-myeloablative transplantation regimen of total lymphoid irradiation (TLI) + anti-thymoglobulin (ATG), with the intention of reducing chronic graft-vs-host disease (cGvHD)
Total lymphoid irradiation
Total lymphoid irradiation (TLI) administered at 80cGy for 10 days
Rituximab
Rituximab 375 mg/m2 administered as an intravenous (IV) infusion once weekly for 4 doses.
Anti-thymoglobulin, rabbit (ATG, rabbit ATG)
Rabbit anti-thymoglobulin (ATG) administered from Day -11 through Day -7 (5 doses) at 1.5 mg/kg/day, for a total dose of 7.5 mg/kg.
Cyclosporine
Cyclosporine (CSP) administered orally at 6.25 mg/kg twice-a-day (BID) from Day -3 until through Day +56 post-peripheral blood progenitor cell (PBPC) infusion. Dose may be adjusted to maintain a therapeutic level of cyclosporine, or in response to renal insufficiency. If at Day +56, chimerism assessment demonstrates \> 40% donor cells in the CD3+ lineage, and the patient is without evidence of GvHD, then cyclosporine taper will begin (6% reduction per week).
Mycophenylate mofetil
Mycophenylate mofetil (MMF) will be administered at 15 mg/kg po Day 0, at 5 to 10 hours after mobilized PBPC infusion is complete
Filgrastim
Filgrastim provided as needed for neutrophil support
Granisetron
Granisetron administered as an anti-nausea agent (anti-emetic) at 1 mg orally 30 to 60 minutes before TLI
Solumedrol
Solumedrol, an anti-inflammatory glucocorticoid containing methylprednisolone sodium succinate, administered at 1 mg/kg as a premedication for anti-thymoglobulin (ATG)
Acetaminophen
Acetaminophen administered orally at 650 mg 1 hour prior to infusion of PBPC
Diphenhydramine
Diphenhydramine administered by intravenous infusion at 50 mg 1 hour prior to infusion of PBPC
Hydrocortisone
Hydrocortisone administered by intravenous infusion at 100 mg 1 hour prior to infusion of PBPC
Interventions
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Total lymphoid irradiation
Total lymphoid irradiation (TLI) administered at 80cGy for 10 days
Rituximab
Rituximab 375 mg/m2 administered as an intravenous (IV) infusion once weekly for 4 doses.
Anti-thymoglobulin, rabbit (ATG, rabbit ATG)
Rabbit anti-thymoglobulin (ATG) administered from Day -11 through Day -7 (5 doses) at 1.5 mg/kg/day, for a total dose of 7.5 mg/kg.
Cyclosporine
Cyclosporine (CSP) administered orally at 6.25 mg/kg twice-a-day (BID) from Day -3 until through Day +56 post-peripheral blood progenitor cell (PBPC) infusion. Dose may be adjusted to maintain a therapeutic level of cyclosporine, or in response to renal insufficiency. If at Day +56, chimerism assessment demonstrates \> 40% donor cells in the CD3+ lineage, and the patient is without evidence of GvHD, then cyclosporine taper will begin (6% reduction per week).
Mycophenylate mofetil
Mycophenylate mofetil (MMF) will be administered at 15 mg/kg po Day 0, at 5 to 10 hours after mobilized PBPC infusion is complete
Filgrastim
Filgrastim provided as needed for neutrophil support
Granisetron
Granisetron administered as an anti-nausea agent (anti-emetic) at 1 mg orally 30 to 60 minutes before TLI
Solumedrol
Solumedrol, an anti-inflammatory glucocorticoid containing methylprednisolone sodium succinate, administered at 1 mg/kg as a premedication for anti-thymoglobulin (ATG)
Acetaminophen
Acetaminophen administered orally at 650 mg 1 hour prior to infusion of PBPC
Diphenhydramine
Diphenhydramine administered by intravenous infusion at 50 mg 1 hour prior to infusion of PBPC
Hydrocortisone
Hydrocortisone administered by intravenous infusion at 100 mg 1 hour prior to infusion of PBPC
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Chronic lymphocytic leukemia (CLL):
* Unmutated IgG VH gene status
* Mutated IgG VH genes (\> 2% nucleotide change compared to somatic sequence)
* Complete remission benefit most from allogeneic hematopoietic stem cell transplant (HSCT).
(Physicians will be encouraged to provide aggressive chemotherapy prior to nonmyeloablative transplantation.)
* Mantle cell lymphoma (MCL): Transplant physicians believe subject would benefit from allogeneic HSCT.
* Adequate renal (Cr \< 2.4 mg/dL) and hepatic (Bilirubin \< 3.0 mg/dL, Aspartate aminotransferase (AST) \< 100 IU) function.
* Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for six months after completion of treatment.
* All subjects must provide written informed consent
* Genotypically or phenotypically human leukocyte antigen (HLA)-identical.
* Age \< 76 unless cleared by institutional PI
* Capable of giving written, informed consent.
* Must consent to peripheral blood stem cell (PBSC) mobilization with G-CSF and apheresis
Exclusion Criteria
* Pregnancy
* Lactating
* Serious uncontrolled infection
* HIV seropositivity
* Hepatitis B or C seropositivity
* Cardiac function: ejection fraction \< 40% or uncontrolled cardiac failure
* Pulmonary: Diffusing capacity - carbon monoxide (DLCO) \< 50% predicted
* Liver function abnormalities: elevation of bilirubin to ≥ 3 mg/dL and/or AST \> 100
* Renal: creatinine \> 2.4
* Karnofsky performance score ≤ 60%
* Patients with poorly controlled hypertension (systolic blood pressure \> 150 or diastolic blood pressure \> 90 repeatedly).
* Known life-threatening hypersensitivity to rituximab or other anti-B cell antibodies.
* Inability to comply with the allogeneic transplant treatment.
* Uncontrolled central nervous system (CNS) involvement with disease
* Identical twin to subject
* Contra-indication to subcutaneous G-CSF at a dose of 16 mg/kg/d for 5 consecutive days
* Serious medical or psychological illness
* Prior malignancy within the preceding five years, with the exception of non-melanoma skin cancers.
* HIV seropositivity
18 Years
76 Years
ALL
No
Sponsors
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The Leukemia and Lymphoma Society
OTHER
National Cancer Institute (NCI)
NIH
Stanford University
OTHER
Responsible Party
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David Miklos
Assistant Professor of Medicine
Principal Investigators
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David Miklos
Role: PRINCIPAL_INVESTIGATOR
Stanford University
Locations
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Stanford University School of Medicine
Stanford, California, United States
Countries
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References
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Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, Martin P, Chien J, Przepiorka D, Couriel D, Cowen EW, Dinndorf P, Farrell A, Hartzman R, Henslee-Downey J, Jacobsohn D, McDonald G, Mittleman B, Rizzo JD, Robinson M, Schubert M, Schultz K, Shulman H, Turner M, Vogelsang G, Flowers ME. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005 Dec;11(12):945-56. doi: 10.1016/j.bbmt.2005.09.004.
Arai S, Sahaf B, Narasimhan B, Chen GL, Jones CD, Lowsky R, Shizuru JA, Johnston LJ, Laport GG, Weng WK, Benjamin JE, Schaenman J, Brown J, Ramirez J, Zehnder JL, Negrin RS, Miklos DB. Prophylactic rituximab after allogeneic transplantation decreases B-cell alloimmunity with low chronic GVHD incidence. Blood. 2012 Jun 21;119(25):6145-54. doi: 10.1182/blood-2011-12-395970. Epub 2012 May 4.
Other Identifiers
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IRB-02372
Identifier Type: -
Identifier Source: org_study_id
96160
Identifier Type: OTHER
Identifier Source: secondary_id
BMT172
Identifier Type: OTHER
Identifier Source: secondary_id
SPO
Identifier Type: OTHER
Identifier Source: secondary_id
NCT00234013
Identifier Type: -
Identifier Source: nct_alias