Clinical trial NCT00186628: Phase 2 Trial of Prophylactic Rituximab Therapy for Prevention of CGVHD
Official title: An Open-label, Phase 2 Trial of Prophylactic Rituximab Therapy for Prevention of Chronic Graft Versus Host Disease After TLI/ARG Nonmyeloablative Allogeneic Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia, Mast-Cell
Mantle-cell Lymphoma
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: The Leukemia and Lymphoma Society
name: National Cancer Institute (NCI)
First posted: 2005-09-16
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 76
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To determine if rituximab administered after allogeneic transplantation decreases the incidence of chronic graft-vs-host disease (cGvHD)

Detailed description: To test if prophylactic anti-B-cell therapy (weekly rituximab) given within 60 to 90 days after allogeneic transplantation will decrease allogeneic donor B-cell immunity and possibly the incidence of chronic graft-vs-host disease (cGvHD).

Eligibility criteria: Recipient Inclusion Criteria:

* Between 18 and 76 years of age
* 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

Donor Inclusion Criteria:

* 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

Recipient Exclusion Criteria:

* Recipient has a 9 of 10 or 10 of 10 HLA identical donor (high resolution molecular genotyping at HLA A, B, C and DrB1, and DQ)
* 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

Donor Exclusion Criteria:

* 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

Primary outcomes:
measure: Chronic Graft-vs-Host Disease (cGvHD)
timeFrame: 4 years
Secondary outcomes:
measure: Incidence of Relapse
timeFrame: 4 years
measure: Mortality
timeFrame: Day 100 and 1 year
measure: Overall Survival
timeFrame: 4 years
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
Study officials:
affiliation: Stanford University
name: David Miklos
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.