Phase 2 Trial of Prophylactic Rituximab Therapy for Prevention of CGVHD

Mantle-cell Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00186628
• Other study ID #: IRB-02372
• Secondary ID: 96160BMT172SPOP0
• Status: Completed
• Phase: Phase 2
• First received: September 14, 2005
• Last updated: October 20, 2017
• Start date: June 2005
• Est. completion date: December 2010

Study information

• Verified date: October 2017
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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).

Other known NCT identifiers

• NCT00234013

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: December 2010
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 76 Years

Eligibility

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

Related Conditions & MeSH terms

• Leukemia, Mast-Cell
• Lymphoma, Mantle-Cell
• Mantle-cell Lymphoma

Intervention

Procedure:
• Total lymphoid irradiation
Total lymphoid irradiation (TLI) administered at 80cGy for 10 days

Drug:
• 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

Locations

Country	Name	City	State
United States	Stanford University School of Medicine	Stanford	California

Sponsors (3)

Lead Sponsor	Collaborator
Stanford University	National Cancer Institute (NCI), The Leukemia and Lymphoma Society

Country where clinical trial is conducted

United States, 

References & Publications (2)

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-ce — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Chronic Graft-vs-Host Disease (cGvHD)	The cumulative percentage of participants who develop chronic graft-vs-host disease (cGvHD). Chronic cGvHD was defined as at least one instance of a clinically-accepted marker for cGvHD (see Filipovich, et al. Biology of Blood and Marrow Transplantation. 2005;11:945-955)	4 years
Secondary	Incidence of Relapse	Subjects who Relapsed following after Allogeneic HSCT	4 years
Secondary	Mortality	Number of participants who died within 100 days and within 1 year, non-relapse and associated with relapse.	Day 100 and 1 year
Secondary	Overall Survival		4 years