Phase 2 Trial of Prophylactic Rituximab Therapy for Prevention of CGVHD

Phase 2

Completed

• Conditions: Leukemia, Mast-Cell; Mantle-cell Lymphoma
• Interventions: Procedure: Total lymphoid irradiation; Drug: Rituximab; Drug: Anti-thymoglobulin, rabbit (ATG, rabbit ATG); Drug: Cyclosporine; Drug: Mycophenylate mofetil; Drug: Filgrastim; Drug: Granisetron; Drug: Solumedrol; Drug: Acetaminophen; Drug: Diphenhydramine; Drug: Hydrocortisone

• Registration Number: NCT00186628
• Lead Sponsor: Stanford University

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).

Study Timeline

• Study Start: 2005-06
• Study First Submitted: 2005-09-14
• Study First Submitted QC: 2005-09-14
• Study First Posted: 2005-09-16
• Primary Completion: 2010-11
• Study Completion: 2010-12
• Results First Submitted: 2016-12-12
• Status Verified: 2017-10
• Results First Submitted QC: 2017-10-20
• Last Update Submitted: 2017-10-20
• Results First Posted: 2017-11-28
• Last Update Posted: 2017-11-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Prophylactic Rituximab	Anti-thymoglobulin, rabbit (ATG, rabbit ATG)	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)
Prophylactic Rituximab	Total lymphoid irradiation	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)
Prophylactic Rituximab	Acetaminophen	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)
Prophylactic Rituximab	Mycophenylate mofetil	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)
Prophylactic Rituximab	Solumedrol	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)
Prophylactic Rituximab	Granisetron	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)
Prophylactic Rituximab	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)
Prophylactic Rituximab	Filgrastim	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)
Prophylactic Rituximab	Cyclosporine	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)
Prophylactic Rituximab	Hydrocortisone	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)
Prophylactic Rituximab	Diphenhydramine	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)

Primary Outcome Measures

Name	Time	Method
Chronic Graft-vs-Host Disease (cGvHD)	4 years	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)

Secondary Outcome Measures

Name	Time	Method
Incidence of Relapse	4 years	Subjects who Relapsed following after Allogeneic HSCT
Mortality	Day 100 and 1 year	Number of participants who died within 100 days and within 1 year, non-relapse and associated with relapse.
Overall Survival	4 years

Trial Locations

Locations (1)

Stanford University School of Medicine; 🇺🇸 Stanford, California, United States