A Phase 2 Trial of Rituximab and Corticosteroid Therapy for Newly Diagnosed Chronic Graft Versus Host Disease

The addition of rituximab to prednisone for the initial treatment of chronic GVHD will increase the overall response rate, enable a more rapid and effective steroid taper.

Study Overview

• Status: Completed
• Conditions: Graft vs Host Disease
• Intervention / Treatment: Drug: Rituximab; Drug: Prednisone; Drug: Cyclosporine A; Drug: tacrolimus

Detailed Description

To determine the efficacy of Rituximab as first line of treatment of chronic GVHD. Efficacy will be defined as he ability to taper prednisone to a dose of 0.25 mg/kg per day by 6 months without clinical or GVHD relapse/ recurrence.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Children and adults with a new diagnosis of chronic GVHD- that requires systemic immunosuppressive treatment to a dose of 1mg/kg/day prednisone and who have undergone any type of donor hematopoietic cell graft or conditioning regimen.
• Stable doses of other immunosuppressive medications (e.g. calcineurin inhibitors, mycophenolate mofetil) for 2 weeks prior to enrollment. In addition, these other immunosuppressive medications should not be dose increased.
• 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.

Exclusion Criteria:

• Known life-threatening hypersensitivity to Rituximab or other anti-B cell antibody.
• Treatment with prednisone (or equivalent) at doses higher than 1 mg/kg/day at the time of enrollment. Persistent prednisone treatment of acute GVHD that is less than 1mg/kg is allowed.
• Active, uncontrolled infection- CMV reactivation is excluded (i.e. pneumonitis, colitis). Peripheral blood CMV reactivation is allowed as long as it is not associated with CMV disease and is responding to therapy.
• Known Hepatitis B surface Ag positive
• Active malignant disease relapse.
• Pregnancy
• Lactating
• Inability to comply with the Rituximab treatment regimen.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: rituximab + prednisone arm; Rituximab will be given as an IV fusion as initial treatment, followed by predisone (given during registration) which will be continued through-out trial and tapered off by physician. Cyclosporine A and tacrolimus will be used if chances of new diagnosis of chronic GVHD occur. Both drugs have no interaction with Rituxan, but will be tapered off after predisone is completely tapered.

Drug: Rituximab; 375 mg/m2;IV infusion once weekly for four doses (days 1,8,15,22); option for second 4-week course at week 9; Other Names: Rituxan; Drug: Prednisone; 1 mg/kg; po per day with taper; Other Names: Deltasone; Orasone; Meticorten; Liquid Pred; Drug: Cyclosporine A; trough 200-300 or lower; po; Other Names: Ciclosporin; cyclosporine; Drug: tacrolimus; trough 5-10 or lower; po; Other Names: Fujimycin; FK-506

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With the Ability to Successfully Taper Prednisone to a Dose Lower Dose.	Participants that have successfully tapered prednisone to a dose of 0.25 mg/kg/Day by 6 Months without clinical relapse.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Complete and/or Partial GVHD Response	To have physician documentation of clinical GVHD response using organ staging and scoring scale- NIH clinical GVHD consensus response criteria applied 6 months after rituximab infusion began	6 months
Participants Who Reduced Steroid Use at One Year After Enrollment on the Trial	Participants that decreased total daily corticosteroids ≤ 0.25mg/kg one year after rituximab infusion began	1 year
Failure-free Survival at 6 and 12 Months Post-Rituximab Initiation	Failure-free survival (FFS) was defined as participants who are surviving with no relapse and second line of cGVHD treatment.	6 and 12 Months
Overall Survival	Overall survival at 6 and 12 months	6 and 12 months

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Principal Investigator: Sally Arai, Stanford University

Study record dates

Study Major Dates

• Study Start: August 1, 2006
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: July 5, 2006
• First Submitted That Met QC Criteria: July 5, 2006
• First Posted (Estimate): July 10, 2006

Study Record Updates

• Last Update Posted (Actual): November 20, 2017
• Last Update Submitted That Met QC Criteria: October 19, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Immunological; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Rituximab; Prednisone; Tacrolimus; Cyclosporine; Cyclosporins
• Other Study ID Numbers: IRB-04948; 96950 (Other Identifier: Stanford University alternate IRB Number); BMT177 (Other Identifier: OnCore); NCI-2011-00450 (Other Identifier: National Cancer Institute (NCI))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD will be available in the publication which is forthcoming.