Rituximab for GVHD

NCT00578591 | Withdrawn Phase 2 DMC

• 2 other identifiers: 19734RITUXIMAB GVHD
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

This is a prospective, open-label pilot study in which 4 doses of Rituximab are administered to patients who have developed SR-aGVHD following allogeneic hematopoietic transplant (AHT). The study is designed to determine the overall survival at 180 days after treatment with rituximab, and evaluates the safety and clinical response to rituximab in this study population. Study entry: Patients must enter study on or before day +100 posttransplant.

Conditions

Graft vs Host Disease; Alogenic Hematopoietic Transplant

Keywords

Graft Versus Host Disease; GVHD; allogeneic hematopoietic transplant; AHT; posttransplant; Rituximab

Outcome Measures

Primary Outcomes (1)

• Complete response rate at 4 and 8 weeks in patients with SR-GVHD treated with Rituximab.

  2 months

Secondary Outcomes (13)

• Survival at day 180 after txt with rituximab.

  6 months

• Partial response rates at 4 weeks and 8 weeks, mixed response rate, and disease progression in patients treated with these regimens.

  2 months

• Treatment failure rate at 2 weeks (no response, progression, or mortality).

  2 weeks

• Safety of rituximab in SR-GVHD

  2 years

• Time to aGVHD improvement.

  2 years

Study Arms (1)

Patient

EXPERIMENTAL

Four Rituximab doses administered to patients who have developed SR-aGVHD following allogeneic hematopoietic transplant (AHT)

Drug: Rituximab

Interventions

Rituximab DRUG

Rituximab 375 mg/m\^2 is given weekly X 4. For patients with a partial response, an additional 4 doses will be permitted as needed (after 4 weeks from the last dose). Diagnosis of grade II to IV aGVHD will be confirmed, whenever possible, by a biopsy taken from at least one of the following three sites: skin, gut, or liver.

Patient

Eligibility Criteria

• Age: Up to 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of acute graft-versus-host disease (aGVHD)
• Steroid-refractory aGVHD with any of the following: a) No change in the stage of skin aGVHD after 1 week of 2 mg/kg per day or more methylprednisolone. b) Progression of acute GVHD (ie, increase in disease stage by at least 1) of skin GVHD or lack of response of visceral (liver, GI) aGVHD despite treatment with 2 mg/kg per day or more methylprednisolone for at least 72 hours. c) Progression of visceral aGVHD despite treatment with 2 mg/kg per day or more methylprednisolone for at least 48 hours d) Visceral aGVHD progressing to stage 4 after 24 hours of 2 mg/kg per day or more methylprednisolone.
• Grade II-IV aGVHD requiring systemic therapy within 24-48 hours of diagnosis. Biopsy confirmation of aGVHD is strongly recommended but not required; enrollment should not be delayed awaiting biopsy or pathology results.
• Patients must have received corticosteroids at greater than or equal to 2 mg/kg/day for a minimum of 72 hours prior to study entry (first-line aGVHD treatment).
• ANC greater than 500/uL x 3 days (must have evidence of engraftment).
• Patient is \<100 days posttransplant
• Any age, sex, ethnicity.
• Karnofsky score/Lansky score of greater than 20
• Men and women of child-bearing potential must use adequate birth control measures (e.g., abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, or surgical sterilization) for the duration of the study and should continue such precautions for 6 months after receiving the study drug infusion.
• Parent(s)/legal guardian must give informed consent.

You may not qualify if:

• Chronic GVHD (defined as GVHD occurring beyond 100 days of the hematopoietic transplant).
• Isolated upper gastrointestinal GVHD as sole manifestation of acute GVHD.
• Isolated grade I or II skin GVHD as sole manifestation of aGVHD.
• GVHD following donor lymphocyte infusion (DLI).
• Other investigational agents for the treatment or prophylaxis of GVHD within the past 2 weeks. An investigational drug is defined as one that is being given on study, requiring informed consent.
• Use of rituximab in the conditioning regimen for hematopoietic transplant.
• Prophylactic immunosuppression tapered or stopped for treatment of leukemia relapse or minimal residual disease.
• Patients with any one of the following opportunistic infections documented within 8 weeks prior to study entry are excluded: pneumocystis carinii, aspergillosis, histoplasmosis, atypical mycobacterium infection or other pathogenic molds/fungi.
• Patients with hypotension believed to be secondary to sepsis syndrome or heart failure requiring \> 1 inotropic agent, or dopamine \>5mcg/kg/minute for blood pressure support.
• Mechanical ventilatory support.
• Relapsed, refractory, or second malignancies at the time of study entry.
• Previous grade IV severe adverse reaction to rituximab.
• Any allergy to murine products.
• Documented HIV or HBV infection.
• Patients with grade IV renal, hepatic, pulmonary, or neurologic toxicity by National Cancer Institute (NCI) Common Toxicity Criteria (CTC). 17. Patients with history of congestive heart failure, defined as cardiac dysfunction requiring inotropic support other than dopamine at \<= 5mcg/kg/minute.

Sponsors & Collaborators

• Baylor College of Medicine: lead

Study Sites (2)

Methodist Hospital

Houston, Texas, 77030, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Rammurti Kamble, MD

  Baylor College of Medicine/TCH/Methodist

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 19, 2007
• First Posted: December 21, 2007
• Study Start: June 1, 2007
• Last Updated: July 9, 2012

Record last verified: 2012-07

Locations

US (2)