Rituximab for GVHD

• Status: Withdrawn
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Baylor College of Medicine
• Treatments: Rituximab

Criteria

Inclusion Criteria:

1. Diagnosis of acute graft-versus-host disease (aGVHD)

2. 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.

3. 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.

4. 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).

5. ANC greater than 500/uL x 3 days (must have evidence of engraftment).

6. Patient is <100 days posttransplant

7. Any age, sex, ethnicity.

8. Karnofsky score/Lansky score of greater than 20

9. 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.

10. Parent(s)/legal guardian must give informed consent.

Exclusion Criteria:

1. Chronic GVHD (defined as GVHD occurring beyond 100 days of the hematopoietic transplant).

2. Isolated upper gastrointestinal GVHD as sole manifestation of acute GVHD.

3. Isolated grade I or II skin GVHD as sole manifestation of aGVHD.

4. GVHD following donor lymphocyte infusion (DLI).

5. 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.

6. Use of rituximab in the conditioning regimen for hematopoietic transplant.

7. Prophylactic immunosuppression tapered or stopped for treatment of leukemia relapse or minimal residual disease.

8. Patients with uncontrolled infection(s) i.e. documented bacterial, viral or fungal infection within 72 hours prior to study entry. Neither continuation of antibiotics for a controlled infection nor prophylactic/empiric antibiotics warrant exclusion. Patients with a C. difficile infection will not be excluded.

9. 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.

10. 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.

11. Mechanical ventilatory support.

12. Relapsed, refractory, or second malignancies at the time of study entry.

13. Previous grade IV severe adverse reaction to rituximab.

14. Any allergy to murine products.

15. Documented HIV or HBV infection.

16. 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.

18. Autologous or syngeneic transplants.