Photopheresis for the Treatment of Acute Graft Versus Host Disease

NCT00609609 | Completed Phase 2 Results DMC

• 2 other identifiers: 2005-1022NCI-2012-01751
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to find out whether adding extracorporeal photopheresis (ECP) to standard therapy for acute GVHD with corticosteroids improves response to treatment, length of treatment, and survival.

Conditions

Graft Versus Host Disease

Keywords

Allogeneic stem cell grafts; Allogeneic bone marrow graft; Blood and Marrow Transplantation; Stem cell graft; Graft Versus Host Disease; GVHD; Extracorporeal Photopheresis; ECP; Photopheresis; Methylprednisolone; Medrol; Depo-Medrol; Solu-Medrol

Outcome Measures

Primary Outcomes (1)

• Day 56 Treatment Success

  Definition of Treatment Failure: No Response according to the following: A) Skin: 1) No change in GVHD stage by day 14; 2) Gut: No change in GVHD stage by Day 7; 3) Liver: No change in GVHD stage by Day 21. B) Progressive Disease (PD): 1) Skin/Gut: Increase in Stage by 72 hours from the start of therapy; 2) Liver: Increase in Stage by Day 14; 3) Initiation of 2nd line treatment at any time for acute GVHD: 4) Any new organ involvement by acute GVHD. C) Inability to Taper: 1) Patient still on \>1 mg/kg/d of methylprednisolone equivalent at 1 month. 2) Patient still on \> 0.5 mg/kg/d of methylprednisolone equivalent at 2 months; 3) Death from GVHD. Definition of Treatment Success: Participants not defined above in Treatment Failure definition. Baseline biopsy with Acute GVHD assessed weekly until last ECP procedure (anticipated Day 63). At 6 months follow up with a phone call for survival and GVHD status.

  Day 1 to Day 63 (approximately 9 weeks), Acute GVHD scored weekly.

Study Arms (2)

Corticosteroids

EXPERIMENTAL

Methylprednisolone at a dose of 2 mg/kg/day with a taper to no less than 1 mg/kg/day by day 14, and no less than 0.4 mg/kg/day by day 28.

Drug: Methylprednisolone

ECP + Corticosteroids

EXPERIMENTAL

Extracorporeal Photopheresis (ECP) 8-9 treatments weekly for days 1-14, 6 treatments weekly from days 15-28, and after that 2 treatments weekly until day 60 + Methylprednisolone at a dose of 2 mg/kg/day with a taper to no less than 1 mg/kg/day by day 14, and no less than 0.4 mg/kg/day by day 28.

Procedure: Photopheresis; Drug: Methylprednisolone

Interventions

Photopheresis PROCEDURE

8-9 photopheresis treatments weekly for days 1-14, 6 treatments weekly from days 15-28, and after that 2 treatments weekly until day 60. After day 60, your doctor will decide whether ECP is worth continuing, and the frequency of treatments.

Also known as: Extracorporeal Photopheresis, ECP

ECP + Corticosteroids

Methylprednisolone DRUG

2 mg/kg daily with a taper to no less than 1 mg/kg/day by day 14, followed by a tapering schedule according to the suggested guidelines.

Also known as: Medrol, Depo-Medrol, Solu-Medrol

Corticosteroids; ECP + Corticosteroids

Eligibility Criteria

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

You may qualify if:

• Patients must be recipients of allogeneic bone marrow or stem cell grafts.
• Patient must weigh above 40 kg
• Patients must have new onset, clinical grade II-III acute or late-acute GVHD of the GI tract or liver, or the skin that developed post transplantation. The diagnosis of GVHD must be pathologically confirmed in at least one organ or highly suspected clinically. Pathological confirmation may occur after registration and after the start of therapy. Definition of Late Acute GVHD vs Acute GVHD: The diagnosis of Late Acute GVHD includes clinical features that are identical to Acute GVHD, however, Late Acute GVHD is diagnosed on or after day 100 post transplantation.
• Continued from #3: These manifestations include a maculopapular rash, abnormal liver studies (cholestatic jaundice) and/or nausea/vomiting / diarrhea. Patients must not have any concurrent classical features of chronic GVHD in addition to the above manifestations. Features of chronic GVHD include dry eyes and mouth, contractures, and/ or sclerodermal, lichenoid skin changes.
• In the clinical judgment of the PI, patients must be able to sustain a platelet count and a hematocrit \>/= 20,000/mL and \>/= 27% respectively, with or without transfusions.
• The absolute white blood cell count (WBC) must be \>1500/mL
• Patient must be willing to comply with all study procedures.
• All patients with childbearing potential, including males and females, must commit to using adequate contraceptive precautions throughout their participation in the study and for 3 months following the last ECP treatment.

You may not qualify if:

• Patients developing chronic GVHD following immune modulation with immunosuppression withdrawal or donor lymphocyte infusion (DLI).
• Any clinical Manifestation consistent with de novo chronic GVHD or overlapped syndrome of acute and chronic GVHD.
• Patients who are unable to tolerate the volume shifts associated with ECP treatment due to the presence of any of the following conditions: uncompensated congestive heart failure, pulmonary edema, severe asthma or chronic obstructive pulmonary disease, hepatorenal syndrome.
• Active bleeding
• International normalized ration (INR) \>2
• Patients cannot have received methylprednisolone \> 2mg/kg/day for more than 72 hours prior to registration.
• Patients cannot have received any other immunosuppression for treatment of GVHD but calcineurin inhibitors and corticosteroids. Patients are allowed to have had any GVHD prophylaxis with the exception of ECP
• Patients with known hypersensitivity or allergy to psoralen
• Patients with known hypersensitivity or allergy to both citrate and heparin
• Patients with co-existing photosensitive disease (e.g. porphyria, systemic lupus erythematosus, albinism) or coagulation disorders.
• Uncontrolled, persistent hypertriglyceridemia, with levels \> 800 mg%

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Mallinckrodt: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Photopheresis; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

PUVA Therapy; Ultraviolet Therapy; Phototherapy; Therapeutics; Extracorporeal Circulation; Surgical Procedures, Operative; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Amin Majid Alousi, Associate Professor, Stem Cell Transplantation
• Organization: The University of Texas (UT) MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

713-792-7734

Study Officials

• Amin Alousi, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2008
• First Posted: February 7, 2008
• Study Start: January 1, 2008
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: June 4, 2018
• Results First Posted: June 4, 2018

Record last verified: 2018-05

Locations

US (1)