MDACC Study Summary 2005-0167 (Archived)

Study Summary
No. 2005-0167:.......Blood And Marrow Transplantation......Amin Alousi......Stem Cell Transplantation and Cellular Therapy

Study Summary Title



Study Summary Number:	2005-0167

Study Title:	Initial Systemic Treatment of Acute GVHD: A Phase II Randomized Trial Evaluating Etanercept, Mycophenolate Mofetil (MMF), Denileukin Diftitox (Ontak), and Pentostatin in Combination with Corticosteroids

Physician

New Patient Referral



Name:	Amin Alousi	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Stem Cell Transplantation and Cellular Therapy	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-792-8750 Contact us about clinical trials

General Information



Disease Group:	Blood And Marrow Transplantation	Supported By:	N/A

Phase of Study:	Phase II	Return Visit:	It is standard of care that all patients are seen in the ambulatory treatment center between 3 and 7 days a week for the first 100 days following transplant, which is when the study takes place.

Treatment Agents:	Enbrel Methylprednisolone Mycophenolate Mofetil Ontak Pentostatin	Home Care:	This will depend on the severity of GVHD in each particular patient, as well as to the response to therapy

Treatment Loc:	Independent Multicenter Arrangements

Estimated Length of Stay in Houston:	This will depend on the severity of GVHD in each particular patient, as well as to the response to therapy

Description/
Intervention:

The goal of this clinical research study is to compare the effectiveness of 4
new study drugs, each combined with either prednisone or methylprednisolone, as
treatment for severe graft-versus-host disease (GVHD). The 4 drugs being
tested are Enbrel (Etanercept), Cellcept (Mycophenoloate Mofetil, or MMF),
Ontak (Denileukin Diftitox), and Nipent (Pentostatin). The safety of these
drug combinations will also be studied.

Study Objectives / Outcomes

Primary Objective: The primary objective is to estimate the proportion of CR at Day 28 of therapy for newly diagnosed acute GVHD for each of these agents given in combination with corticosteroids.

Secondary Objectives: Secondary objectives are to determine: proportion of partial response (PR), mixed response and progression at Day 28; proportion of treatment failure (no response, progression, or mortality) by Day 14; the incidence of GVHD flares requiring increasing therapy before Day 90. In addition, the following endpoints will be examined: incidence of discontinuation of immune suppression without flare by Days 90, 180 and 270 post-therapy, incidence of chronic GVHD by 9 months, overall survival at 6 and 9 months post initiation of therapy, incidence of systemic infections within 3 months of initiation of therapy, incidence of EBV-associated lymphoma.

Study Status Information



Study Activation / Registration Date:	08/31/2005

IRB Review and Approval Date:	06/15/2005

Study Type:	Therapeutic

Recruitment Status:	Terminated

Projected Accrual:	180

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:

1) Prior allogeneic hematopoietic stem cell transplant using either bone marrow, peripheral blood stem cells or cord blood. Recipients of non-myeloablative transplants are also eligible.

2) De novo Grade B-D acute GVHD diagnosed within 48 hours of diagnosis. GVHD is defined as the presence of skin rash and/or persistent nausea, vomiting, and/or diarrhea and/or cholestasis as the clinical criteria of GVHD when present in the right clinical setting and not directly attributable to other etiologies , such as drug rash, enteric infection, or hepatotoxic syndromes. The patient must havehad no previous systemic immune suppressive theapy given for treatment of acute GVHD except for a maximum of 48 hours of prior corticosteroid therapy (>1 mg/kg/day methylprednisolone).

3) No previous immune suppressive therapy given for treatment of acute GVHD except for a maximum 48 hours of prior corticosteroid therapy >/= 1 mg/kg/day methylprednisolone.

4) Clinical status at enrollment to allow tapering of steroids to not less than 0.6 mg/kg/day methylprednisolone (0.75 mg/kg/day prednisone) at Day 28 of therapy.

5) Absolute neutrophil count (ANC) greater than 500/microL

6) Estimated creatinine clearance greater than 30 mL/minute. At our institution this will be calculated with the Cockroft-Gault equation

7) Written informed consent from patient, parent or guardian.

8) Documentation that the assent document and education materials have been provided to, and reviewed with, patients under the age of 18.

9) Greater than or equal to 6years of age at the time of enrollment.

10) 10. DLI (donor lymphocyte infusion) as part of the original transplant therapy plan.

Exclusion Criteria:

1) ONTAK, pentostatin, or etanercept given within 7 days of enrollment

2) Active uncontrolled infection

3) GVHD developing after an unscheduled donor lymphocyte infusion, not part of the original transplant therapy plan, given for treatment of persistent or recurrent malignancy after transplantation

4) Patients receiving methylprednisolone>0.5mg/kg/day (or 0.6 mg/kg/day prednisone) within 7 days of onset of acute GVHD. If steroid therapy has been administered for a non-GVHD related condition and tapered to < 0.5 mg/kg/day methylprednidolone (or 0.6mg/kg/day prednisone) for seven or more days prior to the onset of acute GVHD, the patient is eligible.

5) Patients unlikely to be available at the transplantation center on Day 28 and 56 of therapy.

6) A clinical syndrome resembling de novo chronic GVHD developing at any time after allotransplantation. See Chapter 2 of the BMT CTN Manual of Procedures for details of de novo clinical GVHD.

7) Other investigational therapeutics for GVHD within 30 days, including agents used for GVHD prophylaxis

8) Patients who are pregnant, breast feeding, or, if sexually active, unwilling to use effective birth control for the duration of the study.

9) Adults unable to provide informed consent

10) Patients with a history of intolerance to any of the study drugs.

11) Patients with isolated limited skin (stage I) as the sole manifestation of acute GVHD.

Links

Registration Number: NCT00474149
Study Information on Clinical Trials Registry (clinicaltrials.gov)