Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Active	Over 1	Other	2219 NCT00548847

Trial Description

Summary

The relapse of acute leukemia, MDS and blast phase CML after allogeneic transplantation affects approximately 1/3 to 1/2 of all transplant recipients and is the main cause of treatment failure. There is currently no effective standard treatment for this condition.

This study will test the activity and feasibility of using a regimen to boost the immune system in order to treat AML, ALL, blast phase CML, and MDS relapse after allogeneic transplantation.

Further Study Information

This is a pilot phase II open label study testing the activity and feasibility of utilizing a regimen to boost the immune system in order to treat AML, ALL, blast phase CML, and MDS relapse after allogeneic transplantation. The regimen is a step-wise use of withdrawal of immunosuppression, cytoreduction if needed, administration of GM-CSF and pegylated IFN α-2b to patients who relapsed after an allogeneic transplant and will assess efficacy.

Relapse is the major problem following allogeneic hematopoietic progenitor cell transplants. There is currently no standard way to treat leukemia that relapsed after transplant, and patients have a poor prognosis.

A retrospective analysis of patients treated at Emory showed that administration of GM-CSF and interferon-alpha-2b was well-tolerated and affected long-term remissions in a small number of relapsed patients (after allogeneic transplant). Pre-clinical and clinical data from ours and other centers showed that relapsed leukemic blasts have down-regulation of co-stimulatory molecules and a tendency to evade the immune system. Cytokines can up-regulate co-stimulatory molecules on leukemic blasts and have been shown to increase the cytotoxicity of T-cells. This effect may be beneficial as a graft vs. leukemia effect for patients with relapse after allogeneic transplant.

Eligibility Criteria

Inclusion Criteria:

1. Age > 1 year.

2. Patients who have received an allogeneic transplant to treat AML, ALL, MDS, or CML and have relapse or progression of their AML, ALL, MDS, or CML are eligible to participate in the study. Relapse is defined as: reappearance of leukemic blasts as determined by morphologic analysis of the blood or marrow, reappearance of a phenotypic population of leukemia blasts by flow cytometric analysis of the blood or marrow, reappearance of a chromosome abnormality which is associated with the original leukemia as determined by chromosomal or FISH testing (ex: a translocation between chromosomes 9 and 22 for CML), reappearance of the molecular marker which is associated with the original leukemia as determined by PCR (ex: BCR-ABL for CML or ALL).

• Patients who received allogeneic transplantation to treat AML, ALL, MDS, or CML with detectable disease, and did not achieve remission of their leukemia after transplant are eligible.

3. ECOG performance status < 2 for adults, and Lansky status 60% for children.

4. Liver functions tests (AST/ALT/bilirubin) < 5x the upper limit of normal.

5. Creatinine < 3x the upper limit of normal.

6. Lack of active grade 2-4 acute GVHD 3 weeks after discontinuation of immunosuppression.

7. Patients with limited stage and extensive stage chronic GVHD of mild severity (lichenoid changes), or requiring < prednisone 10 mg/m2 daily will be included.

8. Recipients of grafts procured from related and unrelated donors with any level of HLA-matching.

Exclusion Criteria:

1. Pregnant patients are excluded due to unknown risk to the unborn fetus with cytokines.

2. Allergy to components of interferon-alpha-2b or GM-CSF.

3. Current uncontrolled infection.

4. Current grade 2-4 acute GVHD or chronic extensive GVHD of moderate to severe nature, requiring treatment with more than 10 mg/m2 of prednisone daily.

5. Uncompensated heart failure, NYHA class III-IV:

• Class I: patients with no limitation of activities; they suffer no symptoms from ordinary activities;

• Class II: patients with slight, mild limitation of activity; they are comfortable with rest or with mild exertion;

• Class III: patients with marked limitation of activity; they are comfortable only at rest;

• Class IV: patients who should be at complete rest, confined to bed or chair; any physical activity brings on discomfort and symptoms occur at rest.

6. Breast feeding, due to unknown risk to the infant.

7. Inability to give informed consent.

8. Children under 1 year of age.

Trial Contact Information

Trial Lead Organizations/Sponsors

Winship Cancer Institute of Emory University

Martha Arellano, MD

Principal Investigator

Stephanie McMillan, RN		Ph: 404-778-5714
		Email: stephanie.mcmillan@emoryhealthcare.org

U.S.A.
Georgia
	Atlanta
	Winship Cancer Institute of Emory University
		Martha Arellano, MD	Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00548847
Information obtained from ClinicalTrials.gov on May 04, 2009