Immunotherapy for Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), Blast Phase Chronic Myelogenous Leukemia (BP CML), and Mydelodysplastic Syndrome (MDS) Relapse After Allogeneic Transplantation - Full Text View

Sponsored by:	Emory University
Information provided by:	Emory University
ClinicalTrials.gov Identifier:	NCT00548847

Purpose

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.

Condition	Intervention	Phase
Leukemia	Drug: GM-CSF, Interferon-α-2b	Phase II

MedlinePlus related topics: Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood

Drug Information available for: Sargramostim Granulocyte-macrophage colony-stimulating factor Interferons

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Single Group Assignment, Efficacy Study
Official Title:	A Pilot Phase II Study of Immunotherapy for the Treatment of AML, ALL, BP CML, and MDS Relapsed After Allogeneic Transplantation

Further study details as provided by Emory University:

Primary Outcome Measures:

To assess the efficacy of GM-CSF and pegylated interferon-alpha 2b when administered to patients with AML, ALL, blast phase CML, and MDS relapse after allogeneic transplantation, defined as progression-free survival of > 33% at 3 months [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To evaluate overall survival at 6 months; evaluate overall responses; perform lab experiments to test hypothesis that exposure to interferon-alpha and GM-CSF up-regulates co-stimulatory molecule expression on relapsed acute leukemia cells [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	15
Study Start Date:	June 2007
Estimated Study Completion Date:	June 2010
Estimated Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental	Drug: GM-CSF, Interferon-α-2b Dosing schedule: GM-CSF, 250 mcg/m2 Mon-Wed-Fri; Pegylated Interferon-α-2b 1.5 mcg/kg Monday weekly. Response assessed between 2 and 4 weeks. Duration on study is 3 months.

Detailed Description:

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

Ages Eligible for Study:	1 Year and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age > 1 year.
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.
ECOG performance status < 2 for adults, and Lansky status 60% for children.
Liver functions tests (AST/ALT/bilirubin) < 5x the upper limit of normal.
Creatinine < 3x the upper limit of normal.
Lack of active grade 2-4 acute GVHD 3 weeks after discontinuation of immunosuppression.
Patients with limited stage and extensive stage chronic GVHD of mild severity (lichenoid changes), or requiring < prednisone 10 mg/m2 daily will be included.
Recipients of grafts procured from related and unrelated donors with any level of HLA-matching.

Exclusion Criteria:

Pregnant patients are excluded due to unknown risk to the unborn fetus with cytokines.
Allergy to components of interferon-alpha-2b or GM-CSF.
Current uncontrolled infection.
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.
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.
Breast feeding, due to unknown risk to the infant.
Inability to give informed consent.
Children under 1 year of age.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00548847

Contacts

Contact: Stephanie McMillan, RN

404-778-5714

stephanie.mcmillan@emoryhealthcare.org

Locations

United States, Georgia
Emory University Winship Cancer Institute	Recruiting
Atlanta, Georgia, United States, 30322
Principal Investigator: Martha Arellano, MD

Sponsors and Collaborators

Emory University

Investigators

Principal Investigator:

Martha Arellano, MD

Emory University Winship Cancer Institute

More Information

Responsible Party:	Winship Cancer Institute ( Martha Arellano, MD )
Study ID Numbers:	2219
Study First Received:	October 22, 2007
Last Updated:	October 27, 2008
ClinicalTrials.gov Identifier:	NCT00548847
Health Authority:	United States: Institutional Review Board

Keywords provided by Emory University:

Leukemia

Study placed in the following topic categories:

Blast Crisis
Leukemia, Lymphoid
Immunoproliferative Disorders
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Chronic myelogenous leukemia
Hematologic Diseases
Interferons
Acute myelogenous leukemia
Myeloproliferative Disorders

Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia
Lymphatic Diseases
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Bone Marrow Diseases
Lymphoproliferative Disorders
Acute myelocytic leukemia
Lymphoma

Additional relevant MeSH terms:

Anti-Infective Agents
Neoplastic Processes
Neoplasms
Pathologic Processes
Neoplasms by Histologic Type
Immune System Diseases

Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Pharmacologic Actions
Cell Transformation, Neoplastic

ClinicalTrials.gov processed this record on January 15, 2009