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

NCT ID: NCT00548847

Last Updated: 2016-10-26

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-01-31

Study Completion Date

2015-03-31

Brief Summary

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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.

Detailed Description

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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 granulocyte-macrophage colony-stimulating factor (GM-CSF) and pegylated interferon (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.

Conditions

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Leukemia

Keywords

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Leukemia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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GM-CSF, Interferon-α-2b

Group Type EXPERIMENTAL

GM-CSF

Intervention Type BIOLOGICAL

Dosing schedule: 250 mcg/m² subcutaneously Mon-Wed-Fri. Response assessed between 2 and 4 weeks. Duration on study is 3 months.

Interferon-α-2b

Intervention Type BIOLOGICAL

Dosing schedule: 1.5 mcg/kg subcutaneously Monday weekly. Response assessed between 2 and 4 weeks. Duration on study is 3 months.

Interventions

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GM-CSF

Dosing schedule: 250 mcg/m² subcutaneously Mon-Wed-Fri. Response assessed between 2 and 4 weeks. Duration on study is 3 months.

Intervention Type BIOLOGICAL

Interferon-α-2b

Dosing schedule: 1.5 mcg/kg subcutaneously Monday weekly. Response assessed between 2 and 4 weeks. Duration on study is 3 months.

Intervention Type BIOLOGICAL

Other Intervention Names

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Sargramostim Leukine Rhu GM-CSF NSC #617589 Interferon-alpha-2b Intron A® Pegylated Interferon-α-2b Peg-Intron Peginterferon alfa-2b

Eligibility Criteria

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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 fluorescence in situ hybridization (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 polymerase chain reaction (PCR) (ex: breakpoint cluster region \[BCR\]-Abelson murine leukemia \[ABL\] 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. Eastern Cooperative Oncology Group (ECOG) performance status \< 2 for adults, and Lansky status 60% for children.
4. Liver functions tests (aspartate transaminase \[AST\]/alanine aminotransferase \[ALT\]/bilirubin) \< 5x the upper limit of normal.
5. Creatinine \< 3x the upper limit of normal.
6. Lack of active grade 2-4 acute graft-versus-host disease (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 human leukocyte antigen (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, New York Heart Association (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.
Minimum Eligible Age

1 Year

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bayer

INDUSTRY

Sponsor Role collaborator

Emory University

OTHER

Sponsor Role lead

Responsible Party

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Martha Arellano

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Martha Arellano, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University Winship Cancer Institute

Locations

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Emory University Winship Cancer Institute

Atlanta, Georgia, United States

Site Status

Countries

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United States

Other Identifiers

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WCI1228-06

Identifier Type: OTHER

Identifier Source: secondary_id

IRB00002219

Identifier Type: -

Identifier Source: org_study_id