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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

Primary Purpose

Leukemia

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

GM-CSF

Interferon-α-2b

About this trial

This is an interventional treatment trial for Leukemia focused on measuring Leukemia

Eligibility Criteria

1 Year - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 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.
Eastern Cooperative Oncology Group (ECOG) performance status < 2 for adults, and Lansky status 60% for children.
Liver functions tests (aspartate transaminase [AST]/alanine aminotransferase [ALT]/bilirubin) < 5x the upper limit of normal.
Creatinine < 3x the upper limit of normal.
Lack of active grade 2-4 acute graft-versus-host disease (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 human leukocyte antigen (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, 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.
Breast feeding, due to unknown risk to the infant.
Inability to give informed consent.
Children under 1 year of age.

Sites / Locations

Emory University Winship Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

GM-CSF, Interferon-α-2b

Arm Description

Outcomes

Primary Outcome Measures

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

Efficacy is defined as progression-free survival of > 33% at 3 months. This is based on our retrospective data on 10% 3 month survival for relapsed patients. Progression is defined an an increase in blasts in blood or marrow by 50% compared to baseline with at least 20% of all cells being blasts at the time of assessment.

Secondary Outcome Measures

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)

Full Information

NCT ID

NCT00548847

First Posted

October 22, 2007

Last Updated

September 18, 2016

Sponsor

Emory University

Collaborators

Bayer

1. Study Identification

Unique Protocol Identification Number

NCT00548847

Brief Title

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

Official Title

A Pilot Phase II Study of Immunotherapy for the Treatment of AML, ALL, BP CML, and MDS Relapsed After Allogeneic Transplantation

Study Type

Interventional

2. Study Status

Record Verification Date

September 2016

Overall Recruitment Status

Completed

Study Start Date

January 2007 (undefined)

Primary Completion Date

March 2015 (Actual)

Study Completion Date

March 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Emory University

Collaborators

Bayer

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Leukemia

Keywords

Leukemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

15 (Actual)

8. Arms, Groups, and Interventions

Arm Title

GM-CSF, Interferon-α-2b

Arm Type

Experimental

Intervention Type

Biological

Intervention Name(s)

GM-CSF

Other Intervention Name(s)

Sargramostim, Leukine, Rhu GM-CSF, NSC #617589

Intervention Description

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

Intervention Name(s)

Interferon-α-2b

Other Intervention Name(s)

Interferon-alpha-2b, Intron A®, Pegylated Interferon-α-2b, Peg-Intron, Peginterferon alfa-2b

Intervention Description

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

Primary Outcome Measure Information:

Title

Description

Time Frame

3 months after cytokine treatment

Secondary Outcome Measure Information:

Title

Time Frame

6 months after cytokine treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

1 Year

Accepts Healthy Volunteers

Eligibility 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 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. Eastern Cooperative Oncology Group (ECOG) performance status < 2 for adults, and Lansky status 60% for children. Liver functions tests (aspartate transaminase [AST]/alanine aminotransferase [ALT]/bilirubin) < 5x the upper limit of normal. Creatinine < 3x the upper limit of normal. Lack of active grade 2-4 acute graft-versus-host disease (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 human leukocyte antigen (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, 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. Breast feeding, due to unknown risk to the infant. Inability to give informed consent. Children under 1 year of age.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Martha Arellano, MD

Organizational Affiliation

Emory University Winship Cancer Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

Emory University Winship Cancer Institute

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30322

Country

United States

12. IPD Sharing Statement

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