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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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Martha Arellano, Emory University
ClinicalTrials.gov Identifier:
NCT00548847
First received: October 22, 2007
Last updated: November 22, 2013
Last verified: November 2013

October 22, 2007
November 22, 2013
January 2007
May 2014   (final data collection date for primary outcome measure)
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 ]
To assess the efficacy of GM-CSF and pegylated interferon-alpha 2b when administered to patients with AML, ALL, blast phase CML, and MDS relapsed after allogeneic transplantation, defined as progression-free survival of > 33% at 3 months. [ Time Frame: 3 months ]
Complete list of historical versions of study NCT00548847 on ClinicalTrials.gov Archive Site
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 ]
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 ]
Not Provided
Not Provided
 
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
A Pilot Phase II Study of Immunotherapy for the Treatment of AML, ALL, BP CML, and MDS Relapsed After Allogeneic Transplantation

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.

This is a pilot phase I1 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.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Leukemia
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.
Other Names:
  • GM-CSF
  • Interferon-α-2b
Experimental: 1
Intervention: Drug: GM-CSF, Interferon-α-2b
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
15
June 2015
May 2014   (final data collection date for primary outcome measure)

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.
Both
1 Year and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00548847
IRB00002219, 2219
No
Martha Arellano, Emory University
Emory University
Not Provided
Principal Investigator: Martha Arellano, MD Emory University Winship Cancer Institute
Emory University
November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP