LeukemiaPhase 2NCT00548847
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 Phase 2 study testing GM-CSF and Interferon-α-2b in people with Leukemia, run by Emory University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 year and older
- Conditions the study is for
- Leukemia
- What is being tested?
- GM-CSF and Interferon-α-2b
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2007to Mar 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Emory University Winship Cancer Institute
Atlanta, Georgia, 30322
About this study
Official title: 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.
Read the 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.
- Conditions
- Leukemia
- Being tested
- GM-CSF, Interferon-α-2b
- Keywords
- Leukemia
- Medical subject headings
- Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GM-CSFBiological
Also called Sargramostim, Leukine, Rhu GM-CSF, NSC #617589
Dosing schedule: 250 mcg/m² subcutaneously Mon-Wed-Fri. Response assessed between 2 and 4 weeks. Duration on study is 3 months.
Interferon-α-2bBiological
Also called Interferon-alpha-2b, Intron A®, Pegylated Interferon-α-2b, Peg-Intron
Dosing schedule: 1.5 mcg/kg subcutaneously Monday weekly. Response assessed between 2 and 4 weeks. Duration on study is 3 months.
| Study group | Role | What they receive |
|---|---|---|
| GM-CSF, Interferon-α-2b | Experimental | Not described Receives: Biological: GM-CSF; Biological: Interferon-α-2b |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 months after cytokine treatment
Secondary outcomes (1)
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)
Measured: 6 months after cytokine treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2007 (estimated)
- Study startJan 2007
- Primary completionMar 2015
- Study completionMar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer
- Responsible party
- Principal investigator, Martha Arellano, Emory University
- Investigators
- Martha Arellano, MD, Principal investigator, Emory University Winship Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00548847
- Sponsor's protocol ID
- IRB00002219
- Other IDs
- WCI1228-06
- Status last verified
- Sep 2016
- First submitted
- 22 Oct 2007
- Last updated
- 26 Oct 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Phase II Study of Immunotherapy for the Treatment of AML, ALL, BP CML, and MDS Relapsed After Allogeneic Transplantation
- ClinicalTrials.gov ID
- NCT00548847
- Acronym / sponsor ID
- IRB00002219
- Conditions
- Leukemia
- Keywords
- Leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- Bayer
- Study start
- Jan 2007
- Primary completion
- Mar 2015 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 24 Oct 2007 (estimated)
- Results
- Posted 18 Aug 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| GM-CSF, Interferon-α-2b | Experimental | Biological: GM-CSF, Biological: Interferon-α-2b |
Who may qualify
- Ages
- 1 year and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (12 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GM-CSFAlso: Sargramostim, Leukine, Rhu GM-CSF, NSC #617589Dosing schedule: 250 mcg/m² subcutaneously Mon-Wed-Fri. Response assessed between 2 and 4 weeks. Duration on study is 3 months. | Biological | GM-CSF, Interferon-α-2b |
| Interferon-α-2bAlso: Interferon-alpha-2b, Intron A®, Pegylated Interferon-α-2b, Peg-IntronDosing schedule: 1.5 mcg/kg subcutaneously Monday weekly. Response assessed between 2 and 4 weeks. Duration on study is 3 months. | Biological | GM-CSF, Interferon-α-2b |
Primary outcome
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 after cytokine treatment
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.
1 secondary outcome
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 after cytokine treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martha Arellano, MD principal investigator
Emory University Winship Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GM-CSF and Interferon-α-2b in people with Leukemia, run by Emory University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Aug 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 after cytokine treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2016.