Peptide Vaccinations to Treat Patients With Low-Risk Myeloid Cancers
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|ClinicalTrials.gov Identifier: NCT00488592|
Recruitment Status : Completed
First Posted : June 20, 2007
Results First Posted : July 9, 2014
Last Update Posted : July 9, 2014
|First Submitted Date ICMJE||June 19, 2007|
|First Posted Date ICMJE||June 20, 2007|
|Results First Submitted Date||April 30, 2013|
|Results First Posted Date||July 9, 2014|
|Last Update Posted Date||July 9, 2014|
|Study Start Date ICMJE||June 2007|
|Actual Primary Completion Date||April 2010 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Efficacy in Inducing or Boosting a Cellular Immune Response [ Time Frame: 16 weeks ]
A T-cell response was considered positive if the frequencies of interferon (IFN-γ+) cluster of differentiation (CD8+) T cells in peptide-stimulated peripheral bloody mono-nucleated cells (PBMCs) were 2-fold or more higher than the frequencies of interferon (IFN-γ+) CD8+ T cells in unstimulated PBMCs and if there was a minimum of 0.05% Interferon (IFNγ+) CD8+ T cells (after subtracting the frequencies of interferon (IFNγ+) CD8+ T cells in unstimulated PBMCs). A significant vaccine-induced CD8+ T-cell response was defined as the emergence of detectable PR1 or WT1-specific CD8+ T cells when the pre-study analysis found no response, or a 2-fold increase in frequencies when responses were present before vaccination.
|Original Primary Outcome Measures ICMJE
||To evaluate the efficacy and toxicity assoc w/6 doses of a comb of WT-1:126-134 and PR1:169-177 peptide vaccines in Montanide adjuvant administered concomitantly with GM-CSF (Sargramostim) in selected patients with myeloid malignancies (MD|
|Change History||Complete list of historical versions of study NCT00488592 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||Clinical Response [ Time Frame: 16 weeks ]
Hematological response status
|Original Secondary Outcome Measures ICMJE
||Include clinical evaluation of disease response by following hematological measurements (reduction in marrow blast cells, changes in blood counts), transfusion dependence, and time to disease progression and survival.|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Peptide Vaccinations to Treat Patients With Low-Risk Myeloid Cancers|
|Official Title ICMJE||Efficacy of Peptide (WT1) and Peptide(PRI) Vaccination for Patients With Low Risk Myeloid Malignancies|
This study will test the safety and effectiveness of two vaccines on slowing disease progression, improving blood counts, reducing the need for transfusions of blood and platelets, or achieving remission in patients with myelodysplastic syndrome (MDS, also known as myelodysplasia), acute myeloid leukemia (AML) or chronic myeloid leukemia (CML). The vaccines consist of peptides (parts of proteins) found in MDS, AML and CML stem cells, combined with a substance called "MontanideTM". They are administered with granulocyte- macrophage colony- stimulating factor (GM-CSF). The Montanide and the GM-CSF help the immune system respond to the vaccines.
People 18 years of age or older with MDS, AML or CML may be eligible for this study.
Participants receive six injections of the vaccines, one dose every other week for a total of 10 weeks. The injections are given in the upper arm, upper leg, or abdomen. A separate injection of GM-CSF is given in the same area as the vaccine injections. Subjects are observed for 2 hours after the first vaccination and at least 30 minutes after each subsequent vaccination for allergic reactions. In addition to the vaccination, subjects undergo the following:
Leukemias and the related disorders myelodysplastic syndrome and myeloproliferative diseases represent a wide group of bone marrow stem cell malignancies. Some patients can be cured with chemotherapy or by allogeneic stem cell transplantation. However standard treatment approaches are not effective for patients who become refractory to chemotherapy, those who relapse after transplantation and those with progressive disease. The management of such patients remains unsatisfactory and requires new treatment approaches other than chemotherapy.
The immunological graft-versus-leukemia (GVL) effect seen after allogeneic stem cell transplantation suggests that stimulating the patient's own T cell responses to MDS and leukemia with a vaccine might also retard disease progression and even achieve disease remissions. Peptide (WT1) and peptide (PR1) were identified as target antigens because both antigens are highly expressed by cluster of differentiation 34 (CD34) plus stem cells of most patients with myeloid malignancies but not by normal marrow cells. An immunotherapeutic approach to vaccinate against PR1 and WT1 antigens could induce T cell response against MDS and leukemic cells while sparing normal cells and by using a combination of two antigens the risk of disease escape by antigen down regulation should be further diminished. Indeed in a safety study of one dose of a combination of peptide (PRl) and (WT1) vaccination, we demonstrated that immunological response against one or both vaccines could be induced in all subjects who were vaccinated. This immunological response was associated with a transient reduction in the leukemia burden. Furthermore the vaccine combination was well tolerated.
Therefore we propose this Phase II trial, the third in a series of planned peptide vaccine research protocols, which will evaluate the safety and efficacy associated with an immunotherapy approach using two peptide vaccines, namely PR 1 : 169- 177 and WT-1: 126-1 34 in Montanide adjuvant, administered concomitantly with GM-CSF (Sargramostim), every 2 weeks for 10 weeks (6 doses WT1 plus 6 doses PRl plus GM-CSF) in select patients diagnosed with MDS, AML or CML. Subjects with immunological response to one or both peptide vaccines will have the option of receiving an additional 6 boosters of the WT-1:126-135 and PR1:169-177 peptide vaccines at 3 monthly intervals.
The primary objective will be to evaluate the efficacy and toxicity associated with 6 doses of a combination of WT-1: 126-134 and PRl: 169-177 peptide vaccines in Montanide adjuvant administered concomitantly with GMCSF (Sargramostim) in selected patients with myeloid malignancies (MDS, AML, CML).
The primary endpoint will be immune response (studying changes in the frequencies of circulating PR1 and WT1 specific T cells) which will serves as a surrogate for evaluating for the efficacy of the study.
Secondary Endpoints will include changes in marrow blast cells, blood counts, transfusion dependence, time to disease progression and survival.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 2|
|Study Design ICMJE||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Study Arms||Experimental: WTI: 126-134/ PRI
Subjects were given 6 doses of PR1:169-177 in "Montanide" adjuvant and 6 doses of WT1:126-134 in "Montanide" adjuvant at 2 weekly intervals. The peptides were injected in the deep subcutaneous tissue of the anterior abdominal wall, the thighs or the upper arms near the deltoid region. The sites of injection were rotated every 2 weeks. GM-CSF (Sargramostim) was co administered with each vaccine dose. Subjects with immunological response to one or both peptide vaccines had the option of receiving a maximum of 6 additional boosters of the WT-1:126-134 and PR1:169-177 peptide vaccines at 3 monthly intervals.
|Publications *||Rezvani K, Yong AS, Mielke S, Jafarpour B, Savani BN, Le RQ, Eniafe R, Musse L, Boss C, Kurlander R, Barrett AJ. Repeated PR1 and WT1 peptide vaccination in Montanide-adjuvant fails to induce sustained high-avidity, epitope-specific CD8+ T cells in myeloid malignancies. Haematologica. 2011 Mar;96(3):432-40. doi: 10.3324/haematol.2010.031674. Epub 2010 Dec 6.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Actual Enrollment ICMJE
|Original Enrollment ICMJE
|Actual Study Completion Date||April 2010|
|Actual Primary Completion Date||April 2010 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
Diagnosed with MDS (B subtypes Refractory anemia (RA), Refractory anemia with ring sideroblasts (RARS) -Low Risk) (MDS with 5q- must have failed lenalidomide or been ineligible to receive it)
Diagnosed with AML and in complete remission within 5 years of treatment with less than 5% marrow blasts
Diagnosed with CML in chronic phase
Unsuitable for stem cell transplantation (SCT) (age over sixty or unavailability of a fully-matched donor)
made an informed decision not to undergo the transplant procedure
are between 6 months 3 years following allogeneic SCT and fulfill the following criteria:
100% donor engraftment,
Less than 5% blasts in marrow
normal marrow cellularity
Human leukocyte antigen (HLA-A020 1) positive at one allele
Ages 18-85 years old
Off all lympho-ablative chemotherapeutic agents
|Ages||18 Years to 85 Years (Adult, Older Adult)|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00488592|
|Other Study ID Numbers ICMJE||070159
07-H-0159 ( Other Identifier: National Heart Lung and Blood Institute )
|Has Data Monitoring Committee||Yes|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||Minoo Battiwalla, M.D., National Heart, Lung, and Blood Institute (NHLBI)|
|Study Sponsor ICMJE||National Heart, Lung, and Blood Institute (NHLBI)|
|Collaborators ICMJE||Not Provided|
|PRS Account||National Institutes of Health Clinical Center (CC)|
|Verification Date||June 2014|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP