Peptide Vaccinations to Treat Patients With Low-Risk Myeloid Cancers
Information source: National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Myelodysplastic Syndrome (MDS); Acute Myeloid Leukemia (AML); Chronic Myeloid Leukemia (CML)
Intervention: WT1:126-134 (Biological); PR1:169-177 Peptide (Biological); GM-CSF (Sargramostim) (Drug); Montanide adjuvant (Biological)
Phase: Phase 2
Status: Completed
Sponsored by: National Heart, Lung, and Blood Institute (NHLBI) Official(s) and/or principal investigator(s): Minocher Battiwalla, MD, Principal Investigator, Affiliation: National Institutes of Health- NHLBI
Summary
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:
- History and physical exam, chest x-ray, blood tests and bone marrow aspirate and biopsy
before starting the vaccinations.
- Safety monitoring during vaccine administration (every other week for 10 weeks) with
blood tests and check of vital signs.
- Follow-up safety monitoring (weeks 12 and 16) with blood tests every visit, chest x-ray
at week 12 and bone marrow biopsy visit 16.
Clinical Details
Official title: Efficacy of Peptide (WT1) and Peptide(PRI) Vaccination for Patients With Low Risk Myeloid Malignancies
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Efficacy in Inducing or Boosting a Cellular Immune Response
Secondary outcome: Clinical Response
Detailed description:
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.
Eligibility
Minimum age: 18 Years.
Maximum age: 85 Years.
Gender(s): Both.
Criteria:
- INCLUSION CRITERIA:
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)
OR
Diagnosed with AML and in complete remission within 5 years of treatment with less than 5%
marrow blasts
OR
Diagnosed with CML in chronic phase
Unsuitable for stem cell transplantation (SCT) (age over sixty or unavailability of a
fully-matched donor)
or
made an informed decision not to undergo the transplant procedure
or
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
EXCLUSION CRITERIA:
- Hypoplastic MDS
- Relapsed AML
- CML in accelerated phase or blast crisis
- Hypocellular bone marrow (less than 20%)
- History of Wegener's granulomatosis
- Serologic antibody against proteinase-3 (ANCA positive)
- Previous allergic reaction to Montanide Adjuvant
- Positive test for HIV
- Treatment with systemic corticosteroids or immunosuppressants within 14 days prior to
study entry
- Co-morbidity of such severity that it would preclude the patient's ability to
tolerate protocol therapy
- Predicted survival less than 28 days
- Pregnant or breast feeding (All female patients must have a urine pregnancy test
within 1 week prior to vaccine administration)
- Unwilling to practice abstinence or effective contraception (men and women) during
the study period.
- Enrolled in another drug or vaccine clinical trial during the study period
- Inability to comprehend the investigational nature of the study and provide informed
consent
Locations and Contacts
National Institutes of Health Clinical Center, 9000 Rockville Pike, Bethesda, Maryland 20892, United States
Additional Information
NIH Clinical Center Detailed Web Page
Starting date: June 2007
Last updated: June 5, 2014
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