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CompletedNCT00433745Updated Jul 8, 2014Results posted

Wilm's Tumor 1 (WT1) Peptide Vaccine for High Risk Hematologic Malignancy

A Phase 2 interventional study of WT1 Peptide Vaccine in Myelodysplastic Syndrome, Acute Myeloid Leukemia (AML) and Chronic Myeloid Leukemia (CML), sponsored by National Heart, Lung, and Blood Institute (NHLBI). Completed at 1 site in United States. Open to participants aged 18 Years to 85 Years. Per ClinicalTrials.gov, last updated 2014-07-08.

Sponsored by National Heart, Lung, and Blood Institute (NHLBI) · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
4
Allocation
Not applicable
Ages
18 Years to 85 Years
Sex
All
01

Study summary

This study will determine the safety and effectiveness of an experimental vaccine in controlling the abnormal growth of cells in patients with myelodysplastic syndrome (MDS, also known as myelodysplasia), acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic myeloid leukemia (CML). It will test whether the vaccine can increase the number of immune cells responding to the cancer and thereby slow progression of the illness, improve blood counts, reduce the need for transfusions of blood and platelets, or even achieve a disease remission. The vaccine contains part of a protein that is produced in large amounts by cells of patients with these cancers and an added substance called Montanide that helps the immune system respond to the vaccine. Sargramostim, another substances that boosts the immune response, is also given.

Patients 18 to 85 years of age with MDS, AML, ALL or CML may be eligible for this study. Candidates are screened with a medical history, physical examination, blood tests, chest x-ray and bone marrow biopsy. Women of childbearing age also have a pregnancy test.

Participants undergo the following:

  • Chemotherapy entering the study.
  • Leukapheresis to collect large amounts of white blood cells for infusion before vaccine administration.
  • Participants may need placement of a central line (plastic tube, or catheter) in the upper part of the chest to be used for giving chemotherapy, blood or platelet transfusions, antibiotics and white blood cells, and for collecting blood samples.
  • Weekly vaccine injections for nine weeks, given in the upper arm, upper leg or abdomen.
  • Sargramostim injections following each vaccination.
  • Standard of care treatment for MDS, AML, ALL or CML, which may include blood or platelet transfusions, growth factors, and drugs to control underlying disease and potential side effects of the vaccine.
  • Weekly safety monitoring, including vital signs check, brief health assessment, blood tests and observation after the vaccination, on the day of each vaccination.
  • Follow-up evaluations with blood tests and chest x-ray 3 weeks after the last vaccine dose and with blood tests and bone marrow biopsy 7 weeks after the last vaccine dose.
Read the 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 hematological malignancies might also retard disease progression and even achieve disease remissions. Wilm's Tumor 1 (WT1) was identified as a target vaccine antigen because this antigen is over-expressed by cluster of differentiation 34 (CD34) plus stem cells of most patients with myeloid and lymphoid malignancies but not by normal marrow cells. A human leukocyte antigen (HLA-A0201) restricted peptide derived from the Wilm's Tumor (WT) protein is anticipated to induce T cell response against MDS and leukemic cells while sparing normal cells. Of note, about 40% of the population is HLA-A0201 positive.

Therefore we propose this Phase II trial, the second in a series of planned peptide vaccine research, which will evaluate the safety associated with an immunotherapy approach of lymphodepletion, lymphocyte infusion, and WT1 vaccination in select patients diagnosed with MDS, AML, ALL and CML. The WT1 vaccination will comprise of 9 doses of WT-1 peptide vaccines (in Montanide adjuvant) administered concomitantly with granulocyte macrophage- colony stimulating factor (GM-CSF) (Sargramostim).

The primary objectives will be to evaluate the efficacy and toxicity associated with the immunotherapy approach of lymphodepletion, lymphocyte infusion, and WT1 vaccination in selected patients with hematological malignancies.

Secondary objectives will include evaluation of disease response by following the numbers of WT1 expressing cells in blood, hematological measurements (reduction in marrow blast cells, changes in blood counts), transfusion dependence, and time to disease progression and survival.

The primary endpoint will be the side effects of treatment (toxicity and number of circulating WT1 specific T cells (efficacy ) measured through week 16 of the study (7 weeks after the last dose of vaccine).

02

Conditions studied

  • Myelodysplastic Syndrome
  • Acute Myeloid Leukemia (AML)
  • Chronic Myeloid Leukemia (CML)

Keywords

  • Myelodysplastic Syndrome (MDS)
  • Acute Myelogenous Leukemia (AML)
  • Chronic Myelogenous Leukemia (CML)
  • Acute Lymphoblastic Leukemia (ALL)
  • Wilm's Tumor-1 Peptide
  • Leukemia
  • Myelodysplastic Syndrome
  • MDS
  • Acute Myelogenous Leukemia
  • AML
  • Chronic Myelogenous Leukemia
  • CML
  • Acute Lymphoblastic Leukemia
  • ALL
03

In context

Myelodysplastic Syndromes

2,165 studies on the registry are indexed under Myelodysplastic Syndromes; 322 are open to participants now.

This study's enrollment of 4 is below the median of 39 across 1,771 interventional studies indexed under Myelodysplastic Syndromes.

Browse Myelodysplastic Syndromes studies →

Lead sponsor

National Heart, Lung, and Blood Institute (NHLBI) is the lead sponsor of 1,143 studies on the registry; 72 are open to participants now.

Of its 58 completed or terminated interventional studies of FDA-regulated products, 50 (86%) have results posted.

Browse National Heart, Lung, and Blood Institute (NHLBI) studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 85 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

  • INCLUSION CRITERIA:

    1. Diagnosed with

      refractory anemia with excess of blasts (MDS-RAEB).

      or

      refractory anemia with excess of blasts in transformation (MDS-RAEBt).

      or

      secondary acute myelogenous leukemia (AML).

      or

      relapsed or refractory acute or chronic myelogenous leukemias (AML).

      or

      relapsed or refractory chronic myelogenous leukemias (CML) with accelerated phase or blast crisis

      or

      relapsed or refractory acute lymphoblastic leukemia (high risk ALL).

      or

      acute lymphoblastic leukemia (ALL) in complete remission.

      or

      chronic myelomonocytic leukemia (CMML).

    2. Unsuitable for stem cell transplantation (age over sixty or unavailability of a fully-matched donor).

      or

      made an informed decision not to undergo the transplant procedure.

      or

      relapsed AML, CML, MDS or ALL post stem cell transplantation (SCT).

    3. HLA-A0201 positive.
    4. Ages 18 - 85 years.
    5. Off all lympho-ablative chemotherapeutic agents.
    6. All subjects (men and women) must agree to practice abstinence or effective contraception during the study period.

Inclusion Criteria Donor (for post transplant subjects without available donor lymphocyte infusion (DLI) cells):

  1. Related donor, HLA identical (6/6) with recipient.
  2. Age greater than or equal to 18 or less than or equal to 80 years old.
  3. Ability to comprehend the investigational nature of the study and provide informed consent.

EXCLUSION CRITERIA:

  1. HIV positive (HIV-infected patients are immune-compromised and it is unlikely that these patients will be capable of mounting an immune response to the vaccine).
  2. Treatment with systemic corticosteroids within 7 days prior to study entry.
  3. Low bone marrow reserves (less than 20 percent cellularity).
  4. Serum creatinine greater than 2.5mg/dl or serum bilirubin greater than 4mg/dl (patients receiving fludarabine).
  5. Co-morbidity of such severity that it would preclude the patient's ability to tolerate protocol therapy.
  6. Predicted survival less than 3 months.
  7. Previous allergic reaction to Montanide Adjuvant.
  8. Pregnant or breast feeding (Pregnant and breast-feeding women are excluded from study because the effects of vaccination are not known and may pose a risk to the developing fetus. All female patients will have a urine pregnancy test, and only those that test negative will be allowed on study).
  9. Enrolled in another vaccine clinical trial during the study period.
  10. Inability to comprehend the investigational nature of the study and provide informed consent.

Exclusion Criteria-Donor (any of the following):

  1. Pregnant or lactating.
  2. Unfit to receive filgrastim (G-CSF) and undergo apheresis (abnormal blood counts, history of stroke, uncontrolled hypertension).
  3. HIV positive.
  4. Severe psychiatric illness. Mental deficiency sufficiently severe as to make compliance with the bone marrow transplant (BMT) treatment unlikely and making informed consent impossible.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
4 participants (actual)

Study arms

  • Experimental
    WT1 Peptide Vaccine

    WT1 vaccination (9 doses of WT-1:126-134 peptide (in Montanide adjuvant) administered concomitantly with GM-CSF (Sargramostim)

    Drug: WT1 Peptide Vaccine

Interventions

  • DrugWT1 Peptide Vaccine

    WT1 vaccination (9 doses of WT-1:126-134 peptide (in Montanide adjuvant) administered concomitantly with GM-CSF (Sargramostim)

    Also known as: Wilm's tumor 1 vaccine

06

What researchers measure

Primary outcomes

  1. Cellular Immune Response

    Minimum criterion for a cellular immune response was defined as the emergence of detectable T cell frequency against Willm's tumor 1 (WT1) when the pre-study analysis found no response, or a twofold increase in T cell frequency at any post vaccination time point

    Time frame: 7 weeks after last dose of vaccine

Secondary outcomes

  1. Disease Response

    Clinical response of underlying malignancy to the vaccination

    Time frame: 7 weeks after last dose of vaccine

07

Results

Posted Jul 8, 2014
Limitations and caveats
Although there was one partial response at 7 weeks, this patient went on to relapse as well. Consequently, all 4 patients had rapid relapses despite vaccination. Accrual was stopped at 4.

Participant flow

Participant flow — Overall Study
MilestoneWT1 Peptide Vaccine
Started4
Completed4
Not completed0

Outcome measures

PrimaryCellular Immune Response

Minimum criterion for a cellular immune response was defined as the emergence of detectable T cell frequency against Willm's tumor 1 (WT1) when the pre-study analysis found no response, or a twofold increase in T cell frequency at any post vaccination time point

Time frame:
7 weeks after last dose of vaccine
Reported as:
Number · participants
Cellular Immune Response
participantsWT1 Peptide Vaccine
Cellular Immune Response4
SecondaryDisease Response

Clinical response of underlying malignancy to the vaccination

Time frame:
7 weeks after last dose of vaccine
Reported as:
Number · participants
Disease Response
participantsWT1 Peptide Vaccine
Complete response0
Partial response1
No response3

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
WT1 Peptide Vaccine—0/4 (0%)0/4 (0%)

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)WT1 Peptide Vaccine
<=18 years0
Between 18 and 65 years3
>=65 years1
Age, Continuous
Age, Continuous(years)WT1 Peptide Vaccine
Mean54 ± 18
Sex: Female, Male
Sex: Female, Male(Participants)WT1 Peptide Vaccine
Female3
Male1
Region of Enrollment
Region of Enrollment(participants)WT1 Peptide Vaccine
United States4
08

Study locations

1 site
  • National Cancer Institute (NCI), 9000 Rockville Pike
    Bethesda, Maryland 20892, United States
09

References and documents

Publications

  • Rezvani K, Yong AS, Mielke S, Savani BN, Musse L, Superata J, Jafarpour B, Boss C, Barrett AJ. Leukemia-associated antigen-specific T-cell responses following combined PR1 and WT1 peptide vaccination in patients with myeloid malignancies. Blood. 2008 Jan 1;111(1):236-42. doi: 10.1182/blood-2007-08-108241. Epub 2007 Sep 17. PubMed 17875804 ↗
  • Rezvani K, Yong AS, Mielke S, Savani BN, Jafarpour B, Eniafe R, Le RQ, Musse L, Boss C, Childs R, John Barrett A. Lymphodepletion is permissive to the development of spontaneous T-cell responses to the self-antigen PR1 early after allogeneic stem cell transplantation and in patients with acute myeloid leukemia undergoing WT1 peptide vaccination following chemotherapy. Cancer Immunol Immunother. 2012 Jul;61(7):1125-36. doi: 10.1007/s00262-011-1187-z. Epub 2011 Dec 24. PubMed 22198310 ↗
10

Timeline

Tracking since Sep 25, 2026
Not marked actual or estimatedDates not marked actual or estimated

The record gives a start of Feb 2007, a primary completion of Nov 2009 and a completion of Nov 2009. It does not say whether these dates are actual or estimated.

Results were first posted in Jul 2014, 4 years 8 months after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered
Feb 9, 2007
First posted
Feb 12, 2007
Start
Feb 2007
Primary completionActual
Nov 2009
CompletionActual
Nov 2009
Results first posted
Jul 8, 2014
Last update
Jul 8, 2014
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Jul 8, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00433745
Lead sponsor
National Heart, Lung, and Blood Institute (NHLBI)
Responsible party
Minoo Battiwalla, M.D. (Principal Investigator, National Heart, Lung, and Blood Institute (NHLBI)) — Principal investigator
First posted
Feb 12, 2007
Start date
Feb 2007
Primary completion
Nov 2009
Completion
Nov 2009
Results posted
Jul 8, 2014
Last update
Jul 8, 2014

Study contacts

John Barrett, MD
principal investigator · National Institutes of Health- NHLBI

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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