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WTI Peptide Vaccination for Patients With High Risk Hematological Malignancies


Phase 2
18 Years
85 Years
Not Enrolling
Both
Myelodysplastic Syndrome, Acute Myeloid Leukemia (AML), Chronic Myeloid Leukemia (CML)

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Trial Information

WTI Peptide Vaccination for Patients With High Risk Hematological Malignancies


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. WT1 was identified as a target vaccine antigen because this antigen is
over-expressed by CD34 plus stem cells of most patients with myeloid and lymphoid
malignancies but not by normal marrow cells. An HLA-A0201 restricted peptide derived from
the 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 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).

Inclusion 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 lymphoablative 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 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 BMT treatment unlikely and making informed consent impossible.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:

12 weeks after last dose of vaccine

Safety Issue:

Yes

Authority:

United States: Federal Government

Study ID:

070091

NCT ID:

NCT00433745

Start Date:

February 2007

Completion Date:

November 2009

Related Keywords:

  • Myelodysplastic Syndrome
  • Acute Myeloid Leukemia (AML)
  • Chronic Myeloid Leukemia (CML)
  • 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
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Myelodysplastic Syndromes
  • Preleukemia
  • Hematologic Neoplasms

Name

Location

National Cancer Institute (NCI), 9000 Rockville PikeBethesda, Maryland  20892