Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Active	18 to 85	NHLBI	070091 07-H-0091, NCT00433745

Trial Description

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.

Further Study Information

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).

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 CML).

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.

Trial Contact Information

Trial Lead Organizations/Sponsors

National Heart, Lung, and Blood Institute

Patient Recruitment and Public Liaison Office		Ph: (800) 411-1222
		Email: prpl@mail.cc.nih.gov

TTY

Ph: 1-866-411-1010

U.S.A.
Maryland
	Bethesda
	NCI - Center for Cancer Research

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00433745
Information obtained from ClinicalTrials.gov on March 18, 2009