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

Primary Purpose

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

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

WT1 Peptide Vaccine

About this trial

This is an interventional treatment trial for Myelodysplastic Syndrome focused on measuring 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

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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):

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

EXCLUSION CRITERIA:

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).
Treatment with systemic corticosteroids within 7 days prior to study entry.
Low bone marrow reserves (less than 20 percent cellularity).
Serum creatinine greater than 2.5mg/dl or serum bilirubin greater than 4mg/dl (patients receiving fludarabine).
Co-morbidity of such severity that it would preclude the patient's ability to tolerate protocol therapy.
Predicted survival less than 3 months.
Previous allergic reaction to Montanide Adjuvant.
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).
Enrolled in another vaccine clinical trial during the study period.
Inability to comprehend the investigational nature of the study and provide informed consent.

Exclusion Criteria-Donor (any of the following):

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

Sites / Locations

National Cancer Institute (NCI), 9000 Rockville Pike

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

WT1 Peptide Vaccine

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Disease Response

Clinical response of underlying malignancy to the vaccination

Full Information

NCT ID

NCT00433745

First Posted

February 9, 2007

Last Updated

June 5, 2014

Sponsor

National Heart, Lung, and Blood Institute (NHLBI)

1. Study Identification

Unique Protocol Identification Number

NCT00433745

Brief Title

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

Official Title

Wilm's Tumor 1 (WT1) Peptide Vaccination for Patients With High Risk Hematological Malignancies

Study Type

Interventional

2. Study Status

Record Verification Date

June 2014

Overall Recruitment Status

Completed

Study Start Date

February 2007 (undefined)

Primary Completion Date

November 2009 (Actual)

Study Completion Date

November 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

4 (Actual)

8. Arms, Groups, and Interventions

Arm Title

WT1 Peptide Vaccine

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

WT1 Peptide Vaccine

Other Intervention Name(s)

Wilm's tumor 1 vaccine

Intervention Description

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

Primary Outcome Measure Information:

Title

Cellular Immune Response

Description

Time Frame

7 weeks after last dose of vaccine

Secondary Outcome Measure Information:

Title

Disease Response

Description

Clinical response of underlying malignancy to the vaccination

Time Frame

7 weeks after last dose of vaccine

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

INCLUSION CRITERIA: 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). 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). HLA-A0201 positive. Ages 18 - 85 years. Off all lympho-ablative chemotherapeutic agents. 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): Related donor, HLA identical (6/6) with recipient. Age greater than or equal to 18 or less than or equal to 80 years old. Ability to comprehend the investigational nature of the study and provide informed consent. EXCLUSION CRITERIA: 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). Treatment with systemic corticosteroids within 7 days prior to study entry. Low bone marrow reserves (less than 20 percent cellularity). Serum creatinine greater than 2.5mg/dl or serum bilirubin greater than 4mg/dl (patients receiving fludarabine). Co-morbidity of such severity that it would preclude the patient's ability to tolerate protocol therapy. Predicted survival less than 3 months. Previous allergic reaction to Montanide Adjuvant. 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). Enrolled in another vaccine clinical trial during the study period. Inability to comprehend the investigational nature of the study and provide informed consent. Exclusion Criteria-Donor (any of the following): Pregnant or lactating. Unfit to receive filgrastim (G-CSF) and undergo apheresis (abnormal blood counts, history of stroke, uncontrolled hypertension). HIV positive. Severe psychiatric illness. Mental deficiency sufficiently severe as to make compliance with the bone marrow transplant (BMT) treatment unlikely and making informed consent impossible.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

John Barrett, MD

Organizational Affiliation

National Institutes of Health- NHLBI

Official's Role

Principal Investigator

Facility Information:

Facility Name

National Cancer Institute (NCI), 9000 Rockville Pike

City

Bethesda

State/Province

Maryland

ZIP/Postal Code

20892

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

17875804

Citation

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.

Results Reference

background

PubMed Identifier

22198310

Citation

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.

Results Reference

derived

Links:

URL

http://clinicalstudies.info.nih.gov/detail/B_2007-H-0091.html

Description

NIH Clinical Center Detailed Web Page

Learn more about this trial

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

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