Wilm's Tumor 1 Protein Vaccine to Treat Cancers of the Blood

NCT00923910 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 08005108-C-0051
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Background:

• Most patients with acute lymphoblastic leukemia (ALL) and many patients with acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML) and non-Hodgkin's lymphoma (NHL) have a protein called Wilm's Tumor 1 (WT1) in their cancer cells. This protein is thought to be able to influence the growth of these cancers.
• A vaccine made with the WT1 protein may boost the immune system to help fight these cancers in patients whose cancer cells contain the protein. Objectives:
• To determine the safety, effectiveness and side effects of giving the WT1 vaccine and donor white blood cells to patients with AML, ALL, CML or NHL who have previously received standard treatment and undergone stem cell transplantation.
• To determine the immune response to the WT1 vaccine and donor white blood cells in these patients and to determine if the response is related to the amount of WT1 protein in the patient's cancer cells. Eligibility:
• Patients between 1 and 75 years of age with the blood antigen human leukocyte antigen (HLA-A2) and the WT1 cancer protein who have persistent or recurrent blood cancers after stem cell transplantation.
• The prior stem cell transplant donor must be willing to provide additional cells, which will be used to prepare the cellular vaccines and for donor lymphocyte (white blood cell) infusions. Design:
• Patients are given the WT1 vaccine every 2 weeks for 6 weeks (weeks 0, 2, 4, 6, 8, 10). Each vaccination consists of two injections in the upper arm or thigh.
• On weeks 0, 4 and 8, patients also receive white blood cells from a donor to enhance the immune response. The cells are also given as a 15- to 30-minute infusion through a vein about 1 hour after the vaccine injection. Donor infusions are given only to patients with mild or no graft-vs-host disease resulting from their prior stem cell transplantation.
• Periodic physical examinations, blood and urine tests, scans to evaluate disease and other tests as needed are done for 12 months after enrollment in the study.

Conditions

Leukemia, Acute Myelogenous (AML); Leukemia, Acute Lymphocytic (ALL); Leukemia, Chronic Myelogenous (CML); Myelodysplastic Syndrome (MDS); Non-Hodgkin's Lymphoma (NHL)

Keywords

WT1 Peptide Dendritic Cell Vaccine; Hematologic Malignancies; Relapse After Allogeneic Stem Cell Transplantation; Donor Lymphocyte Infusions; WT1-Positive; Dendritic Cell Vaccine; Tumor Immunotherapy; Allogeneic Adoptive Immunotherapy; Hodgkins Lymphoma; Leukemia; Acute Myelogenous Leukemia; AML; Acute Lymphocytic Leukemia; ALL; Chronic Myelogenous Leukemia; CML; Myelodysplasia Syndrome; Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (2)

• Toxicity

  Here is the number of participants with adverse events. For details of the adverse events, see the adverse event module.

  21 months

• Number of Participants With Graft Versus Host Disease (GVHD) Greater Than or Equal to Grade 3

  Acute Graft versus Host Disease (GVHD) was graded by the modified Glucksberg scale. 0 = no GVHD normal, 4 = severe GVHD.

  28 days following completion of last vaccine and/or DLI (donor lymphocyte infusion) administration

Secondary Outcomes (5)

• Time to Immune Response

  4 to 12 weeks

• Wilm's Tumor 1 (WT1) Enzyme-Linked Immunospot (ELISpot)

  48 to 72 hours after placement

• Wilm's Tumor (WT1) Delayed-type Hypersensitivity (DTH)

  48 to 72 hours after placement

• Keyhole Limpet Hemocyanin (KLH) Delayed-type Hypersensitivity (DTH)

  48 to 72 hours after placement

• Number of Participants With Progressive Disease

  4 to12 weeks

Study Arms (2)

Donors

OTHER

Related and unrelated donors undergo lymphapheresis to prepare cellular vaccines and to donate lymphocytes for infusion.

Drug: Donor Lymphocytes; Drug: Diphenhydramine; Drug: Acetaminophen

Recipients

EXPERIMENTAL

Participants receive donor lymphocytes and vaccines prepared from donors.

Drug: WT1 Peptide-Pulsed Dendritic Cells; Drug: Donor Lymphocytes; Drug: IL-4; Drug: KLH; Drug: WT1 Peptides; Drug: Endotoxin; Drug: Diphenhydramine; Drug: Acetaminophen

Interventions

WT1 Peptide-Pulsed Dendritic Cells DRUG

Also known as: Wilm's Tumor 1

Recipients

Donor Lymphocytes DRUG

Lymphocytes from donors (related or unrelated) collected via lymphapheresis.

Donors; Recipients

IL-4 DRUG

water-soluble protein; this study will use GMCSF (granulocyte macrophage colony stimulating factor)/IL-4 generated monocyte derived dendritic cells

Also known as: Interleukin-4

Recipients

KLH DRUG

Neoantigen known to induce helper responses; will be used concurrently as a vaccine adjuvant and control antigen.

Also known as: keyhole limpet hemocyanin

Recipients

WT1 Peptides DRUG

dendritic cell vaccine

Recipients

Endotoxin DRUG

Purified lipopolysaccharide prepared from E.Coli 0:113

Recipients

Diphenhydramine DRUG

Pre-medication

Also known as: Benadryl

Donors; Recipients

Acetaminophen DRUG

Pre-medication

Also known as: Tylenol

Donors; Recipients

Eligibility Criteria

• Age: 1 Year - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age greater than 1 year and less than 75 years.
• One of the following Wilm's Tumor 1 (WT1)-expressing hematologic malignancies:
• Acute lymphocytic leukemia (ALL), less than or equal to 25 percent marrow blasts.
• Acute myelogenous leukemia (AML), less than or equal to 25 percent marrow blasts.
• Chronic myelogenous leukemia (CML).
• Chronic phase, recurrent after or resistant to donor lymphocyte infusion (DLI) or resistant to available abl kinase inhibitors
• Accelerated phase, less than 20 percent marrow blasts
• Blastic phase, less than or equal to 25 percent marrow blasts
• Myelodysplastic syndrome (MDS), less than 20 percent marrow blasts.
• Non-Hodgkin's lymphoma (NHL), stage 4, less than or equal to 25 percent marrow blasts.
• Hodgkin's lymphoma (HL)
• WT1 expression will be confirmed by at least one of the following criteria:
• Greater than 15 percent of malignant cells react with anti-WT1 by immunohistochemistry.
• Positive quantitative reverse transcription polymerase chain reaction (RT-PCR) of WT1 compared with a negative control.
• Human leukocyte antigen (HLA-A2) plus (heterozygous expression is acceptable).

You may not qualify if:

• Active graft versus host disease (GVHD) greater than grade 1 acute or extensive chronic.
• Breast feeding or pregnant females (due to risk to fetus or newborn).
• Central nervous system (CNS) malignancy by any of the following criteria:
• Demonstration of malignant cells in the cerebrospinal fluid (CSF) in patients with leukemia or MDS as manifested by CSF white blood cell (WBC) greater than 5/microL and confirmation of CSF blasts.
• Cranial neuropathies deemed secondary to the underlying malignancy.
• CNS mass lesions deemed secondary to the underlying malignancy.
• Rapidly progressive malignancy and/or clinically significant systemic illness (e.g., severe unstable infections or organ dysfunction) that in the judgment of the PI would likely compromise the patient's ability to tolerate this therapy or interfere with the study procedures, including but not limited to a life expectancy of less than 3 months.
• High risk of inability to comply with protocol requirements as determined by principal investigator, social work, and primary team.
• Human immunodeficiency virus (HIV) infection or human T-lymphotrophic virus type 1 (HTLV-1) infection (due to associated immune suppression and decreased likelihood of developing an immune response to the vaccine and increased risk of severe infection).
• Active hepatitis B or C infection as defined by seropositive for hepatitis B surface antigen (HbSAg) or hepatitis C and elevated liver transaminases.
• Corticosteroids (dexamethasone equivalent up to 0.1 mg/kg/day) will be permitted. Topical agents and/or inhaled corticosteroids are permitted.
• History of medical illness that in the estimation of the principal investigator (PI) or Department of Transfusion Medicine (DTM)/NMDP physician poses prohibitive risk to donation.
• Anemia (Hb less than 10 gm/dl) or thrombocytopenia (less than 100,000/microliter).
• Breast feeding or pregnant females (due to risk to fetus or newborn).
• High risk of inability to comply with protocol requirements as determined by the principal investigator and donor center team.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Appelbaum FR. Graft versus leukemia (GVL) in the therapy of acute lymphoblastic leukemia (ALL). Leukemia. 1997 May;11 Suppl 4:S15-7.

  PMID: 9179275 BACKGROUND

• Sullivan KM, Weiden PL, Storb R, Witherspoon RP, Fefer A, Fisher L, Buckner CD, Anasetti C, Appelbaum FR, Badger C, et al. Influence of acute and chronic graft-versus-host disease on relapse and survival after bone marrow transplantation from HLA-identical siblings as treatment of acute and chronic leukemia. Blood. 1989 May 1;73(6):1720-8.

  PMID: 2653460 BACKGROUND

• Witz JP, Roeslin N, Avalos S, Morand G, Wihlm JM. [Benign tracheo-bronchial tumors. Other tumors]. Ann Chir. 1979 Oct;33(8):541-4. No abstract available. French.

  PMID: 229756 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myelodysplastic Syndromes; Lymphoma, Non-Hodgkin; Hematologic Neoplasms; Hodgkin Disease; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Interleukin-4; keyhole-limpet hemocyanin; Endotoxins; Diphenhydramine; Acetaminophen

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms by Site; Leukemia, Lymphoid

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Bacterial Toxins; Toxins, Biological; Ethylamines; Amines; Organic Chemicals; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Acetanilides; Anilides; Amides; Aniline Compounds

Results Point of Contact

• Title: Dr. Terry Fry
• Organization: National Cancer Institute

fryt@mail.nih.gov

301-402-0215

Study Officials

• Terry J Fry, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 17, 2009
• First Posted: June 18, 2009
• Study Start: February 22, 2008
• Primary Completion: October 18, 2013
• Study Completion: November 15, 2016
• Last Updated: April 12, 2017
• Results First Posted: May 8, 2014

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)