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

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00923910
• Collaborator: (none)
• Enrollment: 10
• Location: 1
• Arms: 2
• Actual Duration (Months): 104.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia, Acute Myelogenous (AML); Leukemia, Acute Lymphocytic (ALL); Leukemia, Chronic Myelogenous (CML); Myelodysplastic Syndrome (MDS); Non-Hodgkin's Lymphoma (NHL)	Drug: WT1 Peptide-Pulsed Dendritic Cells; Drug: Donor Lymphocytes; Drug: IL-4; Drug: KLH; Drug: WT1 Peptides; Drug: Endotoxin; Drug: Diphenhydramine; Drug: Acetaminophen	Phase 1/Phase 2

Detailed Description

Background:

• Efforts to incorporate anti-tumor immunotherapy at stages of minimal residual disease (MRD) burden are limited by profound host immune depletion associated with standard anti-cancer therapies.

• Allogeneic blood and marrow stem cell transplantation (SCT) can be curative for a number of hematologic malignancies. Part of the success of this approach is an allogeneic immunologic reaction that has been demonstrated to play a role in the eradication of residual malignant disease after transplant in certain cancers (the so called graft-versus-leukemia, GVL, or graft-versus-tumor, GVT, effect). Nonetheless, relapse remains the primary cause of treatment failure after allogeneic SCT.

• The Wilm's tumor 1 (WT1) gene product is a tumor-associated antigen that represents a potential target for immunotherapy in a wide array of cancers. WT1 is expressed in most cases of acute leukemia and in many cases of chronic myelogenous leukemia and myelodysplastic syndromes. Importantly, WT1 has limited expression in normal tissues beyond embryogenesis. This trial represents an attempt to incorporate antigen-specific immunotherapy in the setting of allogeneic adoptive cell transfer.

Objectives:

• To determine the safety, toxicity, and feasibility of donor-derived dendritic cell vaccination and donor lymphocyte infusion (DLI) after allogeneic SCT.

• To determine the frequency and severity of graft-vs.-host disease (GVHD) in patients treated with peptide-loaded donor-derived dendritic cell vaccination and donor lymphocyte infusion (DLI).

• To evaluate whether immunologic responses to WT1-specific peptides can be generated by peptide-loaded donor-derived dendritic cell vaccination and DLI after allogeneic SCT.

• To evaluate whether clinical responses to WT1-specific peptides can be generated by peptide-loaded donor-derived dendritic cell vaccination and DLI after allogeneic SCT.

• To evaluate whether immunologic and/or clinical responses may be associated with the degree of WT1 expression by malignant cells or pre-existing donor anti-WT1 immunity.

Eligibility:

• HLA-A2 plus patients may be enrolled on this trial if they have relapsed or residual disease following allogeneic SCT for a WT1 expressing hematologic malignancy.

• Donors from the previous SCT, related or unrelated, must be 5- or 6- antigen genotypic HLA-matched (single HLA-A or B locus mismatch allowed) and HLAA2 plus.

Design:

• This is a pilot study, the primary aim of which is to assess safety and feasibility of this novel vaccine strategy aimed to enhance the GVL effect after allogeneic SCT.

• Donor-derived dendritic cells prepared from peripheral blood monocytes will be loaded with a combination of three WT1-derived peptides. These peptides are each comprised of one WT1-derived oligomeric epitope known to bind to HLA-A2 and an 11-mer protein transduction epitope known to enhance peptide loading and antigen presentation.

• Patients will receive donor-derived dendritic cell vaccines every 14 days for 6 doses. Donor leukocyte infusions (DLI) will also be administered with the vaccine.

• Study endpoints will include toxicity, feasibility, antigen-specific immunity, and disease response.

• This is an exploratory pilot trial. Up to 12 patients will be treated.

• Stopping rules will take effect if excessive toxicity (e.g., GVHD) or inability to generate vaccines are observed.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Trial of WT1 Peptide-Loaded Allogeneic Dendritic Cell Vaccine and Donor Lymphocyte Infusion for WT1-Expressing Hematologic Malignancies
• Actual Study Start Date: Feb 22, 2008
• Actual Primary Completion Date: Oct 18, 2013
• Actual Study Completion Date: Nov 15, 2016

Arms and Interventions

Arm	Intervention/Treatment
Other: Donors Related and unrelated donors undergo lymphapheresis to prepare cellular vaccines and to donate lymphocytes for infusion.	Drug: Donor Lymphocytes; Lymphocytes from donors (related or unrelated) collected via lymphapheresis.; Drug: Diphenhydramine; Pre-medication; Other Names: Benadryl ; Drug: Acetaminophen; Pre-medication; Other Names: Tylenol
Experimental: Recipients Participants receive donor lymphocytes and vaccines prepared from donors.	Drug: WT1 Peptide-Pulsed Dendritic Cells; Other Names: Wilm's Tumor 1 ; Drug: Donor Lymphocytes; Lymphocytes from donors (related or unrelated) collected via lymphapheresis.; Drug: IL-4; water-soluble protein; this study will use GMCSF (granulocyte macrophage colony stimulating factor)/IL-4 generated monocyte derived dendritic cells; Other Names: Interleukin-4 ; Drug: KLH; Neoantigen known to induce helper responses; will be used concurrently as a vaccine adjuvant and control antigen.; Other Names: keyhole limpet hemocyanin ; Drug: WT1 Peptides; dendritic cell vaccine; Drug: Endotoxin; Purified lipopolysaccharide prepared from E.Coli 0:113; Drug: Diphenhydramine; Pre-medication; Other Names: Benadryl ; Drug: Acetaminophen; Pre-medication; Other Names: Tylenol

Outcome Measures

Primary Outcome Measures

1. Toxicity [21 months]

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

2. Number of Participants With Graft Versus Host Disease (GVHD) Greater Than or Equal to Grade 3 [28 days following completion of last vaccine and/or DLI (donor lymphocyte infusion) administration]

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

Secondary Outcome Measures

1. Time to Immune Response [4 to 12 weeks]

   Immune response was monitored by use of interferon gamma Enzyme-Linked Immunospot (ELISpot) and by delayed-type hypersensitivity (DTH) testing.

2. Wilm's Tumor 1 (WT1) Enzyme-Linked Immunospot (ELISpot) [48 to 72 hours after placement]

   WT1 expression of the hematologic malignancy was confirmed by either having greater than 15% of malignant cells react with anti-WT1 by immunohistochemistry or by having a positive quantitative reverse transcription polymerase chain reaction (RT-PCR) of WT1 compared with a negative control.

3. Wilm's Tumor (WT1) Delayed-type Hypersensitivity (DTH) [48 to 72 hours after placement]

   WT1 expression of the hematologic malignancy was confirmed by either having greater than 15% of malignant cells react with anti-WT1 by immunohistochemistry or by having a positive quantitative reverse transcription polymerase chain reaction (RT-PCR) of WT1 compared with a negative control. DTH skin testing was performed using KLH and with a cocktail of WT1 peptides as 2 separate injections. Enzyme-Linked Immunospot (ELISpot) was performed against each peptide and was considered positive if results were at least 10 spots above background on at least 2 measurements. DTH was considered positive if there was at least .5cm induration 48 to 72 hours after placement.

4. Keyhole Limpet Hemocyanin (KLH) Delayed-type Hypersensitivity (DTH) [48 to 72 hours after placement]

   KLH is a neoantigen known to induce helper response was used concurrently as a vaccine adjuvant and control antigen. DTH skin testing was performed using KLH and with a cocktail of WT1 peptides as 2 separate injections. Enzyme-Linked Immunospot (ELISpot) was performed against each peptide and was considered positive if results were at least 10 spots above background on at least 2 measurements. DTH was considered positive if there was at least .5cm induration 48 to 72 hours after placement.

5. Number of Participants With Progressive Disease [4 to12 weeks]

   Progressive disease is at least a 20% increase in the sum of the longest diameter of all target lesions (i.e. tumor response). Response criteria for acute leukemia's is worse marrow classification (i.e., M status) with at least a 50% increase in the percentage of marrow blasts, or no change in marrow classification (i.e., M status), but a 50% or greater increase in absolute peripheral blast count or extent of medullary disease

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Year to 74 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

• INCLUSION CRITERIA:

Inclusion Criteria: Patient (i.e., transplant recipient)

Age greater than 1 year and less than 75 years.

One of the following Wilm's Tumor 1 (WT1)-expressing hematologic malignancies:

1. Acute lymphocytic leukemia (ALL), less than or equal to 25 percent marrow blasts.

2. Acute myelogenous leukemia (AML), less than or equal to 25 percent marrow blasts.

3. 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

1. Myelodysplastic syndrome (MDS), less than 20 percent marrow blasts.

2. Non-Hodgkin's lymphoma (NHL), stage 4, less than or equal to 25 percent marrow blasts.

3. Hodgkin's lymphoma (HL)

4. There will be no restriction on the volume of extramedullary disease, with the exceptions of exclusions for central nervous system involvement or progression deemed unacceptably rapid.

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).

Prior stem cell transplantation (SCT): Prior HLA-matched (5-6/6 antigen or 8-10/10 allele) related or unrelated allogeneic SCT required. Must be at least 42 days post-transplant, have had recovery of transplant-associated toxicity to less than grade 2, and have post-transplant donor engraftment as defined by donor chimerism greater than 50 percent (peripheral blood), neutrophil recovery to an absolute neutrophil count (ANC) greater than 500/microl independent of myeloid growth factors, and platelet recovery to greater than 20,000/microL independent of transfusion.

Disease status: Post-transplant residual or relapsed disease. Minimal residual disease (MRD) by polymerase chain reaction (PCR) or flow cytometry is acceptable in accordance with standard disease-specific diagnostic criteria.

Availability of previous allogeneic donor to donate cells again.

Prior therapy: Disease-specific therapy must be stopped at least 14 days prior to protocol Cycle 1 Day 1 (C1D1) and recovery of treatment-associated toxicity to greater than grade 2 is required prior to initiation of protocol therapy. Patients may have received prior DLI, but the last dose must be at least 28 days prior to C1D1 and there must be no active graft versus host disease (GVHD) greater than grade 1 acute or extensive chronic. Systemic immunosuppression must be stopped at least 28 days prior to protocol C1D1 and there must be no active GVHD greater than grade 1 acute or extensive chronic. There is no time restriction in regard to prior intrathecal chemotherapy provided there is complete recovery from any acute toxic effects of such. Patients receiving hydroxyurea are allowed.

Performance status of 0, 1, 2, or 3.

Renal function: Patients must have a serum creatinine less than or equal to 1.5 times the upper limit of normal based on age-specific normal range OR a creatinine clearance greater than or equal to 60 mL/min/1.73 m^2.

Hepatic function: Patients must have a total bilirubin less than or equal to 2.0 mg/dl and alanine aminotransferase (ALT) less than or equal to 5 times the upper limit of normal based on age- specific normal ranges.

Ability to give informed consent. For patients less than 18 years of age, their legal guardian must give informed consent. Pediatric patients will be included in age appropriate discussion in order to obtain verbal assent.

Recipients of unrelated donor transplants must sign a release of information form to authorize National Marrow Donor Program (NMDP) transfer of information to the National Institutes of Health (NIH).

Subjects of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while they are being treated on this study.

Inclusion Criteria: Donor

Weight greater than or equal to 18 kg, and for unrelated donors only age greater than or equal to 18 years

Previous HLA-matched related or unrelated allogeneic donor. Donors must be 5-6/6 antigen or 8-10/10 allele matched.

HLA-A2 plus (heterozygous expression is acceptable).

Adequate venous access for peripheral apheresis, or consent to use a temporary central venous catheter for apheresis.

Donor selection will be in accordance with National Institutes of Health (NIH)/Clinical Center (CC) Department of Transfusion Medicine (DTM) criteria and, in the case of an unrelated donor, the National Marrow Donor Program (NMDP) standards. When a potentially eligible recipient of an unrelated donor product is identified, the recipient will complete an NMDP search transfer request to allow NIH NMDP staff to contact the NMDP Coordinating Center, who will, in turn, contact the donor's prior Donor Center. The NMDP Policy for Subsequent Donation Requests will be followed and the appropriate forms (Subsequent Donation Request form and Therapeutic T Cell Collection Prescription) will be submitted as required.

Ability to give informed consent. For donors less than 18 years of age, their legal guardian must give informed consent. Pediatric donors must give verbal assent and be cleared by social work and a mental health specialist to participate.

EXCLUSION CRITERIA:

Exclusion Criteria: Patient

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.

• Neuroblastoma (NB): History of CNS involvement without current evidence of CNS malignancy is NOT an exclusion.

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.

Exclusion Criteria: Donor

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.

Positive screening test for transfusion-transmissible infection in accordance with DTM or NMDP donation standards.

Kaposi's sarcoma

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland	United States	20892

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Terry J Fry, M.D., National Cancer Institute (NCI)

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• NIH Clinical Center Detailed Web Page

Publications

• Appelbaum FR. Graft versus leukemia (GVL) in the therapy of acute lymphoblastic leukemia (ALL). Leukemia. 1997 May;11 Suppl 4:S15-7. Review.
• 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. Erratum in: Blood 1989 Aug 15;74(3):1180.
• Witz JP, Roeslin N, Avalos S, Morand G, Wihlm JM. [Benign tracheo-bronchial tumors. Other tumors]. Ann Chir. 1979 Oct;33(8):541-4. French.

• Responsible Party: Terry Fry, M.D., Principal Investigator, National Institutes of Health Clinical Center (CC)
• ClinicalTrials.gov Identifier: NCT00923910
• Other Study ID Numbers: 080051; 08-C-0051; NCT00608166
• First Posted: Jun 18, 2009
• Last Update Posted: Apr 12, 2017
• Last Verified: Mar 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Terry Fry, M.D., Principal Investigator, National Institutes of Health Clinical Center (CC): 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
• Additional relevant MeSH terms: Lymphoma; Leukemia; Preleukemia; Lymphoma, Non-Hodgkin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Acute Disease; Acetaminophen; Diphenhydramine; Promethazine; Interleukin-4; Keyhole-limpet hemocyanin

Study Results

Participant Flow

Arm/Group Title	Donors	Recipients
Arm/Group Description	Period 1 -Donor lymphocyte collection via apheresis. Period 2 -Donor cell processing for vaccine and infusion.	Period 1 - Vaccine and donor lymphocyte prep Period 2 - Vaccine and donor lymphocyte administration.
Period Title: Period 1
STARTED	5	5
COMPLETED	5	5
NOT COMPLETED	0	0
Period Title: Period 1
STARTED	5	5
COMPLETED	5	5
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Donors	Recipients	Total
Arm/Group Description	Donor lymphocyte collection via apheresis.	Vaccine and donor lymphocyte prep	Total of all reporting groups
Overall Participants	5	5	10
Age (Count of Participants)
<=18 years	1 20%	3 60%	4 40%
Between 18 and 65 years	4 80%	2 40%	6 60%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Median (Standard Deviation) ]
Median (Standard Deviation) [years]	21 (9.17)	17 (3.71)	19 (8.72)
Sex: Female, Male (Count of Participants)
Female	1 20%	2 40%	3 30%
Male	4 80%	3 60%	7 70%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 20%	1 20%	2 20%
Not Hispanic or Latino	4 80%	4 80%	8 80%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	5 100%	5 100%	10 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	5 100%	5 100%	10 100%
Disease (participants) [Number]
Hodgkin	1 20%	1 20%
ALL	3 60%	3 60%
AML	1 20%	1 20%
Transplantation Type (participants) [Number]
NMA	2 40%	2 40%
MA	2 40%	2 40%
MA x 2	1 20%	1 20%
Donors (participants) [Number]
MSD	3 60%	3 60%
MRD*	1 20%	1 20%
MUD	1 20%	1 20%
Conditioning Regimen (participants) [Number]
Fludarabine/cyclophosphamide	2 40%	2 40%
Cyclophosphamide, TBI, thiotepa	1 20%	1 20%
HSCT1:cyclo,TBI;HSCT2:busulfan, melphalan, etop	1 20%	1 20%
Cyclophosphamide, TBI	1 20%	1 20%
Immunosuppression (participants) [Number]
Cyclosporine	3 60%	3 60%
Sirolimus/tacrolimus, methotrexate	1 20%	1 20%
None after second BMT	1 20%	1 20%
Time Off Immunosuppression before Protocol Enrollment (Months) [Number]
Patient 1	10	10
Patient 2	28	28
Patient 3	11	11
Patient 4	23	23
Patient 5	9	9
Pre-Enrollment Disease Status (participants) [Number]
6%-8% blasts	1 20%	1 20%
Multiple 1-2cm lymph nodes	1 20%	1 20%
5%-10% blasts	1 20%	1 20%
2% blasts	1 20%	1 20%
5% blasts	1 20%	1 20%
Time to HCT to Relapse, mo (Months) [Number]
Patient 1	8	8
Patient 2	1	1
Patient 3	12	12
Patient 4	11	11
Patient 5	12	12
Time to First Vaccine (from day 0 of HCT), mo (Months) [Number]
Patient 1	14	14
Patient 2	32	32
Patient 3	14	14
Patient 4	29	29
Patient 5	15	15

Outcome Measures

1. Primary Outcome

Title	Toxicity
Description	Here is the number of participants with adverse events. For details of the adverse events, see the adverse event module.
Time Frame	21 months

Outcome Measure Data

Analysis Population Description

Only recipients were monitored for adverse events.

Arm/Group Title	Recipients
Arm/Group Description	Vaccine and donor lymphocyte prep
Measure Participants	5
Number [participants]	5 100%

2. Primary Outcome

Title	Number of Participants With Graft Versus Host Disease (GVHD) Greater Than or Equal to Grade 3
Description	Acute Graft versus Host Disease (GVHD) was graded by the modified Glucksberg scale. 0 = no GVHD normal, 4 = severe GVHD.
Time Frame	28 days following completion of last vaccine and/or DLI (donor lymphocyte infusion) administration

Outcome Measure Data

Analysis Population Description

Data for the frequency and severity of GVHD was captured as an endpoint for this trial. The donor arm is not included here because they were not evaluated for this outcome measure; recipients only.

Arm/Group Title	Recipients
Arm/Group Description	Vaccine and donor lymphocyte prep
Measure Participants	5
Number [participants]	0 0%

3. Secondary Outcome

Title	Time to Immune Response
Description	Immune response was monitored by use of interferon gamma Enzyme-Linked Immunospot (ELISpot) and by delayed-type hypersensitivity (DTH) testing.
Time Frame	4 to 12 weeks

Outcome Measure Data

Analysis Population Description

The donor arm is not included here because they were not evaluated for this outcome measure; recipients only.

Arm/Group Title	Recipients
Arm/Group Description	Period 1 - Vaccine and donor lymphocyte prep Period 2 - Vaccine and donor lymphocyte administration.
Measure Participants	5
Patient 1	12
Patient 2	NA
Patient 3	8
Patient 4	4
Patient 5	3

4. Secondary Outcome

Title	Wilm's Tumor 1 (WT1) Enzyme-Linked Immunospot (ELISpot)
Description	WT1 expression of the hematologic malignancy was confirmed by either having greater than 15% of malignant cells react with anti-WT1 by immunohistochemistry or by having a positive quantitative reverse transcription polymerase chain reaction (RT-PCR) of WT1 compared with a negative control.
Time Frame	48 to 72 hours after placement

Outcome Measure Data

Analysis Population Description

The donor arm is not included here because they were not evaluated for this outcome measure; recipients only.

Arm/Group Title	Recipients
Arm/Group Description	Period 1 - Vaccine and donor lymphocyte prep Period 2 - Vaccine and donor lymphocyte administration.
Measure Participants	5
Positive	3 60%
Negative	2 40%

5. Secondary Outcome

Title	Wilm's Tumor (WT1) Delayed-type Hypersensitivity (DTH)
Description	WT1 expression of the hematologic malignancy was confirmed by either having greater than 15% of malignant cells react with anti-WT1 by immunohistochemistry or by having a positive quantitative reverse transcription polymerase chain reaction (RT-PCR) of WT1 compared with a negative control. DTH skin testing was performed using KLH and with a cocktail of WT1 peptides as 2 separate injections. Enzyme-Linked Immunospot (ELISpot) was performed against each peptide and was considered positive if results were at least 10 spots above background on at least 2 measurements. DTH was considered positive if there was at least .5cm induration 48 to 72 hours after placement.
Time Frame	48 to 72 hours after placement

Outcome Measure Data

Analysis Population Description

The donor arm is not included here because they were not evaluated for this outcome measure; recipients only.

Arm/Group Title	Recipients
Arm/Group Description	Period 1 - Vaccine and donor lymphocyte prep Period 2 - Vaccine and donor lymphocyte administration.
Measure Participants	5
Positive	2 40%
Negative	2 40%
NA (Not available)	1 20%

6. Secondary Outcome

Title	Keyhole Limpet Hemocyanin (KLH) Delayed-type Hypersensitivity (DTH)
Description	KLH is a neoantigen known to induce helper response was used concurrently as a vaccine adjuvant and control antigen. DTH skin testing was performed using KLH and with a cocktail of WT1 peptides as 2 separate injections. Enzyme-Linked Immunospot (ELISpot) was performed against each peptide and was considered positive if results were at least 10 spots above background on at least 2 measurements. DTH was considered positive if there was at least .5cm induration 48 to 72 hours after placement.
Time Frame	48 to 72 hours after placement

Outcome Measure Data

Analysis Population Description

The donor arm is not included here because they were not evaluated for this outcome measure; recipients only.

Arm/Group Title	Recipients
Arm/Group Description	Period 1 - Vaccine and donor lymphocyte prep Period 2 - Vaccine and donor lymphocyte administration.
Measure Participants	5
Positive	3 60%
Negative	1 20%
NA (Not available)	1 20%

7. Secondary Outcome

Title	Number of Participants With Progressive Disease
Description	Progressive disease is at least a 20% increase in the sum of the longest diameter of all target lesions (i.e. tumor response). Response criteria for acute leukemia's is worse marrow classification (i.e., M status) with at least a 50% increase in the percentage of marrow blasts, or no change in marrow classification (i.e., M status), but a 50% or greater increase in absolute peripheral blast count or extent of medullary disease
Time Frame	4 to12 weeks

Outcome Measure Data

Analysis Population Description

The donor arm is not included here because they were not evaluated for this outcome measure; recipients only.

Arm/Group Title	Recipients
Arm/Group Description	Period 1 - Vaccine and donor lymphocyte prep Period 2 - Vaccine and donor lymphocyte administration.
Measure Participants	5
Number [participants]	5 100%

Adverse Events

Time Frame	21 months
Adverse Event Reporting Description	Only recipients were monitored for adverse events.
Arm/Group Title	Recipients
Arm/Group Description	Vaccine and donor lymphocyte prep
All Cause Mortality
	Recipients
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Recipients
	Affected / at Risk (%)	# Events
Total	0/5 (0%)
Other (Not Including Serious) Adverse Events
	Recipients
	Affected / at Risk (%)	# Events
Total	5/5 (100%)
Blood and lymphatic system disorders
Coagulation - Other, Specify - PT, prolonged	1/5 (20%)	2
Iron overload	1/5 (20%)	1
Platelets-low	5/5 (100%)	30
Leukocytes (total WBC) - low	4/5 (80%)	26
PTT (partial thromboplastin time)	2/5 (40%)	2
Hemoglobin-low	4/5 (80%)	14
Neutrophils/granulocytes (ANC/AGC) - low	4/5 (80%)	21
Cardiac disorders
Hypotension	1/5 (20%)	2
Supraventricular and nodal arrhythmia: sinus bradycardia	1/5 (20%)	1
Supraventricular and nodal arrhythmia: sinus tachycardia	2/5 (40%)	2
Eye disorders
Dry eye syndrome	1/5 (20%)	1
Ocular/Visual - Other, Specify - Eye drainage	1/5 (20%)	1
Pain: Eye	1/5 (20%)	1
Vision-blurred vision	1/5 (20%)	1
Gastrointestinal disorders
Anorexia	1/5 (20%)	1
Esophagitis	1/5 (20%)	1
Nausea	2/5 (40%)	2
Pain: Abdomen NOS	3/5 (60%)	3
Diarrhea	2/5 (40%)	2
General disorders
Fatigue (asthenia, lethargy, malaise)	1/5 (20%)	1
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0x10e9/L)	3/5 (60%)	5
Insomnia	1/5 (20%)	1
Rigors/chills	1/5 (20%)	2
Sweating (diaphoresis)	1/5 (20%)	1
Pain:pain NOS	1/5 (20%)	3
Hepatobiliary disorders
Hepatobiliary/pancreas- Other, Specify - non-alcoholic Steatoheptits	1/5 (20%)	1
Immune system disorders
Allergy/Immunology - Other, Specify - allergy to Sorbaview	1/5 (20%)	1
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutriphils:lung (pneumonia)	1/5 (20%)	1
Febrile neutropenia	1/5 (20%)	1
Infection with unknown ANC:sinus	1/5 (20%)	2
Infection with normal ANC or Grade 1 or 2 neutrophils:lung (pneumonia)	1/5 (20%)	1
Infection with normal ANC or Grade 1 or 2 neutrophils: upper airway NOS	1/5 (20%)	1
Metabolism and nutrition disorders
AST, SGOT (serum glutamic oxaloacetic transaminase) - high	3/5 (60%)	6
Glucose (serum -high (hyperglycemia)	2/5 (40%)	25
Glucose, serum-low (hypoglycemia)	4/5 (80%)	7
GGT (gamma-Glutamyl transpeptidase)	1/5 (20%)	1
Bicarbonate, serum low	2/5 (40%)	2
Albumin, serum low (hypoalbuminemia)	2/5 (40%)	19
Magnesium, serum high (hypermagnesemia)	2/5 (40%)	3
Magnesium, serum low (hypomagnesemia)	2/5 (40%)	7
Triglyceride, serum high (hypertriglyceridemia)	1/5 (20%)	3
Uric acid, serum high (hyperuricemia)	1/5 (20%)	4
Potassium, serum-high (hyperkalemia)	1/5 (20%)	3
Phosphate, serum low (hypophosphatemia)	1/5 (20%)	3
ALT, SGPT (serum glutamic pyruvic transaminase) - high	3/5 (60%)	12
Bilirubin (hyperbilirubinemia)	1/5 (20%)	3
Calcium, serum-low (hypocalcemia)	2/5 (40%)	18
Cholesterol, serum-high (hypercholesteremia)	1/5 (20%)	1
Potassium, serum-low (hypokalemia)	2/5 (40%)	9
Proteinuria	1/5 (20%)	1
Sodium, serum-high (hypernatremia)	1/5 (20%)	1
Sodium, serum-low (hyponatremia)	3/5 (60%)	6
Musculoskeletal and connective tissue disorders
Pain:Joint	1/5 (20%)	1
Pain: neck	1/5 (20%)	1
Pain:muscle	1/5 (20%)	1
Nervous system disorders
Pain: Head/Headache	2/5 (40%)	3
Mood alteration:anxiety	2/5 (40%)	2
Renal and urinary disorders
Urinary frequency/urgency	1/5 (20%)	1
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	1/5 (20%)	1
Hemorrhage, pulmonary/upper respiratory: Nose	1/5 (20%)	1
Cough	2/5 (40%)	3
Pain: chest wall	1/5 (20%)	1
Pain: throat/pharynx/larynx	2/5 (40%)	3
Skin and subcutaneous tissue disorders
Bruising (in absence of Grade 3 or 4 thrombocytopenia)	1/5 (20%)	1
Rash/desquamation	4/5 (80%)	11
Striae	1/5 (20%)	1
Pruritis/itching	4/5 (80%)	7

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.