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Phase 2 N=10 Treatment

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

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

Enrolled (actual)
10
Serious AEs
0.0%
Results posted
May 2014
Primary outcome: Primary: Toxicity — 5 participants

Study Design & Population

Study type
Interventional
Phase
Phase 2
Interventions
WT1 Peptide-Pulsed Dendritic Cells (Drug); Donor Lymphocytes (Drug); IL-4 (Drug); KLH (Drug); WT1 Peptides (Drug); Endotoxin (Drug); Diphenhydramine (Drug); Acetaminophen (Drug)
Age
Pediatric, Adult, Older Adult · 1+ yrs
Sex
All
Sponsor
National Cancer Institute (NCI)
Primary completion
Oct 2013

Outcome Measures

OutcomeResultp-value
PRIMARY
Toxicity
5
PRIMARY
Number of Participants With Graft Versus Host Disease (GVHD) Greater Than or Equal to Grade 3
SECONDARY
Time to Immune Response
12; NA; 8; 4; 3
SECONDARY
Wilm's Tumor 1 (WT1) Enzyme-Linked Immunospot (ELISpot)
3; 2
SECONDARY
Wilm's Tumor (WT1) Delayed-type Hypersensitivity (DTH)
2; 2; 1
SECONDARY
Keyhole Limpet Hemocyanin (KLH) Delayed-type Hypersensitivity (DTH)
3; 1; 1
SECONDARY
Number of Participants With Progressive Disease
5

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.

Eligibility Criteria

  • 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:

  • 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)
  • 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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00923910). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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