Vaccine Therapy and Basiliximab in Treating Patients With Acute Myeloid Leukemia in Complete Remission

Study Overview
=================
Brief Summary
-----------------
This randomized phase I trial studies the side effects and best way to give vaccine therapy together with basiliximab in treating patients with acute myeloid leukemia (AML) in complete remission. Vaccines made from the WT1 peptide may help the body build an effective immune response to kill cancer cells. Montanide ISA 51 VG and poly-ICLC may enhance this response. Monoclonal antibodies, such as basiliximab, can block cancer growth in different ways. Some block the ability of cancer to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. It is not yet known whether WT1 126-134 peptide vaccine with Montanide ISA 51 VG is more effective than with poly-ICLC when given together with basiliximab in treating AML

Detailed Description
-----------------
PRIMARY OBJECTIVES: I. To examine the immunogenicity of WT1 peptide (WT1 126-134 peptide vaccine) emulsified in Montanide (Montanide ISA 51 VG) in elderly patients with AML. II. To determine whether toll-like receptor 3 (TLR3) agonist (poly-L-lysine and carboxymethyl cellulose [poly ICLC]) could be a potent immunologic adjuvant, and increases the frequencies of WT1-specific T cells following vaccination. III. To determine whether depletion of regulatory T cells occurs upon administration of the anti-cluster of differentiation (CD)25 monoclonal antibody Basiliximab, and whether this is associated with increased frequencies of WT1-specific T cells following vaccination. IV. To assess whether WT1 vaccination +/- TLR3 agonist (poly ICLC) combined with Basiliximab results in decreased levels of WT1 transcripts in peripheral blood cells compared to WT1 vaccination +/- TLR3 as measured by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). SECONDARY OBJECTIVES: I. To examine the safety and gain preliminary information on efficacy of WT1 peptide vaccination +/- TLR3 agonist (poly ICLC) combined with Basiliximab. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive WT1 126-134 peptide vaccine emulsified in Montanide ISA 51 VG subcutaneously (SC) on day 0 and then once every 2 weeks. ARM B: Patients receive WT1 126-134 peptide vaccine emulsified in poly-ICLC SC on day 0 and then once every 2 weeks. ARM C: Patients assigned to Arm C receive basiliximab intravenously (IV) over 30 minutes on day -7 and WT1 126-134 peptide vaccine as in Arm A or Arm B, whichever had a superior cellular immune response. In all arms, treatment continues for 12 weeks in the absence of disease progression or unacceptable toxicity. Patients may then receive 6 additional monthly vaccinations. After completion of study treatment, patients are followed up for up to 2 years.

Official Title
-----------------
Randomized Phase I Study Combining Suppression of T Regulatory Cells With WT1 Vaccine Therapy for AML Patients in Complete Remission

Conditions
-----------------
Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)

Intervention / Treatment
-----------------
* Biological: basiliximab
* Biological: WT1 126-134 peptide vaccine
* Drug: Montanide ISA 51 VG
* Drug: poly ICLC
* Other: laboratory biomarker analysis


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with Hematological malignancies, including AML, MDS, CML in blast phase and other conditions at the investigator's discretion. Bone marrow biopsy-confirmed CR or CRi, more than CR1 is allowed, such as CR2 or CR3. The enrollee is deemed not a candidate for stem cell transplant due to advanced age or co-morbidities; or the enrollee does not have donor available; or enrollee refuses stem cell transplant due to personal belief; or stem cell transplant is not current standard of care. Patients who are post stem cell transplant in CR or CRi are allowed if they are off immunosuppression,and not treated with systematic steroid for GVHD Karnofsky performance status index > or = 80% Written informed consent Absolute neutrophil count > or = 500/μl Platelet count >= 20,000/μl with transfusion Creatinine = or < 2 x upper limit of normal (ULN) Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvate transaminase (SGPT) = or < 5 x ULN Bilirubin = or < 3 x ULN Human leukocyte antigens (HLA) typing: patient must express HLA-A2 Age > 18 years and < 85 years Electrocardiogram (EKG) without evidence of arrhythmia or changes that indicate acute ischemia Pulse oximetry showing oxygen saturation of at least 90% on room air No irreversible coagulopathy, international normalized ratio (INR) =< 2 No sign of tumor lysis syndrome, uric acid needs to be in normal range prior to treatment Not in diabetic ketoacidosis (DKA), sickle cell crisis, and not having severe peripheral vascular disease on active anti-coagulation treatment Exclusion Criteria: Pregnant or nursing women; women who still have child-bearing potential must be tested for urinary or serum beta human chorionic gonadotropin (βHCG) Biological or chemotherapy in the 4 weeks prior to the start of dosing Patients with intrinsic immunosuppression, including seropositivity for human immunodeficiency virus (HIV) antibody; patients should be tested for HIV Serious concurrent infection, including active tuberculosis, hepatitis B, or hepatitis C; patients should be tested for hepatitis B surface antigen and hepatitis C antibody; patients who are hepatitis C antibody (Ab) positive can be eligible if they are PCR negative Active or history of confirmed autoimmune disease Concurrent systemic corticosteroids (except physiologic replacement doses) or other immunosuppressive drugs (eg. cyclosporin A) Active or history of autoimmune disease including but not limited to rheumatoid arthritis (rheumatoid factor [RF]-positive with current or recent flare), inflammatory bowel disease, systemic lupus erythematosus (clinical evidence with antinuclear antibody [ANA] 1:80 or greater), ankylosing spondylitis, scleroderma, multiple sclerosis, autoimmune hemolytic anemia, and immune thrombocytopenic purpura; seropositivity alone will not be considered positive Psychiatric illness that may make compliance to the clinical protocol unmanageable or may compromise the ability of the patient to give informed consent; patients with clinical evidence of dementia should have a competent designee participate in decision

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A (vaccine with Montanide)<br>Patients receive WT1 126-134 peptide vaccine emulsified in Montanide ISA 51 VG SC on day 0 and then once every 2 weeks. | Biological: WT1 126-134 peptide vaccine<br>* Given SC<br>Drug: Montanide ISA 51 VG<br>* Given SC<br>Other: laboratory biomarker analysis<br>* Correlative studies<br>|
| Experimental: Arm B (vaccine with poly-ICLC)<br>Patients receive WT1 126-134 peptide vaccine in poly-ICLC SC on day 0 and then once every 2 weeks. | Biological: WT1 126-134 peptide vaccine<br>* Given SC<br>Drug: poly ICLC<br>* Given SC<br>* Other names: stabilized polyriboinosinic/polyribocytidylic acid;Other: laboratory biomarker analysis<br>* Correlative studies<br>|
| Experimental: Arm C (vaccine therapy, monoclonal antibody)<br>Patients assigned to Arm C receive basiliximab IV over 30 minutes on day -7 and WT1 126-134 peptide vaccine as in Arm A or Arm B, whichever had a superior cellular immune response. | Biological: basiliximab<br>* Given IV<br>* Other names: Simulect;Biological: WT1 126-134 peptide vaccine<br>* Given SC<br>Drug: Montanide ISA 51 VG<br>* Given SC<br>Drug: poly ICLC<br>* Given SC<br>* Other names: stabilized polyriboinosinic/polyribocytidylic acid;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of peptide specific immunologic response between regimens | Evaluated by flow cytometry and using IFN-gamma ELISPOT as the primary measures. Compared using a two-sample t test. | Over 9 months | 
| Comparison of regulatory T cells (Treg) number changes between regimens | Evaluated by flow cytometry and using interferon (IFN)-gamma Enzyme-linked immunosorbent spot (ELISPOT) as the primary measures. Compared using a two-sample test. The Treg cell counts and percentage by flow cytometry, the FoxP3 expression by qRT-PCR, and the peptide specific CD8+cell level by ELISPOT will be measured continuously prior to basiliximab and WT1 126-134 peptide vaccine and after basiliximab and/or WT! 126-134 peptide vaccine. | 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Molecular response in terms of WT1 expression |  | Every 12 weeks for 1 year after stopping treatment | 
| Relapse-free survival |  | Every 12 weeks for 1 year after stopping treatment |