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

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

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

Study Overview

• Status: Completed
• Conditions: 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
• Intervention / Treatment: Other: laboratory biomarker analysis; Biological: WT1 126-134 peptide vaccine; Drug: Montanide ISA 51 VG; Drug: poly ICLC; Biological: basiliximab

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.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637-1470
      • University of Chicago

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A (vaccine with Montanide); Patients receive WT1 126-134 peptide vaccine emulsified in Montanide ISA 51 VG SC on day 0 and then once every 2 weeks.	Other: laboratory biomarker analysis; Correlative studies; Biological: WT1 126-134 peptide vaccine; Given SC; Drug: Montanide ISA 51 VG; Given SC
Experimental: Arm B (vaccine with poly-ICLC); Patients receive WT1 126-134 peptide vaccine in poly-ICLC SC on day 0 and then once every 2 weeks.	Other: laboratory biomarker analysis; Correlative studies; Biological: WT1 126-134 peptide vaccine; Given SC; Drug: poly ICLC; Given SC; Other Names: Hiltonol; poly I:poly C with poly-1-lysine stabilizer; Polyinosinic-Polycytidylic Acid Stabilized with Polylysine and Carboxymethylcellulose; stabilized polyriboinosinic/polyribocytidylic acid
Experimental: Arm C (vaccine therapy, monoclonal antibody); 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.	Other: laboratory biomarker analysis; Correlative studies; Biological: WT1 126-134 peptide vaccine; Given SC; Drug: Montanide ISA 51 VG; Given SC; Drug: poly ICLC; Given SC; Other Names: Hiltonol; poly I:poly C with poly-1-lysine stabilizer; Polyinosinic-Polycytidylic Acid Stabilized with Polylysine and Carboxymethylcellulose; stabilized polyriboinosinic/polyribocytidylic acid; Biological: basiliximab; Given IV; Other Names: Simulect; SDZ-CHI-621

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	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

Collaborators and Investigators

• Sponsor: University of Chicago
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Hongtao Liu, University of Chicago

Publications and helpful links

General Publications

• Liu H, Zha Y, Choudhury N, Malnassy G, Fulton N, Green M, Park JH, Nakamura Y, Larson RA, Salazar AM, Odenike O, Gajewski TF, Stock W. WT1 peptide vaccine in Montanide in contrast to poly ICLC, is able to induce WT1-specific immune response with TCR clonal enrichment in myeloid leukemia. Exp Hematol Oncol. 2018 Jan 11;7:1. doi: 10.1186/s40164-018-0093-x. eCollection 2018.

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2011
• Primary Completion (Actual): February 2, 2015
• Study Completion (Actual): March 1, 2018

Study Registration Dates

• First Submitted: July 3, 2012
• First Submitted That Met QC Criteria: April 24, 2013
• First Posted (Estimate): April 29, 2013

Study Record Updates

• Last Update Posted (Actual): March 9, 2018
• Last Update Submitted That Met QC Criteria: March 7, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Adjuvants, Immunologic; Interferon Inducers; Laxatives; Poly ICLC; Basiliximab; Carboxymethylcellulose Sodium; Poly I-C; Monatide (IMS 3015)
• Other Study ID Numbers: 11-0545; NCI-2011-03588 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No