search
Back to results

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

Primary Purpose

Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q)

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
basiliximab
WT1 126-134 peptide vaccine
Montanide ISA 51 VG
poly ICLC
laboratory biomarker analysis
Sponsored by
University of Chicago
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adult Acute Myeloid Leukemia in Remission

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Chicago

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Arm A (vaccine with Montanide)

Arm B (vaccine with poly-ICLC)

Arm C (vaccine therapy, monoclonal antibody)

Arm Description

Patients receive WT1 126-134 peptide vaccine emulsified in Montanide ISA 51 VG SC on day 0 and then once every 2 weeks.

Patients receive WT1 126-134 peptide vaccine in poly-ICLC SC on day 0 and then once every 2 weeks.

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.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Molecular response in terms of WT1 expression
Relapse-free survival

Full Information

First Posted
July 3, 2012
Last Updated
March 7, 2018
Sponsor
University of Chicago
Collaborators
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT01842139
Brief Title
Vaccine Therapy and Basiliximab in Treating Patients With Acute Myeloid Leukemia in Complete Remission
Official Title
Randomized Phase I Study Combining Suppression of T Regulatory Cells With WT1 Vaccine Therapy for AML Patients in Complete Remission
Study Type
Interventional

2. Study Status

Record Verification Date
March 2018
Overall Recruitment Status
Completed
Study Start Date
December 5, 2011 (Actual)
Primary Completion Date
February 2, 2015 (Actual)
Study Completion Date
March 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Chicago
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
7 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A (vaccine with Montanide)
Arm Type
Experimental
Arm Description
Patients receive WT1 126-134 peptide vaccine emulsified in Montanide ISA 51 VG SC on day 0 and then once every 2 weeks.
Arm Title
Arm B (vaccine with poly-ICLC)
Arm Type
Experimental
Arm Description
Patients receive WT1 126-134 peptide vaccine in poly-ICLC SC on day 0 and then once every 2 weeks.
Arm Title
Arm C (vaccine therapy, monoclonal antibody)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
basiliximab
Other Intervention Name(s)
SDZ-CHI-621, Simulect
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
WT1 126-134 peptide vaccine
Intervention Description
Given SC
Intervention Type
Drug
Intervention Name(s)
Montanide ISA 51 VG
Intervention Description
Given SC
Intervention Type
Drug
Intervention Name(s)
poly ICLC
Other Intervention Name(s)
Hiltonol, poly I:poly C with poly-1-lysine stabilizer, Polyinosinic-Polycytidylic Acid Stabilized with Polylysine and Carboxymethylcellulose, stabilized polyriboinosinic/polyribocytidylic acid
Intervention Description
Given SC
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Comparison of peptide specific immunologic response between regimens
Description
Evaluated by flow cytometry and using IFN-gamma ELISPOT as the primary measures. Compared using a two-sample t test.
Time Frame
Over 9 months
Title
Comparison of regulatory T cells (Treg) number changes between regimens
Description
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.
Time Frame
9 months
Secondary Outcome Measure Information:
Title
Molecular response in terms of WT1 expression
Time Frame
Every 12 weeks for 1 year after stopping treatment
Title
Relapse-free survival
Time Frame
Every 12 weeks for 1 year after stopping treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hongtao Liu
Organizational Affiliation
University of Chicago
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637-1470
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
29344432
Citation
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.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs