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


Phase 1
18 Years
85 Years
Open (Enrolling)
Both
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)

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Trial Information

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


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.


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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Comparison of peptide specific immunologic response between regimens

Outcome Description:

Evaluated by flow cytometry and using IFN-gamma ELISPOT as the primary measures. Compared using a two-sample t test.

Outcome Time Frame:

Over 9 months

Safety Issue:

No

Principal Investigator

Hongtao Liu

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Chicago

Authority:

United States: Institutional Review Board

Study ID:

11-0545

NCT ID:

NCT01842139

Start Date:

December 2011

Completion Date:

December 2015

Related Keywords:

  • 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)
  • Congenital Abnormalities
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid

Name

Location

University of ChicagoChicago, Illinois  60637