Table 1.

Recruiting, Active and Recently Completed Vaccine Clinical Trials in Acute Myeloid Leukemia

Agent	Sponsor	Details	Patients	Primary Endpoints	Secondary Endpoints	Status	NCT ID
WT-1 Peptide Vaccine	Memorial Sloan-Kettering Cancer Center	Peptides/Montanide and GM-CSF injected SC in weeks 0, 4, 6, 8, 10, and 12. If immune response and no disease progression up to 6 additional monthly doses.	AML (in CR, with no plans for additional chemotherapy) or MDS (≥Int-2, not candidate for chemotherapy) with documented pretreatment WT-1 positive disease (by protein on bone marrow biopsy or RQ-PCR).	Safety Immune (D, Ie, P, T)	Tumor response	Completed Phase I	NCT00398138
WT-1 peptide Vaccine	Memorial Sloan-Kettering Cancer Center	6x SC vaccinations with WT1 peptide over ten week period.	AML in first CR, completed post-remission therapy, not eligible for allo-BMT, with WT-1 positive PCR detectable MRD on bone marrow within 4wks of 1st vaccine.	Safety OS (3yr)	DFS (3yr) Immune (T, P, If/e) MRD (WT-1+ by RT-PCR)	Recruiting Phase II Opened Dec 2010	NCT01266083
WT-1 derived Peptides	Duke University	WT-1 derived epitopes restricted by HLA-A2, A24, DR15 and DRw53 injected ID and SC in Montanide and GM-CSF.	Following autologous or allogeneic stem cell transplantation for AML, CML, ALL, B cell malignancies or MDS. Patient must be HLA A2, A24, DR15 or DRw53.	Safety Feasibility	Immune Clinical response	Recruiting Phase I Opened June 2007	NCT00672152
WT-1 Peptide	H. Lee Moffitt Cancer Center	6 bi-weekly vaccinations of peptide/montanide and GM-CSF over 10 weeks. Patients with immunologic response and not disease progression may continue with 6 extra monthly vaccinations.	AML (in CR1 or 2, with no plans for additional chemotherapy) or MDS (≥Int-2, not candidate for chemotherapy) with documented pretreatment WT-1 positive disease (by protein on bone marrow biopsy or RQ-PCR).	Safety Toxicity Immune (D, In, P, T)	Tumor Response (WT-1+ by IHC and RQ-PCR, Multiparameter Flow Cytometry)	Recruiting Opened June2008	NCT00665002
WT-1 peptide vaccine with lymphodepletion and lymphocyte infusion.	National Heart, Lung, and Blood Institute (NHLBI)	Peptide/Montanide and GM-CSF injections weekly for 9 wks.	MDS, CML (relapsed or refractory, with accelerated or blast phase), AML (secondary, relapsed or refractory) ALL (relapsed, refractory or in CR), CMML. HLA-A0201+	Efficacy (change in frequencies of circulating WT-1 specific T cells) Toxicity	Hematological (marrow blasts, blood counts, transfusion dependence) TTP OS	Completed Phase II	NCT00433745
WT-1 epitopes DNA vaccine	Southampton University Hospitals NHS Trust	If HLA A2+ will be vaccinated with two DNA vaccines given IM followed by electroporation, 6 times at 4 weekly intervals followed by every 3 month vaccinations (for max of 24 mo) in responders. HLA A2-ve patients monitored with molecular testing only.	CML: Philadelphia chromosome positive CML in chronic phase, maintained in complete cytogenetic response (CCyR) for ≥ 24months but with detectable BCR-ABL transcripts. AML patients: AML: WT1+ AML in CR or morphologic CR with incomplete blood count recovery (CRi).	Molecular Response	CML: TTP TNT 2yr Survival AML: 2yr Survival OS	Recruiting Phase II Opened Feb 2010	NCT01334060
WT-1 Peptide Fusion Protein	GlaxoSmith-Kline	Recombinant fusion protein WT1-A10 combined with the adjuvant ASO1B GSK2130579A	Post-induction therapy in adults with WT1-positive AML and a suboptimal clinical response (PR or CRi) to induction chemotherapy	Severe Toxicity Clinical Activity	Immune Safety Clinical Activity	Recruiting Phase 1	NCT0151063
WT-1 Peptide Fusion Protein	GlaxoSmith-Kline	Recombinant fusion protein WT1-A10 combined with the adjuvant ASO1B GSK2130579A	Post-consolidation therapy in adults with WT1-positive AML in first complete remission	Severe Toxicity Immune (H/S)	Adverse Events	Recruiting Phase 1	NCT00725283
WT-1 Peptide-Pulsed Dendritic Cells	National Cancer Institute (NCI)	Donor-derived dendritic cell/WT-1 vaccine and DLI given every 14 days for 6 doses.	HLA-A2 plus patients aged 1 to 75 with relapsed or residual WT1 expressing hematologic malignancy following (at least 5/6 match) allogeneic SCT Donor also HLA-A2 plus.	Safety Toxicity Feasibility	Immune Clinical response MRD (WT-1+ by RT-PCR)	Recruiting Phase I/II Opened Jan 2008	NCT00923910
WT1 and PR1 Peptide Vaccine	National Heart, Lung, and Blood Institute (NHLBI)	Single dose of PR1:169–177 and WT-1:126–134 peptide (in Montanide) concomitantly with GM-CSF	HLA-A*0201 positive. AML in CR (w/in 5yrs of treatment), CP CML, MDS, Between 6–36 months from allo-BMT for MDS, CML, AML with 100% engraftment and <5% blasts in marrow.	Safety	N/A	Completed Phase I	NCT00270452
WT-1 and PR-1 Peptide Vaccines	National Heart, Lung, and Blood Institute (NHLBI)	Six doses of a combination of WT-1: 126–134 and PR-l: 169–177 peptide vaccines in Montanide and GM-CSF	HLA-A*0201 positive. MDS, AML in CR or CP CML and unsuitable for stem cell transplantation or at 6–36 mos after Allo-BMT with <5% blasts in marrow, 100% engraftment	Efficacy (change in frequencies of circulating PR-1 and WT-1 specific T cells) Toxicity	Hematological (marrow blasts, blood counts, transfusion dependence) TTP OS Boost Response	Completed Phase II Ref: (92)	NCT00488592
PR-1 Peptide Vaccine	M.D. Anderson Cancer Center	PR1 peptide SC with Montanide and GM-CSF every 3 weeks for total of 6 vaccinations.	HLA-A*0201 positive patients with high risk myeloid leukemias.	Immune (3wk after last vaccine) Clinical (3wk after last vaccine)	EFS OS	Ongoing, but not recruiting Phase I/II Opened Dec 1999	NCT00004918
Dendritic Cell/AML Vaccine and either PD-1 blockade or GM-CSF	Beth Israel Deaconess Medical Center/NIH/CureTech Ltd	CT-011 (anti PD-1 mAb) or GM-CSF 4–8wks after chemotherapy. Followed by 3 doses of DC/AML vaccine given at 4wk intervals.	AML (initial diagnosis or relapse) in chemotherapy induced CR.	Toxicity	Immune (D) TTP (2yrs)	Recruiting Phase II Opened May 2010	NCT01096602
GM-CSF/K562 with irradiated autologous leukemia vaccine.	Dana-Farber Cancer Institute	K562 expressing GM-CSF mixed with irradiated autologous leukemia. Total of 6 doses over 9 wks.	Advanced Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML) after Allogeneic Hematopoetic Stem Cell Transplantation	Safety	Immune (D) Disease Response DFS OS	Recruiting Phase I Opened Nov 2008	NCT00809250
Lentivirus Transduced AML Blasts to express B7.1 (CD80) & IL-2	King’s College Hospital NHS Trust, London.	RFUSIN2-AML1 (AML Blasts transduced to express B7.1 and IL-2) and/or DLI.	New or relapsed poor prognosis AML with no CR or persistent cytogenetic abnormality >100 days post BMT.	Safety and Toxicity	Relapse LFS OS	Recruiting Phase I Opened May 2008	NCT00718250
GM-CSF/K562 with irradiated autologous leukemia vaccine, before and after Auto-PBSC and primed DLI.	Cell Genesys	Autologous leukemia admixed with GM-CSF secreting K562 (“GVAX”) given once pre-and every 3wks for 8 doses starting ≥ 6wks post-auto-BMT. Primed autologous DLI with PBSC.	De novo, untreated, AML in patients 18–60 with 18 and 60 years of age.	Safety Feasibility	GM-CSF PKData Immune (A, D, H, If,) MRD(WT-1+ by RT-PCR) RFS OS	Completed Phase II Ref: (108)	NCT00116467
WT-1 mRNA-transfected Autologous Dendritic Cell Vaccination	University Hospital, Antwerp	Intradermal injection of WT1-RNA-transfected autologous dendritic cells.	Adults with AML or MDS, with over-expression of WT-1, in PR, CR or smoldering course and high risk of relapse.	Toxicity Feasibility	Immune	Completed Phase I/II	NCT00834002
BMT followed by autologous cancer vaccine and donor DLI.	SKCCC at Johns Hopkins	HLA matched related sibling nonmyeloablative hematopoietic stem cell transplantation followed by autologous tumor cell vaccine +/− DLI from donor.	AML: Relapsed, from MDS, Primary Refractory or De Novo with High Risk Features. ALL: Ph chromosome +, t(4,11) or relapsed. Multiple Myeloma: In need of treatment.	TTP	Safety and Tolerability Determine MTD of DLI	Completed	NCT00469820
Autologous Mature Dendritic Cells transfected with hTERT mRNA	Geron Corporation	Vaccinated weekly for 6 weeks, “rest” for 4 weeks, then 6 boost injections over 12 weeks.	AML in first CR or in CR2 with CR1 >/= 6 months Has completed at least one cycle of consolidation chemotherapy within past 6 months.	Feasibility	Immune (D, S) EFS	Active, Not Recruiting Phase II Opened July 2007	NCT00510133
Therapeutic autologous dendritic cells.	Institut Paoli-Calmettes	Increasing doses of blastic cells transformed in vitro by autologous dendritic cells (1/3 subcutaneously and 2/3 IV) every 3 weeks for up to 5 doses.	HLA-A*0201 positive. AML, M4 or M5, in CR2 or later following CR1 lasting <12months. Not Eligible for BMT.	Tolerability	Immune Clinical Response	Active, Not Recruiting Phase I	NCT00963521
BMT followed by irradiated autologous myeloblastic leukemia engineered to secrete GM-CSF	Dana-Farber Cancer Institute	Allogeneic reduced intensity stem cell transplant followed 30–45 days later by vaccination SC and ID 6 times over a period of 9 weeks.	AML, MDS-RAEB or RAEB-T, CML, myeloid blast crisis not in remission or CML accelerated phase. Subjects must have > 5% blasts in bone marrow or peripheral blood prior to admission for transplant. HLA 6/6 matched related or unrelated donor available	Feasibility	Safety Biological activity DFS OS	Active, Not Recruiting Opened June 2004	NCT00426205
Irradiated autologous myeloblastic leukemia engineered to secrete GM-CSF	Dana-Farber Cancer Institute	Vaccinations will be given weekly for three weeks, followed by every other week, for a min of 6 doses.	MDS, AML (relapsed, refractory, not candidate for myelosuppressive chemotherapy).	Feasibility	Safety Biological Activity	Completed Phase I	NCT00136422

Key

AML = Acute Myeloid Leukemia

DC = Dendritic Cell

DLI = Donor Lymphocyte Infusion

DFS = Disease Free Survival

EFS= Event Free Survival

ID = Intradermally

IM = Intramuscular

LFS = Leukemia Free Survival

MRD = minimal residual disease

OS = Overall Survival

PD-1 = Programmed death-1 receptor

RFS = Relapse Free Survival

SC = Subcutaneous

TNT = Time to next treatment

TTP = Time to Progression

WT-1 = Wilms Tumor Antigen

Immune Monitoring

A = Skin Test Anergy Panel

D = Delayed Type Hypersensitivity Testing (DTH)

H= Humeral/Antibody Response

If = IFN-Y Cytokine Assay - Flow

Ie = IFN-Y Cytokine Assay – Elispot

In = IFN-Y Cytokine – Assay Not Specificed

P = CD4 Proliferation Assay

S= Measurement of Antigen Specific T cells – Assay not specificied.

T = MHC Tetramer Assay