ADVANCE-II: Efficacy and Safety of Immunotherapy With Allogeneic Dendritic Cells, DCP-001, in Patients With Acute Myeloid Leukaemia

Sponsor

DCPrime BV (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03697707

Collaborator

Amsterdam UMC, location VUmc (Other)

Enrollment

Locations

Arms

49.5

Anticipated Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Phase II study to evaluate safety and efficacy of DCP-001 in patients with AML in CR, and with presence of MRD

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia in Remission	Biological: DCP-001	Phase 2

Detailed Description

International, multicentre, open-label proof of concept study exploring two different dose groups of the allogeneic dendritic cell vaccine, DCP-001. Cohort 1 consists of 10 patients that will receive 25E6 DCP-001 cells per vaccination and Cohort 2 consists of 10 patients who will receive 50E6 DCP-001 cells per vaccination. All patients will be given two additional booster vaccinations of 10E6 cells. Each patient will be followed up for 12 months after the 4th vaccination. Safety will be monitored throughout the study. Sera and cell samples (blood and bone marrow) will be collected for assessment of efficacy (MRD evaluation) and immune response monitoring.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Intervention Model Description:

First 10 patients will get the lowest dose and next 10 patients will receive the highest doseFirst 10 patients will get the lowest dose and next 10 patients will receive the highest dose

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An International, Multicentre, Open-label Study To Evaluate The Efficacy and Safety of Two Different Vaccination Regimens of Immunotherapy With Allogeneic Dendritic Cells, DCP-001, in Patients With Acute Myeloid Leukaemia That Are In Remission With Persistent MRD

Actual Study Start Date :

Oct 15, 2018

Anticipated Primary Completion Date :

Mar 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1: Low dose patients receiving 4 bi-weekly vaccinations with 25E6 cells/vaccination of DCP-001, and 2 booster vaccinations with 10E6 cells/vaccination	Biological: DCP-001 allogeneic dendritic cell vaccine
Experimental: Cohort 2: High dose patients receiving 4 bi-weekly vaccinations with 50E6 cells/vaccination of DCP-001, and 2 booster vaccinations with 10E6 cells/vaccination	Biological: DCP-001 allogeneic dendritic cell vaccine

Arm

Intervention/Treatment

Experimental: Cohort 1: Low dose

patients receiving 4 bi-weekly vaccinations with 25E6 cells/vaccination of DCP-001, and 2 booster vaccinations with 10E6 cells/vaccination

Biological: DCP-001

allogeneic dendritic cell vaccine

Experimental: Cohort 2: High dose

patients receiving 4 bi-weekly vaccinations with 50E6 cells/vaccination of DCP-001, and 2 booster vaccinations with 10E6 cells/vaccination

Biological: DCP-001

allogeneic dendritic cell vaccine

Outcome Measures

Primary Outcome Measures

minimal residual disease (MRD) [up to 32 weeks]
Any change in MRD (flow cytometric) as compared to baseline MRD

Secondary Outcome Measures

Treatment emergent adverse events (TEAEs) [up to 56 weeks]
adverse event
Serious Adverse Events (SAEs) [up to 56 weeks]
adverse events
Relapse-free survival [up to 56 weeks]
efficacy
Overall survival [up to 56 weeks]
efficacy
Immune responses [up to 32 weeks]
Any change in immunoreactivity (specific and non-specific) as compared to baseline

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Confirmed diagnosis of AML according to WHO2016 criteria, including cytological, molecular and cytogenetic criteria (except acute pro-myelocytic leukaemia/APL).
In CR1 (first complete remission) or CRi (incomplete blood count recovery) documented by bone marrow examination up to one month before vaccination; CR defined as less than 5% blasts in normo-cellular bone marrow, ANC >1E9/L, platelet count >100E9/L, no evidence of extra-medullary disease. Patients in CRi (patients with <5% blasts but with incomplete blood count recovery) should have platelets >50 E9/L.
MRD as defined by multicolour flow cytometry (MFC) at a value of > 0.1%, or detection of specific molecular abnormalities such as NPM1 mutation.
Patients that are in CR1 or CRi. Patients not having undergone consolidation therapy must have been in CR1 for at least 1 month prior to enrolment. Patients treated with hypomethylating agents must have been given at least two cycles and up to a maximum of nine cycles of hypomethylating agents.
Expected and willing to undergo all study procedures, including outpatient evaluations for clinical and immunological monitoring.
Male or female of ≥ 18 years of age.
Women of childbearing potential must be using anti-conceptive therapy or use two (2) barrier contraceptive methods (one by each partner and at least one of the barrier methods must include spermicide (unless spermicide is not approved in the country or region). See section 12.7 for birth control methods deemed acceptable for this study.
ECOG (WHO) performance status 0-2.
Willing and able to provide written informed consent for participation in the study

Exclusion Criteria:

Acute Promyelocytic (APL; M3) type of AML.
Patients who have undergone or are scheduled/eligible for allogeneic stem cell transplantation.
History of previous allogeneic bone marrow or solid organ transplantation.
Uncontrolled or serious infections
Ongoing immunosuppressive therapy, other than short use of low dose steroids, i.e. equivalent to an average dose of ≤10mg of prednisone/day.
Chemotherapy and antineoplastic hormonal therapy within 28 days prior to the screening visit, with the exception of hypomethylating agents such as azacitidine and decitabine, or midostaurin for FLT3 mutations, or patients treated with IDH12 inhibitors in mIDH1/2.
Current or past medical history autoimmune disease.
Inadequate liver function (AST and ALT > 3 x ULN, serum bilirubin >3 x ULN).
Other active Malignancies within the last 5 years, except for adequately treated carcinoma in situ of the cervix or squamous carcinoma of the skin or adequately controlled limited basal cell skin cancer.
Pregnant or lactating females.
Major surgical procedure (including open biopsy) within 28 days prior to the first study treatment, or anticipation of the need for major surgery during the course of the study treatment.
Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm Hg) or clinically significant (i.e. active) cardiovascular disease.
Evidence of any other medical conditions (such as psychiatric illness, physical examination or laboratory findings) that may interfere with the planned treatment, affect patient compliance or place the patient at high risk from treatment-related complications.
Known HIV, Hepatitis B and/or Hepatitis C infections.
History of hypersensitivity to the investigational medicinal product or to any excipient present in the pharmaceutical form of the investigational medicinal product.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Helsinki University Hospital	Helsinki	Finland
2	Universitats Klinikum Bonn	Bonn	Germany
3	Marien Hospital	Düsseldorf	Germany	D- 40479
4	Universitats Klinikum Leipzig	Leipzig	Germany
5	Universitätsmedizin Mainz	Mainz	Germany
6	VUmc	Amsterdam	Netherlands
7	UMCG	Groningen	Netherlands
8	Maastricht University Medical Centre	Maastricht	Netherlands
9	Haukeland universitetssjukehus	Bergen	Norway
10	Uppsala University Hospital	Uppsala	Sweden