Primary:• To assess the effect of DCP-001 on MRD. MRD will be measured by flow cytometry pre and post vaccination as a surrogate marker for established clinical endpoints in AML.• To assess the effect of DCP-001 on immune responses in AML patients…
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Any change in MRD (flow cytometric) as compared to baseline MRD
- Any change in immunoreactivity (specific and non-specific) as compared to
baseline.
Secondary outcome
Secondary Efficacy Endpoints
- To document safety and tolerability.
- To quantify any lag time between initiation of treatment & onset of effect.
- To determine the effect of DCP-001 on Time to Relapse (TTR).
- To determine the effect of DCP-001 on Overall Survival (OS).
- To document the difference between the two vaccination regimens based on MRD
outcome and immunological parameters.
Exploratory Endpoints
- To document the number and duration of subsequent remissions.
- To identify subgroups of patients most likely to benefit from treatment.
- To identify surrogate (immunological) markers that might correlate with
clinical outcome.
- To quantify any lag time between initiation of treatment & onset of effect
- To identify surrogate (immunological) markers that might correlate with
clinical outcome.
Safety endpoints:
- Treatment emergent adverse events (TEAEs) will be collected in first 48 hours
after the first vaccination to determine (acute) toxicity due to intradermal
injection.
- All TEAEs will be collected during the study period for each patient and the
grade of toxicity (CTCAE v.4.0, see Appendix B) and relationship to product
determined.
- A DSMB will meet after every 5 patients complete treatment to evaluate
safety; written reports will be made of each meeting.
- All SAEs will be reported by the investigator within 24 hours of the first
knowledge. All SAEs will be reported in a timely manner to the appropriate
regulatory body, consistent with existing regulations. Information on relevant
SAEs will be disseminated between sites in a timely manner. Processes are
described in detail in the study specific safety plan.
Background summary
Immunotherapy offers promise in AML and has created opportunities for improved
outcomes. Dendritic cell (DC)-based immunotherapy has shown to be a promising
strategy for the elimination of minimal residual disease (MRD) in patients with
acute myeloid leukemia (AML).
DCP-001 is an allogeneic dendritic cell based immunotherapeutic vaccine that
expresses a number of tumor antigens that are expressed in AML and have shown
clinical results when applied as peptide vaccines or loaded onto patient
derived DC's.
Evidence for DCP-001 mediated safety, feasibility and immunological responses
have been demonstrated in a Phase I study; the current study aims to generate
evidence for clinical efficacy.
Study objective
Primary:
• To assess the effect of DCP-001 on MRD. MRD will be measured by flow
cytometry pre and post vaccination as a surrogate marker for established
clinical endpoints in AML.
• To assess the effect of DCP-001 on immune responses in AML patients in first
complete remission (CR1) and persistent MRD.
• To document safety and tolerability.
Secondary:
• To identify surrogate (immunological) markers that might correlate with
clinical outcome.
• To quantify any lag time between initiation of treatment & onset of effect.
• To determine the effect of DCP-001 on Time to Relapse (TTR).
• To determine the effect of DCP-001 on Overall Survival (OS) during the study.
• To document the difference between the two vaccination regimens based on MRD
outcome and immunological parameters.
Study design
International, multicenter, open-label proof of concept study without
randomization and stratification. Two different dose groups are included. Group
1 consists of 10 patients that will receive 25E6 DCP-001 cells per vaccination
with two additional booster vaccinations of 10E6 cells.
Group 2 consists of 10 patients who will receive 50E6 DCP-001 cells per
vaccination with two additional booster vaccinations of 10E6 cells.
Patients will be screened for eligibility for the study and evaluated at
baseline, at each vaccination visit and every 8 weeks during follow up. Each
patient will be followed up for 12 months after the 4th vaccination, and will
subsequently be asked to prolong the follow up up until five years after first
vaccination. Sera and cell samples (blood and bone marrow) will be collected
when indicated for efficacy (MRD evaluation) and immune response monitoring.
Intervention
Patients will receive 25E6 DCP-001 cells per vaccination (Group 1; 10 patients)
or 50E6 DCP-001 cells (Group 2; 10 patients) per vaccination. Both groups will
receive two additional booster vaccination of 10E6 cells.
The first treatment for both dose groups is given at Day 0 (Baseline), the
second, third and fourth treatments are given at 2 weekly intervals. A total of
4 treatments will be administered in a 6 week timeframe followed by a booster
vaccination at 8 and 12 weeks after the 4th vaccination at week 6. A summary of
the treatment schedule is given below:
Study burden and risks
The Phase I study with DCP-001 has not generated any safety concerns.
This study involves administration of a therapeutic agent which could provide
an efficacious treatment for patients. Both active treatment arms are expected
to provide therapeutic benefit for patients. It is therefore concluded that the
risk-benefit ratio for patients entering this study is favorable.
Risk of infection:
Risk is considered low/absent as the DCOne cell line from which DCP-001 derived
has been extensively tested for multiple viruses according to applicable
regulatory guidelines (see IB/IMPD). Upon release the DCP-001 product is
confirmed to be sterile.
Emmy Noetherweg 2K 2K
Leiden 2333BK
NL
Emmy Noetherweg 2K 2K
Leiden 2333BK
NL
Listed location countries
Age
Inclusion criteria
1. Confirmed diagnosis of AML according to WHO2016 criteria, including
cytological, molecular and cytogenetic criteria (except acute promyelocytic
leukemia/APL).
2. In CR1 or CRi documented by bone marrow examination up to one month before
vaccination; CR defined as less than 5% blasts in normo-cellular bone marrow,
ANC >1*10E9/L, platelet count 100*E9/L, no evidence of extra-medullary disease.
Patients in CRi (patients with <5% blasts but with incomplete blood count
recovery) should have platelets >50 G/L.
3. MRD as defined by multicolor flow cytometry (MFC) at a value of > 0.1% or
detection of specific molecular abnormalities such as NPM1 mutation.
4. Patients that are in CR1 or CRi. Patients not having undergone consolidation
therapy must have been in CR1 or CRi 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.
5. Expected to be willing and able to undergo all study procedures, including
outpatient evaluations for clinical and immunological monitoring.
6. Male or female > 18 years of age.
7. Women of childbearing potential must be on anti-conceptive therapy, or using
an intrauterine device, 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), or underwent
tubal ligation, or the partner was vasectomized, or is sexually abstinent.
8. ECOG (WHO) performance status 0-2.
9. Willing and able to provide written informed consent for participation in
the study and for tissue sample biobanking..
Exclusion criteria
1. APL (M3) type of AML.
2. Patients who have undergone or are scheduled/eligible for allogeneic stem
cell transplantation.
3. History of previous allogeneic bone marrow or solid organ transplantation.
4. Uncontrolled or serious infections
5. Ongoing immunosuppressive therapy, other than short use of low dose
steroids, i.e. equivalent to an average dose of <=10mg of prednisone/day.
6. Chemotherapy and antineoplastic 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 IDH1/2 inhibitors in mIDH1/2.
7. Current or past medical history of autoimmune disease.
8. Inadequate liver function (AST and ALT > 3 x ULN, serum bilirubin >3x ULN).
9. 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.
10. Pregnant or lactating females.
11. 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.
12. Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm
Hg) or clinically significant (i.e. active) cardiovascular disease.
13. 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.
14. Known HIV, Hepatitis B or C infections.
15. History of hypersensitivity to the investigational medicinal product or to
any excipient present in the pharmaceutical form of the investigational
medicinal product
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | 2017-003426-17 |
| EudraCT | EUCTR2017-003426-32-NL |
| CCMO | NL62714.000.17 |