Phase 1 Study of Leukemic Dendritic Cell Vaccination in Patients With Acute Myeloid Leukemia
18 Years
80 Years
Both
Acute Myeloid Leukemia (AML), Leukemic Dendritic Cell Vaccination
Trial Information
Phase 1 Study of Leukemic Dendritic Cell Vaccination in Patients With Acute Myeloid Leukemia
DCPrime is testing an allogeneic (non-self cells, standardised product) DC-based
immunotherapy in cancer patients. The technology consists of sustainable dendritic
progenitor cells (named "DCOne™") and a proprietary method to expand these and to create
functional mature dendritic cells (DCP-001).
AML is a fast growing form of leukemia that particularly in the elderly (>60) is life
threatening. As age is an important factor in determining the success of AML treatment,
overall, AML has a bad prognosis as only 24% of the patients are alive 5 years after
diagnosis.
Without treatment AML is fatal, usually within months. Chemotherapy can cure patients and
prolong survival in responders; however, chemotherapy is also quite toxic and can cause
substantial morbidity and mortality. The most commonly prescribed first line therapy for
patients with AML is a combination of an anthracycline and cytarabine; in the Western world
the anthracycline is either daunorubicin or idarubicin. Post remission therapy
(consolidation therapy) is usually given.
There is therefore substantial medical need for new treatment modalities. One of the major
difficulties regarding development of new agents is that relatively low response rates and
toxicity issues have been in the way of approval of new agents. Immunotherapy, in particular
with the therapeutic vaccines, is expected to have potential in prevention of recurrence of
disease after cytoreductive therapy. Any drug that could prevent or reduce minimal residual
disease in the population is likely to meet a strong medical need for this population of
high risk patients.
In this phase 1 trial consecutive eligible patients will be treated until 12 patients have
completed the study. Patients will be started with the vaccination program within 2 months
after having achieved complete remission or in patients who have stable disease over at
least a 2 month period.
The first cohort (n=3) will receive 4 bi-weekly vaccinations of 1x10E7 DCP-001, the second
cohort (n=3) will receive 4 bi-weekly vaccinations of 2.5x10E7 DCP-001, and the last cohort
(n=3) will receive 4 bi-weekly vaccinations of 5x10E7 DCP-001. The Dose Limiting Toxicity
(DTL) is defined as non-hematological toxicity of ≥ 3 according to common toxicity criteria
v3.0. The 4th cohort (matched for HLA-A2) will receive 4 vaccinations of the highest dose
(5x10E7 DCP-001) or, in case this turned out to be toxic (as determined by the vaccination
profile of cohort 1, 2 and 3), this group will receive the Maximum Tolerated Dose (MTD).
DCP-001 vaccine is presented as a direct injectable sterile cell suspension consisting of
irradiated mature dendritic cells in cryopreservation solution packed in vials. The vaccine
will be administered intradermally.
Inclusion Criteria:
- Patients with AML, in second complete remission of AML (all FAB-subclasses), not
eligible for additional intensification therapies e.g. allogeneic (allo) PSCT
[independent of age]; OR
- Patients with relapse (smouldering) AML not eligible for additional intensification
therapies e.g. alloPSCT; OR
- Patients with de novo (smouldering) AML not eligible for intensive treatment
according to current HOVON trials.
- Patients >65 years of age with de novo AML in first CR and off protocol of current
HOVON trials.
- WHO performance of 0, 1, or 2.
- Male or female patients at least 18 years of age and <80 years by date of enrolment.
- Patients not treated within current HOVON or other AML trials.
- Ability and willingness to give informed consent.
- HLA-A2.1 positive patients (only for cohort 4).
Exclusion Criteria:
- Uncontrolled active infection.
- Previous immunotherapy in last 3 months (except for anti-CD33 targeted therapy).
- Previous allogeneic PSCT.
- Inadequate bone marrow function: absolute neutrophile count (ANC) < 0.5x10E9/L, or
platelet count < 20x10E9/L or active bleeding with platelet count > 20x10E9/L.
- Inadequate liver function, defined as:
- Serum (total) bilirubin > 1.5 x the upper limit of normal (ULN)
- AST/SGOT or ALT/SGPT > 2.5 x ULN
- Alkaline phosphatase levels > 2.5 times the ULN at baseline.
- Inadequate renal function, defined as:
- Serum creatinine > 1.5 x ULN
- Other malignancy 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. Serum pregnancy test to be assessed within 7 days
prior to study treatment start, or within 14 days with a confirmatory urine pregnancy
test within 7 days prior to study treatment start.
- Women of childbearing potential (defined as < 2 years after last menstruation and not
surgically sterile) not using effective, non-hormonal means of contraception
(intrauterine contraceptive device, barrier method of contraception in conjunction
with spermicidal jelly).
- 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.
- Minor surgical procedures, within 24 hours prior to the first study treatment.
- Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm Hg) or
clinically significant (i.e. active) cardiovascular disease: cerebrovascular accident
(CVA) / stroke within ≤ 6 months prior to the first study treatment, unstable angina,
New York Heart Association (NYHA) Grade II or greater congestive heart failure (CHF),
or serious cardiac arrhythmia requiring medication.
- Known hypersensitivity to any of the study drugs or excipients.
- Evidence of an other medical condition (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.
- Eligibility for the HOVON-93 study (intensification program ± allogeneic stem cell
transplant).
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label
Outcome Measure:
Safety/Feasibility of DCP-001 vaccination
Outcome Description:
The primary endpoint of this study will be the safety and feasibility of DCP-001 vaccination in AML patients. Safety will be assessed by means of laboratory evalulations, lhysical examination, vital sign assessments and adverse events recording. Clinical efficacy is assessed by the presence of leukemic cells in blood and bonemarrow and physical examination at baseline, during and after vaccination
Outcome Time Frame:
three months and follow up after study completion
Safety Issue:
Yes
Authority:
The Netherlands: Central Committee on Research involving Human Subjects
Study ID:
DCOne-1
NCT ID:
NCT01373515
Start Date:
April 2011
Completion Date:
May 2013
Related Keywords:
- Acute Myeloid Leukemia (AML)
- Leukemic Dendritic Cell Vaccination
- DCOne
- DCP-001
- Second complete remission of AML
- Relapse AML
- Leukemia
- Leukemia, Myeloid, Acute
- Leukemia, Myeloid
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