Back to resultsLeukemic Dendritic Cell Vaccination in Patients With Acute Myeloid Leukemia
Primary Purpose
Acute Myeloid Leukemia (AML), Leukemic Dendritic Cell Vaccination
Status
Completed
Phase
Phase 1
Locations
Netherlands
Study Type
Interventional
Intervention
DCP-001
Sponsored by
About this trial
This is an interventional other trial for Acute Myeloid Leukemia (AML) focused on measuring DCOne, DCP-001, Second complete remission of AML, Relapse AML
Eligibility Criteria
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).
Sites / Locations
- VU University Medical Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Cohort 1; 1x10E7 DCP-001
Cohort 2; 2.5x10E7 DCP-001
Cohort 3; 5x10E7 DCP-001
Cohort 4; 5x10E7 DCP-001
Arm Description
n=3; patients receiving 4 bi-weekly vaccinations of 1x10E7 DCP-001.
n=3; patients receiving 4 bi-weekly vaccinations of 2.5x10E7 DCP-001.
n=3; patients receiving 4 bi-weekly vaccinations of 5x10E7 DCP-001.
n=3; patients, matched for HLA-A2, receiving 4 bi-weekly vaccinations of 5x10E7 DCP-001. Or, in case this turned out toxic, this group will receive the Maximum Tolerated Dose.
Outcomes
Primary Outcome Measures
Safety/Feasibility of DCP-001 vaccination
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
Secondary Outcome Measures
Immunological responses induced by DCP-001 vaccination
The secondary endpoint of this study will be establishment of immunological responses induced by DCP-001 vaccination.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01373515
Brief Title
Leukemic Dendritic Cell Vaccination in Patients With Acute Myeloid Leukemia
Official Title
Phase 1 Study of Leukemic Dendritic Cell Vaccination in Patients With Acute Myeloid Leukemia
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
April 2011 (undefined)
Primary Completion Date
February 2013 (Actual)
Study Completion Date
May 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mendus
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is an open label phase 1 feasibility and safety dose escalation study. The main objective is to evaluate the safety of DCP-001 intradermal vaccination in patients with AML.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia (AML), Leukemic Dendritic Cell Vaccination
Keywords
DCOne, DCP-001, Second complete remission of AML, Relapse AML
7. Study Design
Primary Purpose
Other
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1; 1x10E7 DCP-001
Arm Type
Experimental
Arm Description
n=3; patients receiving 4 bi-weekly vaccinations of 1x10E7 DCP-001.
Arm Title
Cohort 2; 2.5x10E7 DCP-001
Arm Type
Experimental
Arm Description
n=3; patients receiving 4 bi-weekly vaccinations of 2.5x10E7 DCP-001.
Arm Title
Cohort 3; 5x10E7 DCP-001
Arm Type
Experimental
Arm Description
n=3; patients receiving 4 bi-weekly vaccinations of 5x10E7 DCP-001.
Arm Title
Cohort 4; 5x10E7 DCP-001
Arm Type
Experimental
Arm Description
n=3; patients, matched for HLA-A2, receiving 4 bi-weekly vaccinations of 5x10E7 DCP-001. Or, in case this turned out toxic, this group will receive the Maximum Tolerated Dose.
Intervention Type
Biological
Intervention Name(s)
DCP-001
Intervention Description
4 bi-weekly vaccinations
Primary Outcome Measure Information:
Title
Safety/Feasibility of DCP-001 vaccination
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
Time Frame
three months and follow up after study completion
Secondary Outcome Measure Information:
Title
Immunological responses induced by DCP-001 vaccination
Description
The secondary endpoint of this study will be establishment of immunological responses induced by DCP-001 vaccination.
Time Frame
3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Facility Information:
Facility Name
VU University Medical Center
City
Amsterdam
Country
Netherlands
12. IPD Sharing Statement
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Leukemic Dendritic Cell Vaccination in Patients With Acute Myeloid Leukemia
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