Monoclonal GammopathyEarly Phase 1NCT03591614
Dendritic Cell DKK1 Vaccine for Monoclonal Gammopathy and Stable or Smoldering Myeloma
A Early Phase 1 study testing DKK1 in people with Monoclonal Gammopathy and Smoldering Myeloma, run by Case Comprehensive Cancer Center at 2 sites in United States.
Trial summary
The purpose of this study is to study the safety and preliminary efficacy of a dendritic cell DKK1 vaccine against myeloma. Dendritic cells are immune cells that are collected from the blood of the patient at Case Western Reserve Medical Center and then brought into contact with DKK1, a molecule that is present of… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Monoclonal Gammopathy, Smoldering Myeloma, Myeloma
- What is being tested?
- DKK1
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Dec 2023to 1 Aug 2025
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- At any time prior to enrollment subjects must have IgG, IgA, kappa, or lambda monoclonal gammopathy confirmed in at least two assessments at least three months apart or histologically confirmed multiple myeloma or carry a diagnosis of smoldering myeloma based on prior documentation of serum m-spike (IgG or IgA) of at least 3g/dL serum m-spike (IgG or IgA) or 24h urine m-spike of at least 500mg/24h.
- Within 28 days prior to enrollment persistence of the clonal plasma cell disorder must be documented by presence of a clonal band on immunofixation of blood or urine or an abnormal serum free kappa/lambda ratio.
- Subjects with myeloma related organ dysfunction must have received prior therapy, reached at least partial remission with at least one of any number of prior regimens, and be candidates for observation off myeloma therapy based on lack of progression at least stable disease for at least 90 days prior to at study entry.
- Performance status ECOG performance status ≤ 2.
- Subjects must have laboratory test results within the following ranges:
- Hemoglobin ≥ 9.0 g/dl
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- Absolute neutrophil count ≥ 1,500/mcL
- Platelet count ≥ 100,000/mcL
- Total bilirubin < 2.5 x institutional upper limit of normal
- AST (SGOT) ≤ 2.5 X institutional upper limit of normal
- ALT (SGPT) ≤ 2.5 X institutional upper limit of normal
- Calculated creatinine clearance (Cockcroft-Gault) ≥ 30ml/min
- Anti-myeloma treatment with proteasome inhibitors, IMiDsTM, corticosteroids, low dose cyclophosphamide (≤ 50mg per day) must have been discontinued at least 14 days prior to study entry. Conventional chemotherapy at conventional doses including cyclophosphamide at > 50mg per day must have been discontinued at least 28 days prior to study entry. At least 180 days must have passed since high dose chemotherapy used in the context of autologous stem cell transplantation. Prior radiation must have been completed at least 14 days prior to enrollment.
- Subjects must have the ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Subjects receiving any other investigational agents.
- Concurrent use of any plasma cell directed therapy including corticosteroids (use of bisphosphonates is allowed).
- Subjects who have previously received an allogeneic stem cell transplant.
- Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection (including active HIV or hepatitis), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Women with childbearing potential (last menstrual period within less than 24 months unless hysterectomy or bilateral oophorectomy has been performed since) as well as pregnant women are excluded from this study because DKK1 is expressed in placental tissue and a DKK1 immune response could harm the child. Breastfeeding women are excluded from this study because antibodies made in response to the dendritic cell DKK1 vaccine could enter milk and affect the health of the breastfed child.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, 44106
Cleveland Clinic, Case Comprehensive Cancer Center
Cleveland, Ohio, 44195
About this study
Official title: A Pilot Study of Dendritic Cell DKK1 Vaccine for Patients With Monoclonal Gammopathy and Stable or Smoldering Myeloma
The purpose of this study is to study the safety and preliminary efficacy of a dendritic cell DKK1 vaccine against myeloma. Dendritic cells are immune cells that are collected from the blood of the patient at Case Western Reserve Medical Center and then brought into contact with DKK1, a molecule that is present of myeloma cells but not to a significant amount on other cells except for the prostate and the placenta. It is an investigational (experimental) vaccine that based on studies in the laboratory and in mice is expected to work by presentation of DKK1 to anticancer immune cells via dendritic cells leading to an immune attack on myeloma cells. It is experimental because it is not approved by the Food and Drug Administration (FDA).
Read the detailed description
The overall objective of this pilot study is to determine the safety and preliminary efficacy of a dendritic cell DKK1 vaccine in view of possible future use as a strategy to prevent progression of asymptomatic plasma cell disorders, maintain disease control, and ultimately contribute to eradication of multiple myeloma, light and heavy chain amyloidosis, immunoglobulin deposition disease, and other malignant and non-malignant diseases related to transformed plasma cells.
Primary Objective Confirm the safety of dendritic cell DKK1 vaccine given every two weeks for three doses in patients with monoclonal gammopathy, stable or smoldering myeloma.
Secondary Objectives
- Assess response according to international response criteria (> partial response, PR) and clinical benefit response (>minor response, MR, according to adapted EBMT criteria)
- Determine time to progression
- Describe progression-free and overall survival
Correlative Objectives
- Explore correlation between myeloma DKK1 and PDL-1 expression and response
- Determine cellular immune response
- Assess serologic anti-DKK1 antibody response
Study design including dose escalation / cohorts Pilot study with 3 patient safety run-in, possible dose level -1 (DL-1) if dose limiting toxicity occurs in one or more patients at the target dose level, and, at the first dose level where no dose limiting toxicity occurs, extension by 12 patients.
DLT will be defined as any vaccine related toxicity > grade 3 that does not resolve to grade < 2 within 7 days. If any DLT occurs at DL-1 enrollment will be stopped and an amendment will be discussed.
- Conditions
- Monoclonal Gammopathy, Smoldering Myeloma, Myeloma
- Being tested
- DKK1
- Keywords
- Vaccine, DKK1
- Medical subject headings
- Paraproteinemias, Smoldering Multiple Myeloma, Neoplasms, Plasma Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DKK1Biological
The investigational agent is a DKK1 peptide-loaded autologous dendritic cell vaccine dispensed at a dose of 5-10x106 in 0.5 mL Plasma-Lyte A + 5% HSA.
| Study group | Role | What they receive |
|---|---|---|
| Dendritic cell DKK1 vaccine | Experimental | 5-10x106 DKK1 loaded dendritic cells. Three doses will be given two weeks apart, followed by 11 months of observations. Receives: Biological: DKK1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with dose limiting toxicity
Toxicity will be assessed according to CTCAE v.4.03. Patients will have weekly CBC w. Differential, CMP, history, and physical. DLT will be defined as any vaccine related non-hematologic toxicity, neutropenia, anemia or thrombocytopenia > grade 3 that does not resolve to grade < 2 within 7 days.
Measured: Up to 1 year
Secondary outcomes (5)
Average time of progression-free survival
Progression-free survival will be measured from administration of the first vaccine dose to progression as defined by updated uniform international response criteria or death of any cause, whichever comes first.
Measured: Up to 1 year
Average time of overall survival
Overall survival will be measured from administration of the first vaccine dose to death from any cause.
Measured: Up to 1 year
Average time to progression
Time to progression will be measured from administration of the first vaccine dose to progression as defined by updated uniform international response criteria
Measured: Up to 1 year
Best overall response
Response will be evaluated according to updated uniform response criteria
Measured: Up to 1 year
Clinical Benefit Response
Response will be evaluated according to updated uniform response criteria
Measured: Up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2018
- Study start1 Dec 2023 (estimated)
- Primary completion1 Aug 2024 (estimated)
- Study completion1 Aug 2025 (estimated)
Why it stopped: PI left institution
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Monoclonal GammopathyStudies of the same condition, open and under way.
- More trials run by Case Comprehensive Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Case Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ehsan Malek, MD, Principal investigator, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03591614
- Sponsor's protocol ID
- CASE1A16
- Status last verified
- Aug 2023
- First submitted
- 9 Jul 2018
- Last updated
- 18 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Dendritic Cell DKK1 Vaccine for Patients With Monoclonal Gammopathy and Stable or Smoldering Myeloma
- ClinicalTrials.gov ID
- NCT03591614
- Acronym / sponsor ID
- CASE1A16
- Conditions
- Monoclonal Gammopathy, Smoldering Myeloma, Myeloma
- Keywords
- Vaccine, DKK1
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: PI left institution
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Case Comprehensive Cancer CenterUniversity, hospital or other
- Study start
- 1 Dec 2023 (estimated)
- Primary completion
- 1 Aug 2024 (estimated)
- Study completion
- 1 Aug 2025 (estimated)
- First posted
- 19 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to study the safety and preliminary efficacy of a dendritic cell DKK1 vaccine against myeloma. Dendritic cells are immune cells that are collected from the blood of the patient at Case Western Reserve Medical Center and then brought into contact with DKK1, a molecule that is present of myeloma cells but not to a significant amount on other cells except for the prostate and the placenta. It is an investigational (experimental) vaccine that based on studies in the laboratory and in mice is expected to work by presentation of DKK1 to anticancer immune cells via dendritic cells leading to an immune attack on myeloma cells. It is experimental because it is not approved by the Food and Drug Administration (FDA).
Detailed description
The overall objective of this pilot study is to determine the safety and preliminary efficacy of a dendritic cell DKK1 vaccine in view of possible future use as a strategy to prevent progression of asymptomatic plasma cell disorders, maintain disease control, and ultimately contribute to eradication of multiple myeloma, light and heavy chain amyloidosis, immunoglobulin deposition disease, and other malignant and non-malignant diseases related to transformed plasma cells.
Primary Objective Confirm the safety of dendritic cell DKK1 vaccine given every two weeks for three doses in patients with monoclonal gammopathy, stable or smoldering myeloma.
Secondary Objectives
- Assess response according to international response criteria (> partial response, PR) and clinical benefit response (>minor response, MR, according to adapted EBMT criteria)
- Determine time to progression
- Describe progression-free and overall survival
Correlative Objectives
- Explore correlation between myeloma DKK1 and PDL-1 expression and response
- Determine cellular immune response
- Assess serologic anti-DKK1 antibody response
Study design including dose escalation / cohorts Pilot study with 3 patient safety run-in, possible dose level -1 (DL-1) if dose limiting toxicity occurs in one or more patients at the target dose level, and, at the first dose level where no dose limiting toxicity occurs, extension by 12 patients.
DLT will be defined as any vaccine related toxicity > grade 3 that does not resolve to grade < 2 within 7 days. If any DLT occurs at DL-1 enrollment will be stopped and an amendment will be discussed.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dendritic cell DKK1 vaccine | Experimental | Biological: DKK15-10x106 DKK1 loaded dendritic cells. Three doses will be given two weeks apart, followed by 11 months of observations. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- At any time prior to enrollment subjects must have IgG, IgA, kappa, or lambda monoclonal gammopathy confirmed in at least two assessments at least three months apart or histologically confirmed multiple myeloma or carry a diagnosis of smoldering myeloma based on prior documentation of serum m-spike (IgG or IgA) of at least 3g/dL serum m-spike (IgG or IgA) or 24h urine m-spike of at least 500mg/24h.
- Within 28 days prior to enrollment persistence of the clonal plasma cell disorder must be documented by presence of a clonal band on immunofixation of blood or urine or an abnormal serum free kappa/lambda ratio.
- Subjects with myeloma related organ dysfunction must have received prior therapy, reached at least partial remission with at least one of any number of prior regimens, and be candidates for observation off myeloma therapy based on lack of progression at least stable disease for at least 90 days prior to at study entry.
- Performance status ECOG performance status ≤ 2.
- Subjects must have laboratory test results within the following ranges:
Key exclusion criteria (5 listed)
- Subjects receiving any other investigational agents.
- Concurrent use of any plasma cell directed therapy including corticosteroids (use of bisphosphonates is allowed).
- Subjects who have previously received an allogeneic stem cell transplant.
- Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection (including active HIV or hepatitis), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Women with childbearing potential (last menstrual period within less than 24 months unless hysterectomy or bilateral oophorectomy has been performed since) as well as pregnant women are excluded from this study because DKK1 is expressed in placental tissue and a DKK1 immune response could harm the child. Breastfeeding women are excluded from this study because antibodies made in response to the dendritic cell DKK1 vaccine could enter milk and affect the health of the breastfed child.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DKK1The investigational agent is a DKK1 peptide-loaded autologous dendritic cell vaccine dispensed at a dose of 5-10x106 in 0.5 mL Plasma-Lyte A + 5% HSA. | Biological | Dendritic cell DKK1 vaccine |
Primary outcome
Number of patients with dose limiting toxicity
Time frame: Up to 1 year
Toxicity will be assessed according to CTCAE v.4.03. Patients will have weekly CBC w. Differential, CMP, history, and physical. DLT will be defined as any vaccine related non-hematologic toxicity, neutropenia, anemia or thrombocytopenia > grade 3 that does not resolve to grade < 2 within 7 days.
5 secondary outcomes
Average time of progression-free survival
Time frame: Up to 1 year
Average time of overall survival
Time frame: Up to 1 year
Average time to progression
Time frame: Up to 1 year
Best overall response
Time frame: Up to 1 year
Clinical Benefit Response
Time frame: Up to 1 year
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ehsan Malek, MD principal investigator
University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing DKK1 in people with Monoclonal Gammopathy and Smoldering Myeloma, run by Case Comprehensive Cancer Center at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 18 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients with dose limiting toxicity (time frame: Up to 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2023.