Refractory LeukemiaPhase 1NCT05321940
Safety Trial of STING-dependent Activators and Stimulated Dendritic Cells for Aggressive Relapsed/Refractory Leukemias
A Phase 1 study testing STING-Dependent Activators (STAVs) Loaded Autologous Leukemic Cells and Dendritic Cell Vaccine in people with Refractory Leukemia and Relapsed Leukemia, run by Juan C. Ramos, MD.
Trial summary
The purpose of this research is to investigate whether the combination of STING-dependent Adjuvants (STAVs) and dendritic cell (DC) vaccine therapies will increase the body's ability to fight aggressive relapsed or refractory leukemias. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Refractory Leukemia, Relapsed Leukemia, Acute Myelogenous Leukemia
- What is being tested?
- STING-Dependent Activators (STAVs) Loaded Autologous Leukemic Cells and Dendritic Cell Vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 30 Nov 2023to 30 Nov 2026
- Phase
- 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
- Histologically or cytologically documented adult T-cell leukemia/lymphoma (ATLL), Cluster of Differentiation (CD)34+ acute myelogenous leukemia (AML), or acute lymphoblastic leukemia (B-cell or T-cell ALL). Eligible patients with ATLL must have leukemic involvement (See Appendix K for subtype classification).
- Must have evidence of persistent refractory disease or progression at the time of screening and documented presence of leukemic cells in peripheral blood by either morphology, histology, or flow cytometry.
- Must have failed standard induction and salvage therapies available AND be ineligible for allogeneic stem cell transplant ǂ as follows:
- For ATLL, must not have failed standard combination chemotherapy (i.e. doxorubicin or etoposide based regimen), salvage chemotherapy (i.e. ifosfamide + carboplatin + etoposide (ICE), dexamethasone, High-dose Cytarabine (Ara-C) and cisplatin (DHAP), or gemcitabine + oxaliplatin (GEMOX)), brentuximab vedotin if CD30+, interferon based therapy if acute or chronic type, and mogamulizumab provided patient is a suitable candidate for the above therapies ±.
- Relapsed/refractory (R/R) AML is defined as patients ≥ 18 years of age at the time of signing the informed consent form (ICF) who are not eligible to receive further intensive therapy and:
- Have failed to achieve a complete remission (CR) or morphologic complete remission with incomplete blood count recovery (CRi) after induction plus reinduction with intensive chemotherapy (e.g., anthracycline plus cytarabine or high-dose cytarabine containing regimens) if a suitable candidateǂ or 4 cycles of low-intensity therapy (i.e. azacytidine, or decitabine based regimens) (either 4 cycles of the same regimen or a combination of 2 different regimens) OR
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- Have relapsed from CR or CRi from either intensive or low-intensity therapy. Subjects with second or multiple relapses are also eligible.
- For R/R ALL, the patient must have failed (relapsed or primary refractory) induction chemotherapy with consolidation if a suitable candidate± (i.e. ECOG 2993 or similar regimen). The patient should also have failed blinatumomab if CD19+ B-cell ALL, inotuzumab if CD22+ B-cell ALL, tyrosine kinase inhibitor if bcr-abl+, or salvage chemotherapy if available and if the patient is a suitable candidate± for these therapies.
- ± A suitable candidate is defined by a patient who has no contraindications to the available chemotherapy based on organ function, age, and overall health and performance status as determined by the treating physician.
- ǂ Transplant ineligible patients are defined as those not suitable for potentially curative allogeneic stem cell transplant based on lack of disease control or remission at the time of evaluation, inadequate organ function, age, and overall health and performance status as determined by the treating physician, or patient's refusal to undergo such treatment procedure.
- Adults (≥ 18 years of age) regardless of their gender and genetic background
- Karnofsky performance status (KPS) ≥ 50% or Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3. (see Appendix B for definitions).
- Must have adequate end organ and bone marrow function as defined below:
- Absolute neutrophil count (ANC)≥ 1,000 cells/mm3 (Exception: Unless cytopenias are secondary to leukemia disease).
- Platelets (PLT) ≥ 50,000 cells/mm3 (Exception: Unless cytopenias are secondary to leukemia).
- Hepatic function: transaminase ≤ 2.5 x the institutional upper limit of normal, total bilirubin ≤ 1.5 x institutional upper limit of normal, (Exception: Unless secondary to hepatic infiltration with leukemia).
- Females of childbearing potential (CBP) must have a negative pregnancy test within one week of enrollment. Women should avoid pregnancy while receiving study treatment. Males and females must agree to use adequate methods of birth control during participation in this trial and for 3 months after completing therapy
- Patients receiving erythropoietin or granulocyte colony-stimulating factor (G-CSF) from baseline are eligible.
- Ability to understand and willingness to sign a written informed consent document. Written consent by patient or legal guardian on an institutional review board (IRB)-approved informed consent form prior to any study-specific evaluation. Subject or legal guardian must be capable of understanding the investigational nature, potential risks and benefits of the study and able to provide valid informed consent.
Who cannot join
- Patients who have previously received allogeneic stem cell transplant are ineligible
- Patients receiving cytotoxic chemotherapy within 14 days or any other investigational biological agents within 7 days prior to initiation of study therapy.
- Any concomitant participation in other therapeutic trials.
- All patients will be required to be screened for Hepatitis B and C. Patients with active hepatitis B (HBsAg+ and Immunoglobulin M (IgM)+ for Hepatitis B core antigen) will not be eligible for trial enrollment. Those found to be Immunoglobulin G (IgG)+ for Hepatitis core antigen only may be eligible as long as they are receiving anti-Hepatitis B prophylactic therapy and liver function tests meet criteria listed under 4.1.10 above, and have no evidence of cirrhosis. The exact Hepatitis B therapy will be at the discretion of the infection disease specialist or investigator. Participants who are Hepatitis C antibody positive without a positive Hepatitis C RNA level, will be permitted to enroll in the study provided liver function tests meet criteria listed under 4.1.10 above, and have no evidence of cirrhosis on imaging.
- HIV infection.
- Active or latent syphilis.
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- Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (CHF), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that are likely in the judgment of the Investigator(s) to interfere or limit compliance with study requirements/treatment.
- Patients with known central nervous system (CNS) involvement.
- Pregnant or breast-feeding women.
- Concurrent active malignancies, with the exception of in situ carcinoma of the cervix, non-metastatic, non- melanomatous skin cancer, or Kaposi's sarcoma not requiring systemic chemotherapy.
- Known New York Heart Association (NYHA) Class 3 or 4 heart disease as per Appendix C.
- Known history of cardiomyopathy with ejection fraction < 45% (or lower limit of institutional normal value) or uncontrolled arrhythmia.
- Psychological, familial, sociological or geographical conditions likely in the judgment of the Investigator(s) to interfere or limit compliance with study requirements/treatment
- Known active deep venous thrombosis (DVT) or pulmonary embolism
About this study
Official title: A Pilot Safety Trial of STING-dependent Activators (STAVs) and Stimulated Dendritic Cells for Aggressive Relapsed/Refractory Leukemias
The purpose of this research is to investigate whether the combination of STING-dependent Adjuvants (STAVs) and dendritic cell (DC) vaccine therapies will increase the body's ability to fight aggressive relapsed or refractory leukemias.
- Conditions
- Refractory Leukemia, Relapsed Leukemia, Acute Myelogenous Leukemia, Acute Lymphoblastic Leukemia, Adult T-Cell Leukemia/Lymphoma
- Being tested
- STING-Dependent Activators (STAVs) Loaded Autologous Leukemic Cells, Dendritic Cell Vaccine
- Medical subject headings
- Leukemia, Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
STING-Dependent Activators (STAVs) Loaded Autologous Leukemic CellsBiological
Also called STING (Stimulator of Interferon Genes)-Dependent Activators, STAVs-Loaded Autologous Leukemic Cells, STING-dependent innate immune agonists
Autologous human ultraviolet (UV)-irradiated (dead) leukemia cells loaded with STAVs administered via intravenous injection. Each treatment will administer 5 ml via syringe.
Dendritic Cell VaccineBiological
Also called DC Vaccine
15-20 Million mature dendritic cells per dose administered via intravenous injection.
| Study group | Role | What they receive |
|---|---|---|
| Combination STAVs and DC Vaccine Group | Experimental | Participants will receive STAV-loaded cells for a total of 5 doses on Days 3, 17, 31, 45 and 59. Participants will also receive up to 4 doses of dendritic vaccine on Days 10, 17, 24 and 31. Receives: Biological: STING-Dependent Activators (STAVs) Loaded Autologous Leukemic Cells; Biological: Dendritic Cell Vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Related Adverse events
The incidence of treatment-limiting toxicities (TLTs) and treatment-related adverse events, including serious adverse events, in study participants will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, per physician discretion.
Measured: Up to 12 months
Secondary outcomes (7)
Percentage of Participants Achieving Clinical Overall Response (OR)
The percentage of participants achieving clinical overall response (complete response (CR) or partial response (PR)) as best response to protocol therapy will be reported. Response will be assessed on the basis of clinical, radiologic, molecular and pathologic (i.e. bone marrow) criteria.
Measured: Up to 12 months
Percentage of Participants Achieving Clinical Complete Response (CR)
The percentage of participants achieving clinical complete response (CR) as best response to protocol therapy will be reported. Response will be assessed on the basis of clinical, radiologic, molecular and pathologic (i.e. bone marrow) criteria.
Measured: Up to 12 months
Percentage of Participants with AML Achieving Clinical Complete Response rate with Incomplete Hematologic Recovery (CRi)
The percentage of participants with acute myelogenous leukemia (AML) achieving clinical complete response with incomplete hematologic recovery (CRi) as best response to protocol therapy will be reported. Response will be assessed on the basis of clinical, radiologic, molecular and pathologic (i.e. bone marrow) criteria.
Measured: Up to 12 months
Percentage of Participants with Minimal Residual Disease (MRD)
The percentage of participants with minimal residual disease after protocol therapy will be reported. Minimal residual disease (MRD) is defined as the persistence of malignant leukemic cells, as detected by conventional morphologic methods (flow cytometry, polymerase chain reaction (PCR), cytogenetics, fluorescence in situ hybridization (FISH), or next generation sequencing), among participants who meet clinical complete response (CR).
Measured: Up to 12 months
Percentage of Participants Achieving Molecular Complete Response (MCR)
The percentage of participants achieving molecular complete response (MCR) will b reported. MCR is defined as no evidence of disease at any body sites below the threshold of detection by conventional morphologic methods pertinent to each study disease (flow cytometry, PCR, T-cell receptor gene rearrangement, cytogenetics, FISH, or next generation sequencing).
Measured: Up to 12 months
Failure-free survival (FFS) rate
Failure-free survival (FFS) is defined as the time from study treatment initiation until documented disease progression, relapse after response, death (by any cause, in the absence of progression), or censoring. In the failure-free subjects, FFS will be censored at the last documented date of failure-free status. FFS rate will be reported as the percentage of participants without progressive disease after start of treatment.
Measured: Up to 1 year
Overall survival (OS)
Overall survival (OS) is defined as the elapsed time from study treatment initiation to death or date of censoring. Participants alive or those lost to follow-up will be censored at the last date known to be alive. OS rate will be reported as the percentage of participants still alive after start of treatment.
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 posted11 Apr 2022
- Study start30 Nov 2023 (estimated)
- Primary completion30 Nov 2025 (estimated)
- Study completion30 Nov 2026 (estimated)
Why it stopped: Investigator decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory LeukemiaStudies of the same condition, open and under way.
- 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
- 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
- Juan C. Ramos, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Juan C. Ramos, MD, University of Miami
- Investigators
- Juan C Ramos, MD, Principal investigator, University of Miami
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05321940
- Sponsor's protocol ID
- 20200982
- Status last verified
- Sep 2023
- First submitted
- 1 Apr 2022
- Last updated
- 4 Dec 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Safety Trial of STING-dependent Activators (STAVs) and Stimulated Dendritic Cells for Aggressive Relapsed/Refractory Leukemias
- ClinicalTrials.gov ID
- NCT05321940
- Acronym / sponsor ID
- 20200982
- Conditions
- Refractory Leukemia, Relapsed Leukemia, Acute Myelogenous Leukemia, Acute Lymphoblastic Leukemia, Adult T-Cell Leukemia/Lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Investigator decision
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Juan C. Ramos, MDUniversity, hospital or other
- Study start
- 30 Nov 2023 (estimated)
- Primary completion
- 30 Nov 2025 (estimated)
- Study completion
- 30 Nov 2026 (estimated)
- First posted
- 11 Apr 2022 (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 research is to investigate whether the combination of STING-dependent Adjuvants (STAVs) and dendritic cell (DC) vaccine therapies will increase the body's ability to fight aggressive relapsed or refractory leukemias.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Combination STAVs and DC Vaccine Group | Experimental | Biological: STING-Dependent Activators (STAVs) Loaded Autologous Leukemic Cells, Biological: Dendritic Cell VaccineParticipants will receive STAV-loaded cells for a total of 5 doses on Days 3, 17, 31, 45 and 59. Participants will also receive up to 4 doses of dendritic vaccine on Days 10, 17, 24 and 31. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Histologically or cytologically documented adult T-cell leukemia/lymphoma (ATLL), Cluster of Differentiation (CD)34+ acute myelogenous leukemia (AML), or acute lymphoblastic leukemia (B-cell or T-cell ALL). Eligible patients with ATLL must have leukemic involvement (See Appendix K for subtype classification).
- Must have evidence of persistent refractory disease or progression at the time of screening and documented presence of leukemic cells in peripheral blood by either morphology, histology, or flow cytometry.
- Must have failed standard induction and salvage therapies available AND be ineligible for allogeneic stem cell transplant ǂ as follows:
- For ATLL, must not have failed standard combination chemotherapy (i.e. doxorubicin or etoposide based regimen), salvage chemotherapy (i.e. ifosfamide + carboplatin + etoposide (ICE), dexamethasone, High-dose Cytarabine (Ara-C) and cisplatin (DHAP), or gemcitabine + oxaliplatin (GEMOX)), brentuximab vedotin if CD30+, interferon based therapy if acute or chronic type, and mogamulizumab provided patient is a suitable candidate for the above therapies ±.
- Relapsed/refractory (R/R) AML is defined as patients ≥ 18 years of age at the time of signing the informed consent form (ICF) who are not eligible to receive further intensive therapy and:
Key exclusion criteria (14 listed)
- Patients who have previously received allogeneic stem cell transplant are ineligible
- Patients receiving cytotoxic chemotherapy within 14 days or any other investigational biological agents within 7 days prior to initiation of study therapy.
- Any concomitant participation in other therapeutic trials.
- All patients will be required to be screened for Hepatitis B and C. Patients with active hepatitis B (HBsAg+ and Immunoglobulin M (IgM)+ for Hepatitis B core antigen) will not be eligible for trial enrollment. Those found to be Immunoglobulin G (IgG)+ for Hepatitis core antigen only may be eligible as long as they are receiving anti-Hepatitis B prophylactic therapy and liver function tests meet criteria listed under 4.1.10 above, and have no evidence of cirrhosis. The exact Hepatitis B therapy will be at the discretion of the infection disease specialist or investigator. Participants who are Hepatitis C antibody positive without a positive Hepatitis C RNA level, will be permitted to enroll in the study provided liver function tests meet criteria listed under 4.1.10 above, and have no evidence of cirrhosis on imaging.
- HIV infection.
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 |
|---|---|---|
| STING-Dependent Activators (STAVs) Loaded Autologous Leukemic CellsAlso: STING (Stimulator of Interferon Genes)-Dependent Activators, STAVs-Loaded Autologous Leukemic Cells, STING-dependent innate immune agonistsAutologous human ultraviolet (UV)-irradiated (dead) leukemia cells loaded with STAVs administered via intravenous injection. Each treatment will administer 5 ml via syringe. | Biological | Combination STAVs and DC Vaccine Group |
| Dendritic Cell VaccineAlso: DC Vaccine15-20 Million mature dendritic cells per dose administered via intravenous injection. | Biological | Combination STAVs and DC Vaccine Group |
Primary outcome
Incidence of Treatment-Related Adverse events
Time frame: Up to 12 months
The incidence of treatment-limiting toxicities (TLTs) and treatment-related adverse events, including serious adverse events, in study participants will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, per physician discretion.
7 secondary outcomes
Percentage of Participants Achieving Clinical Overall Response (OR)
Time frame: Up to 12 months
Percentage of Participants Achieving Clinical Complete Response (CR)
Time frame: Up to 12 months
Percentage of Participants with AML Achieving Clinical Complete Response rate with Incomplete Hematologic Recovery (CRi)
Time frame: Up to 12 months
Percentage of Participants with Minimal Residual Disease (MRD)
Time frame: Up to 12 months
Percentage of Participants Achieving Molecular Complete Response (MCR)
Time frame: Up to 12 months
Failure-free survival (FFS) rate
Time frame: Up to 1 year
Overall survival (OS)
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 4 Dec 2023.
- Individual participant dataSharing planned: No
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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.
Juan C Ramos, MD principal investigator
University of Miami
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing STING-Dependent Activators (STAVs) Loaded Autologous Leukemic Cells and Dendritic Cell Vaccine in people with Refractory Leukemia and Relapsed Leukemia, run by Juan C. Ramos, MD.
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 19 inclusion and 14 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 4 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
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?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Incidence of Treatment-Related Adverse events (time frame: Up to 12 months). 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 4 Dec 2023.