Clinical trial NCT05321940: Safety Trial of STING-dependent Activators and Stimulated Dendritic Cells for Aggressive Relapsed/Refractory Leukemias
Official title: A Pilot Safety Trial of STING-dependent Activators (STAVs) and Stimulated Dendritic Cells for Aggressive Relapsed/Refractory Leukemias
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Refractory Leukemia
Relapsed Leukemia
Acute Myelogenous Leukemia
Acute Lymphoblastic Leukemia
Adult T-Cell Leukemia/Lymphoma
Lead sponsor: University of Miami
Sponsor class: OTHER
First posted: 2022-04-11
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: Inclusion Criteria:

1. 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).
2. 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.
3. 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
   * 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.
4. Adults (≥ 18 years of age) regardless of their gender and genetic background
5. Karnofsky performance status (KPS) ≥ 50% or Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3. (see Appendix B for definitions).
6. Must have adequate end organ and bone marrow function as defined below:
7. Absolute neutrophil count (ANC)≥ 1,000 cells/mm3 (Exception: Unless cytopenias are secondary to leukemia disease).
8. Platelets (PLT) ≥ 50,000 cells/mm3 (Exception: Unless cytopenias are secondary to leukemia).
9. 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).
10. 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
11. Patients receiving erythropoietin or granulocyte colony-stimulating factor (G-CSF) from baseline are eligible.
12. 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.

Exclusion Criteria:

1. Patients who have previously received allogeneic stem cell transplant are ineligible
2. Patients receiving cytotoxic chemotherapy within 14 days or any other investigational biological agents within 7 days prior to initiation of study therapy.
3. Any concomitant participation in other therapeutic trials.
4. 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.
5. HIV infection.
6. Active or latent syphilis.
7. 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.
8. Patients with known central nervous system (CNS) involvement.
9. Pregnant or breast-feeding women.
10. 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.
11. Known New York Heart Association (NYHA) Class 3 or 4 heart disease as per Appendix C.
12. Known history of cardiomyopathy with ejection fraction \< 45% (or lower limit of institutional normal value) or uncontrolled arrhythmia.
13. Psychological, familial, sociological or geographical conditions likely in the judgment of the Investigator(s) to interfere or limit compliance with study requirements/treatment
14. Known active deep venous thrombosis (DVT) or pulmonary embolism

Primary outcomes:
measure: Incidence of Treatment-Related Adverse events
timeFrame: Up to 12 months
Secondary outcomes:
measure: Percentage of Participants Achieving Clinical Overall Response (OR)
timeFrame: Up to 12 months
measure: Percentage of Participants Achieving Clinical Complete Response (CR)
timeFrame: Up to 12 months
measure: Percentage of Participants with AML Achieving Clinical Complete Response rate with Incomplete Hematologic Recovery (CRi)
timeFrame: Up to 12 months
measure: Percentage of Participants with Minimal Residual Disease (MRD)
timeFrame: Up to 12 months
measure: Percentage of Participants Achieving Molecular Complete Response (MCR)
timeFrame: Up to 12 months
measure: Failure-free survival (FFS) rate
timeFrame: Up to 1 year
measure: Overall survival (OS)
timeFrame: Up to 1 year
Other outcomes:
Locations:
Study officials:
affiliation: University of Miami
name: Juan C Ramos, MD
role: PRINCIPAL_INVESTIGATOR
References: