SNS-301 Monotherapy in High Risk MDS and CMML

Myelodysplastic Syndromes Clinical Trial

Official title:

An Open-Label, Multi-Center Phase 2 Clinical Trial Evaluating SNS-301 in Patients With ASPH+ High Risk Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04217720
• Other study ID #: SNS-301-2-1
• Status: Withdrawn
• Phase: Phase 2
• Start date: April 1, 2020
• Est. completion date: January 1, 2023

Study information

• Verified date: August 2021
• Source: Sensei Biotherapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To evaluate safety, immunogenicity and anti-tumor responses of intradermally delivered SNS-301 in patients with ASPH+ high risk MDS and CMML.

Description:

This phase 2, open-label, multi-center trial to evaluate the safety, immunogenicity and preliminary clinical efficacy of intradermally-delivered SNS-301 delivered using the 3M® hollow microstructured transdermal system (hMTS) device in patients with ASPH+ high risk myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML). The trial population consists of high risk ≥ Intermediate Risk-3 (IR-3) MDS and CMML-2.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 1, 2023
• Est. primary completion date: January 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Signed informed consent.

2. Be 18 years of age or older.

3. Confirmed diagnosis of MDS or CMML.

4. Assessment of high-risk-MDS/CMML status defined as follows:

1. MDS: IPSS-R criteria for categorization = Intermediate Risk-3

2. CMML: WHO criteria for CMML-2 (peripheral blasts of 5% to 19%, and 10% to 19% bone marrow blasts and/or presence of Auer rods).

5. Be willing to provide a fresh bone marrow aspirate sample at pre-treatment and demonstrate ASPH expression by flow cytometry.

6. Patient who has relapsed or is refractory / intolerant of hypomethylating agents (HMAs) or not responding to 4 treatment cycles of decitabine or 6 treatment cycles of azacytidine or progressing at any point after initiation of an HMA.

7. Patient refuses or is not considered a candidate for intensive induction chemotherapy using consensus criteria for defining such patients.

8. Patients with CMML must have been treated with at least 1 prior therapy (hydroxyurea or an HMA).

9. Eastern Cooperative Oncology Group (ECOG) Performance Scale 0-1.

10. Demonstrate adequate organ function: renal, hepatic, coagulation parameters.

11. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use two highly effective contraceptive methods during the treatment period and for at least 180 days after the last dose of study treatment. For male patients: Agree that during the period specified above, men will not father a child. Male patients must remain abstinent, must be surgically sterile during the treatment period and for at least 180 days after the last dose of study treatment.

Exclusion Criteria:

1. Any approved anti-cancer therapy including chemotherapy, targeted small molecule therapy or radiation therapy within 2 weeks prior to trial Day 0.

2. Participated on a clinical trial of an investigational agent and/or investigational device within 28 days prior to Day 0.

3. Malignancies other than indications open for enrollment within 3 years prior to Day 0.

4. Diagnosis of a core binding factor leukemia (t(8;21), t(16;16); or inv(16)) or diagnosis of acute promyelocytic leukemia (t(15;17)).

5. Active or history of autoimmune disease or immune deficiency.

6. History of HIV. HIV antibody testing recommended per investigator's clinical suspicion.

7. Active hepatitis B (hepatitis B surface antigen reactive) or active hepatitis C (HCV qualitative RNA detected); testing recommended per investigator's clinical suspicion.

8. Severe infections within 4 weeks prior to enrollment.

9. Received therapeutic oral or IV antibiotics within 2 weeks prior to Day 0.

10. History or current evidence of any condition, therapy or laboratory abnormality that in the opinion of the treating investigator might confound the results of the trial.

11. Known previous or ongoing, active psychiatric or substance abuse disorders that would interfere with the requirements of the trial.

12. Treatment with systemic immunomodulating agents (including but not limited to IFNs, IL-2) within 6 weeks or five half-lives of the drug, whichever is shorter, prior to first dose.

13. Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study.

Related Conditions & MeSH terms

• Chronic Myelomonocytic Leukemia (CMML)
• Leukemia
• Leukemia, Myelomonocytic, Chronic
• Leukemia, Myelomonocytic, Juvenile
• Myelodysplastic Syndromes
• Preleukemia

Intervention

Drug:
• SNS-301
SNS-301 (1x 1011 dose/1ml) ID injection every 3 weeks for 4 doses then every 6 weeks for 6 additional doses, and thereafter every 12 weeks up to 24 months.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Sensei Biotherapeutics, Inc.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events of SNS-301	Number of adverse events including adverse events of special interest as assessed by CTCAE v5.0	12 weeks
Primary	Objective response rate by International Working Group (IWG) 2006 criteria	Best objective response during the study	12 weeks
Primary	Minimal residual disease by IWG 2006 criteria	Minimal residual disease by peripheral and bone marrow blast count during the study	12 weeks
Primary	Duration of Response by IWG 2006 criteria	Duration of response calculated from date of first response to date of progression	12 weeks
Primary	Disease control rate (DCR) by IWG 2006 criteria	Disease control rate calculated as the proportion of patients with stable disease or better	12 weeks
Primary	Progression Free Survival (PFS) as assessed by IWG 2006 criteria	Progression free survival calculated from the date of start of treatment to date of progression	12 weeks
Primary	Overall Survival	Overall survival calculated from date of treatment to date of death	36 months
Secondary	Measurement of ASPH specific responses	Evaluate blood and tissue ASPH-specific responses at pretreatment, changes during treatment and at progression or end of study in all study participants where sample is available for analysis	up to 12 weeks
Secondary	Measurement of T cell immune response	Characterize blood and bone marrow T cell types and numbers at pretreatment, changes during treatment and at progression or end of study in all study participants where sample is available for analysis	up 12 weeks
Secondary	Measurement B cell immune responses	Characterize blood and bone marrow B cell numbers at pretreatment, changes during treatment and at progression or end of study in all study participants where sample is available for analyses	up to 12 weeks
Secondary	Evaluation of immune gene transcript profiles	Determine changes in commercially available gene signature panels in blood and bone marrow pretreatment, during treatment and at progression in all study participants where sample is available for analysis	up to12 weeks
Secondary	Measurement of pro-inflammatory and/or immunosuppressive molecules	The immunological response of pro-inflammatory/immunosuppressive molecules will be observed before, during and after treatment using commercially available assays. Analyses will be performed both on blood and bone marrow samples in all study participants where sample is available for analysis	up to 12 weeks
Secondary	Measurement of oncoprotein expression	Changes in oncoprotein levels will be evaluated before, during and after treatment using methods such as flow cytometry. Analyses will be performed both on blood and bone marrow samples in all study participants where sample is available for analysis	up to 12 weeks