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Study of SIRPant-M in Participants With Relapsed or Refractory Non-Hodgkin's Lymphoma

Primary Purpose

Refractory Non-Hodgkin Lymphoma, Relapsed Non-Hodgkin Lymphoma

Status
Not yet recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
SIRPant-M
External-beam radiotherapy (XRT)
Sponsored by
SIRPant Immunotherapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Refractory Non-Hodgkin Lymphoma focused on measuring Non-Hodgkin Lymphoma, Relapsed/Refractory Non-Hodgkin Lymphoma, Autologous cell therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Adult, defined as age ≥ 18 (at screening), who are willing and able to provide informed consent Must have relapsed/refractory lymphoma, received at least 2 lines of systemic therapy, be ineligible or inappropriate for other treatment regimens known to have curative potential, and must have recovered from the acute toxic effects of all prior oncologic therapy of curative intent (except alopecia) Histologically or cytologically confirmed diagnosis of NHL, any one of the below: Eligible for SIRPant-M monotherapy or SIRPant-M plus focal XRT combination therapy: Diffuse large B-cell lymphoma and cutaneous T-cell lymphoma (CTCL), including mycosis fungoides (MF), Sezary Syndrome, anaplastic large cell lymphoma (ALCL), lymphomatoid papulosis; adult T-cell leukemia/lymphoma (ATLL); peripheral T cell lymphoma; and angioimmunoblastic T cell lymphoma Eligible for SIRPant-M monotherapy only: Cutaneous B-cell lymphoma, including primary cutaneous follicle center lymphoma and primary cutaneous marginal zone B-cell, leg type; follicular center lymphoma; chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL); mantle cell lymphoma (MCL); nodal marginal zone B-cell lymphoma Must have at least one accessible lymph node or cutaneous or subcutaneous lesion of 1.5 to 5 cm in one dimension as measured by computed tomography (CT) or positron emission tomography/computed tomography (PET/CT) or ultrasound for ITI by an interventional radiologist or other appropriately qualified and trained personnel, which presents a low risk for complications as determined by the Interventional Radiologist and the Principal Investigator. The target lesion must not have been previously irradiated. Note that lesions in the vicinity of large vessels, and tumor-encased large vessels are not considered low-risk. Additional caution should be taken in patients with neck lesions and lesions connected to ulcerated skin or mucosal surface. The target lesion must not be >5 cm in any dimension. Must have a life expectancy > 3 months; must also be confirmed within 7 days prior to Day 1 of SIRPant-M ITI treatment Must have an Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2; must also be confirmed within 7 days prior to Day 1 of SIRPant-M ITI treatment Must have hematologic values as follows: hemoglobin (Hgb) > 8 g/dL, ANC > 500 /mm3, monocyte counts ≥ 200/μL, and platelets > 50,000/µL; must also be confirmed within 7 days prior to Day 1 of SIRPant-M ITI treatment Must have adequate renal and hepatic function as follows: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <3× the upper limit of normal (ULN) (unless attributed to leukemic involvement or required concomitant medication) Calculated creatinine clearance ≥60 milliliter per minute (mL/min) calculated with Cockcroft-Gault formula Bilirubin ≤1.5×ULN, unless secondary to Gilbert's Syndrome. Must also be confirmed within 7 days prior to Day 1 of SIRPant-M ITI treatment. Cardiac function: Must be American Heart Association (AHA) class 1 without significant limitation of physical activity; must also be confirmed within 7 days prior to Day 1 of SIRPant-M ITI treatment. Must not be pregnant or planning to become pregnant. A negative urine or serum pregnancy test result is required for persons of reproductive potential within 72 hours prior to start of study treatment administration. All persons of reproductive potential must agree to use an effective contraceptive method during study participation and for a minimum of 90 days after study treatment. Biologically female: is premenarcheal, surgically sterile (post hysterectomy, bilateral salpingectomy, or bilateral oophorectomy), postmenopausal (>12 months of amenorrhea without alternative medical causes), or, if of reproductive potential, is using a highly effective method of contraception (combined estrogen/progestogen or progestogen-only hormonal contraceptives associated with inhibition of ovulation, intrauterine device [IUD], intrauterine hormone-releasing system [IUS], bilateral tubal occlusion/ligation, vasectomized partner[s], double barrier method [male condom with either cap, diaphragm, or sponge with spermicide], or true abstinence of heterosexual intercourse when this is in line with the preferred and usual lifestyle of the person [periodic abstinence, eg, calendar, ovulation, symptom-thermal, post-ovulation methods, and withdrawal are not acceptable methods of contraception]), and agrees to continued use of this method until 90 days after end of study treatment Biologically male: is vasectomized and has received medical assessment of surgical success, has undergone bilateral orchidectomy, or agrees to use an approved method of contraception (true abstinence of heterosexual intercourse when this is in line with the preferred and usual lifestyle of the person, double barrier method [male condom with either cap, diaphragm, or sponge with spermicide], partner's use of a highly effective method of contraception sterile, partner is postmenopausal, or partner is surgically sterile) and agrees to use this method until 90 days after study treatment In the opinion of the Investigator, must be willing and able to comply with the protocol for the duration of the study including undergoing treatment, the required tumor tissue biopsy procedures, scheduled visits and examinations, and including follow up Exclusion Criteria: Must not have received prior ITI therapy Must not have received ASCT or treatment with cellular therapy including CAR-T within the prior 1 month; must not have received allogeneic stem cell transplantation within prior 6 months and must have no active graft-versus-host disease (GVHD) or be under active immunosuppression for GVHD. Must not have received prior systemic anti-cancer therapy within the past 14 days before start of study cell therapy Must not have received IL-2 therapy within the last 6 months Must not have acquired immune defects such as human immunodeficiency virus (HIV) Must not have uncontrolled hypertension (systolic >180 mmHg, diastolic >100 mmHg) Must not have diagnosis of unclassifiable B cell lymphoma Must not have bleeding diathesis or abnormal values for prothrombin time (PT) or activated partial thromboplastin time (aPTT), international normalized ratio (INR) > 1.5× ULN Must not be receiving anti-platelet drugs that may present a risk for intratumor injections Must not have pulmonary disease which, in the opinion of the Investigator, might impair the patient's respiratory tolerance to moderate pulmonary fluid overload (eg, interstitial lung disease, severe chronic obstructive pulmonary disease) Must not have known alcohol or drug abuse Must not have received an investigational agent within the past 30 days before start of study cell therapy Must not require a chronic therapy with prednisone at a dose of or exceeding 10 mg/day or equivalent or any other form of immunosuppressive therapy Must not have active central nervous system tumors or metastases Must not be ineligible to receive 2.5 Gy ×3 focal external-beam radiation therapy as determined by the Radiation Oncologist and Principal Investigator (Cohort 1/Group 2, Cohort 2/Group 4, and Cohort -1/Group 4 only) Must not have uncontrolled active viral hepatitis-B, -C, and/or -D infection Must not have received a live vaccine within 4 weeks of the baseline/screening visit Must not have active, uncontrolled autoimmune disease and/or history of autoimmune diseases at high risk for relapse Must not have another malignancy or uncontrolled intercurrent illness, condition, serious medical or psychiatric illness, or circumstance that, in the opinion of the Investigator, could interfere with adherence to the study's procedures or requirements, or otherwise compromise the study's objectives No active systemic infection; must also be confirmed on Day 1 prior to initiation of ITI

Sites / Locations

  • City of Hope
  • Hackensack University Medical Center
  • MD Anderson Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

SIRPant-M (90×10^6 cells)

SIRPant-M (90×10^6 cells) coupled with focal XRT

SIRPant-M (300×10^6 cells)

SIRPant-M (300×10^6 cells) coupled with focal XRT

Arm Description

SIRPant-M Monotherapy

SIRPant-M coupled with 2.5 Gy of focal XRT administered within 24 hours after the first ITI and within 3 hours before to 24 hours after the second and third ITI

SIRPant-M Monotherapy

SIRPant-M coupled with 2.5 Gy of focal XRT administered within 24 hours after the first ITI and within 3 hours before to 24 hours after the second and third ITI

Outcomes

Primary Outcome Measures

Incidence of treatment emergent adverse events (TEAEs) and adverse events (AEs)
Includes evaluation of frequency and severity of AEs, serious adverse events (SAEs), TEAEs, and adverse events of special interest (AESIs), including injection site reactions and abnormalities in clinical laboratory assessments, vital signs, or physical examination findings. Graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.

Secondary Outcome Measures

Recommended phase 2 dose of autologous SIRPant-M +/- 2.5 Gy ×3 focal XRT
Based on review of safety, pharmacodynamic, and efficacy data.
Objective response rate (ORR)
Based on number of participants with complete response (CR) and partial response (PR). Determined by positron emission tomography/computed tomography (PET/CT) and evaluated per the Lugano classification.

Full Information

First Posted
July 21, 2023
Last Updated
September 8, 2023
Sponsor
SIRPant Immunotherapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05967416
Brief Title
Study of SIRPant-M in Participants With Relapsed or Refractory Non-Hodgkin's Lymphoma
Official Title
Phase 1, Open-Label Study of Autologous SIRPα-low Macrophages (SIRPant-M) Administered by Intratumoral Injection Alone or in Combination With Focal External-Beam Radiotherapy in Participants With Relapsed or Refractory Non-Hodgkin's Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
December 2023 (Anticipated)
Primary Completion Date
March 2025 (Anticipated)
Study Completion Date
March 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
SIRPant Immunotherapeutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The goal of this study is to test SIRPant-M, an autologous cell therapy, alone or in combination with focal external-beam radiotherapy in participants with relapsed or refractory non-Hodgkin's lymphoma (NHL). Two dose levels of SIRPant-M are being tested. The main question this study aims to answer is if SIRPant-M alone or in combination with radiotherapy is safe and well-tolerated.
Detailed Description
This is an open-label phase 1 study of SIRPant-M studied in serial cohorts either alone (monotherapy), or combined with low-dose focal external-beam radiotherapy (XRT) in patients with relapsed- or refractory Non-Hodgkin's lymphoma (NHL). Both B-cell and certain T-cell NHL (select PTCL; CTCL) are eligible. The primary objective of the study is to assess the safety and tolerability of autologous SIRPant-M, delivered by 3 intra-tumoral injection, given either alone or combined with 2.5 Gy focal XRT. A course (cycle) of SIRPant-M is prepared from a single mononuclear apheresis, and comprises 3 equal ITI doses, administered at 2-day intervals. A low dose (90x10^6 cells split over 3 injections) and a high dose (300x10^6 cells split over 3 injections) of SIRPant-M are evaluated. In cohorts receiving supplemental radiation, each cell injection will be followed by 2.5 Gy radiation directed at the injected tumor site (7.5 Gy total). Dose escalations will be staggered using the 3+3 Phase 1 design, and safety will be monitored by the Safety Review Committee (SRC). The SRC may direct additional- or intermediate dose levels to be evaluated, as guided by emerging data.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Refractory Non-Hodgkin Lymphoma, Relapsed Non-Hodgkin Lymphoma
Keywords
Non-Hodgkin Lymphoma, Relapsed/Refractory Non-Hodgkin Lymphoma, Autologous cell therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
Enrollment will begin with Cohort 1, Group 1 (SIRPant-M monotherapy, low dose). Upon approval from the SRC after Cohort 1, Group 1 review, enrollment in Cohort 1, Group 2 (SIRPant-M coupled with XRT, low dose) and Cohort 2, Group 3 (SIRPant-M monotherapy, high dose) will open. Upon approval from the SRC after Cohort 1, Group 2 and Cohort 2, Group 3 review, enrollment in Cohort 2, Group 4 (SIRPant-M coupled with XRT, high dose) will open.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
SIRPant-M (90×10^6 cells)
Arm Type
Experimental
Arm Description
SIRPant-M Monotherapy
Arm Title
SIRPant-M (90×10^6 cells) coupled with focal XRT
Arm Type
Experimental
Arm Description
SIRPant-M coupled with 2.5 Gy of focal XRT administered within 24 hours after the first ITI and within 3 hours before to 24 hours after the second and third ITI
Arm Title
SIRPant-M (300×10^6 cells)
Arm Type
Experimental
Arm Description
SIRPant-M Monotherapy
Arm Title
SIRPant-M (300×10^6 cells) coupled with focal XRT
Arm Type
Experimental
Arm Description
SIRPant-M coupled with 2.5 Gy of focal XRT administered within 24 hours after the first ITI and within 3 hours before to 24 hours after the second and third ITI
Intervention Type
Biological
Intervention Name(s)
SIRPant-M
Intervention Description
Autologous activated macrophage cell therapy manufactured from peripheral blood mononuclear cells given by intratumoral injection
Intervention Type
Radiation
Intervention Name(s)
External-beam radiotherapy (XRT)
Intervention Description
Radiotherapy given by external beam
Primary Outcome Measure Information:
Title
Incidence of treatment emergent adverse events (TEAEs) and adverse events (AEs)
Description
Includes evaluation of frequency and severity of AEs, serious adverse events (SAEs), TEAEs, and adverse events of special interest (AESIs), including injection site reactions and abnormalities in clinical laboratory assessments, vital signs, or physical examination findings. Graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.
Time Frame
Day -42 through Day 364
Secondary Outcome Measure Information:
Title
Recommended phase 2 dose of autologous SIRPant-M +/- 2.5 Gy ×3 focal XRT
Description
Based on review of safety, pharmacodynamic, and efficacy data.
Time Frame
Day 1 through Day 364
Title
Objective response rate (ORR)
Description
Based on number of participants with complete response (CR) and partial response (PR). Determined by positron emission tomography/computed tomography (PET/CT) and evaluated per the Lugano classification.
Time Frame
Day 1 through Day 364

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Adult, defined as age ≥ 18 (at screening), who are willing and able to provide informed consent Must have relapsed/refractory lymphoma, received at least 2 lines of systemic therapy, be ineligible or inappropriate for other treatment regimens known to have curative potential, and must have recovered from the acute toxic effects of all prior oncologic therapy of curative intent (except alopecia) Histologically or cytologically confirmed diagnosis of NHL, any one of the below: Eligible for SIRPant-M monotherapy or SIRPant-M plus focal XRT combination therapy: Diffuse large B-cell lymphoma and cutaneous T-cell lymphoma (CTCL), including mycosis fungoides (MF), Sezary Syndrome, anaplastic large cell lymphoma (ALCL), lymphomatoid papulosis; adult T-cell leukemia/lymphoma (ATLL); peripheral T cell lymphoma; and angioimmunoblastic T cell lymphoma Eligible for SIRPant-M monotherapy only: Cutaneous B-cell lymphoma, including primary cutaneous follicle center lymphoma and primary cutaneous marginal zone B-cell, leg type; follicular center lymphoma; chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL); mantle cell lymphoma (MCL); nodal marginal zone B-cell lymphoma Must have at least one accessible lymph node or cutaneous or subcutaneous lesion of 1.5 to 5 cm in one dimension as measured by computed tomography (CT) or positron emission tomography/computed tomography (PET/CT) or ultrasound for ITI by an interventional radiologist or other appropriately qualified and trained personnel, which presents a low risk for complications as determined by the Interventional Radiologist and the Principal Investigator. The target lesion must not have been previously irradiated. Note that lesions in the vicinity of large vessels, and tumor-encased large vessels are not considered low-risk. Additional caution should be taken in patients with neck lesions and lesions connected to ulcerated skin or mucosal surface. The target lesion must not be >5 cm in any dimension. Must have a life expectancy > 3 months; must also be confirmed within 7 days prior to Day 1 of SIRPant-M ITI treatment Must have an Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2; must also be confirmed within 7 days prior to Day 1 of SIRPant-M ITI treatment Must have hematologic values as follows: hemoglobin (Hgb) > 8 g/dL, ANC > 500 /mm3, monocyte counts ≥ 200/μL, and platelets > 50,000/µL; must also be confirmed within 7 days prior to Day 1 of SIRPant-M ITI treatment Must have adequate renal and hepatic function as follows: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <3× the upper limit of normal (ULN) (unless attributed to leukemic involvement or required concomitant medication) Calculated creatinine clearance ≥60 milliliter per minute (mL/min) calculated with Cockcroft-Gault formula Bilirubin ≤1.5×ULN, unless secondary to Gilbert's Syndrome. Must also be confirmed within 7 days prior to Day 1 of SIRPant-M ITI treatment. Cardiac function: Must be American Heart Association (AHA) class 1 without significant limitation of physical activity; must also be confirmed within 7 days prior to Day 1 of SIRPant-M ITI treatment. Must not be pregnant or planning to become pregnant. A negative urine or serum pregnancy test result is required for persons of reproductive potential within 72 hours prior to start of study treatment administration. All persons of reproductive potential must agree to use an effective contraceptive method during study participation and for a minimum of 90 days after study treatment. Biologically female: is premenarcheal, surgically sterile (post hysterectomy, bilateral salpingectomy, or bilateral oophorectomy), postmenopausal (>12 months of amenorrhea without alternative medical causes), or, if of reproductive potential, is using a highly effective method of contraception (combined estrogen/progestogen or progestogen-only hormonal contraceptives associated with inhibition of ovulation, intrauterine device [IUD], intrauterine hormone-releasing system [IUS], bilateral tubal occlusion/ligation, vasectomized partner[s], double barrier method [male condom with either cap, diaphragm, or sponge with spermicide], or true abstinence of heterosexual intercourse when this is in line with the preferred and usual lifestyle of the person [periodic abstinence, eg, calendar, ovulation, symptom-thermal, post-ovulation methods, and withdrawal are not acceptable methods of contraception]), and agrees to continued use of this method until 90 days after end of study treatment Biologically male: is vasectomized and has received medical assessment of surgical success, has undergone bilateral orchidectomy, or agrees to use an approved method of contraception (true abstinence of heterosexual intercourse when this is in line with the preferred and usual lifestyle of the person, double barrier method [male condom with either cap, diaphragm, or sponge with spermicide], partner's use of a highly effective method of contraception sterile, partner is postmenopausal, or partner is surgically sterile) and agrees to use this method until 90 days after study treatment In the opinion of the Investigator, must be willing and able to comply with the protocol for the duration of the study including undergoing treatment, the required tumor tissue biopsy procedures, scheduled visits and examinations, and including follow up Exclusion Criteria: Must not have received prior ITI therapy Must not have received ASCT or treatment with cellular therapy including CAR-T within the prior 1 month; must not have received allogeneic stem cell transplantation within prior 6 months and must have no active graft-versus-host disease (GVHD) or be under active immunosuppression for GVHD. Must not have received prior systemic anti-cancer therapy within the past 14 days before start of study cell therapy Must not have received IL-2 therapy within the last 6 months Must not have acquired immune defects such as human immunodeficiency virus (HIV) Must not have uncontrolled hypertension (systolic >180 mmHg, diastolic >100 mmHg) Must not have diagnosis of unclassifiable B cell lymphoma Must not have bleeding diathesis or abnormal values for prothrombin time (PT) or activated partial thromboplastin time (aPTT), international normalized ratio (INR) > 1.5× ULN Must not be receiving anti-platelet drugs that may present a risk for intratumor injections Must not have pulmonary disease which, in the opinion of the Investigator, might impair the patient's respiratory tolerance to moderate pulmonary fluid overload (eg, interstitial lung disease, severe chronic obstructive pulmonary disease) Must not have known alcohol or drug abuse Must not have received an investigational agent within the past 30 days before start of study cell therapy Must not require a chronic therapy with prednisone at a dose of or exceeding 10 mg/day or equivalent or any other form of immunosuppressive therapy Must not have active central nervous system tumors or metastases Must not be ineligible to receive 2.5 Gy ×3 focal external-beam radiation therapy as determined by the Radiation Oncologist and Principal Investigator (Cohort 1/Group 2, Cohort 2/Group 4, and Cohort -1/Group 4 only) Must not have uncontrolled active viral hepatitis-B, -C, and/or -D infection Must not have received a live vaccine within 4 weeks of the baseline/screening visit Must not have active, uncontrolled autoimmune disease and/or history of autoimmune diseases at high risk for relapse Must not have another malignancy or uncontrolled intercurrent illness, condition, serious medical or psychiatric illness, or circumstance that, in the opinion of the Investigator, could interfere with adherence to the study's procedures or requirements, or otherwise compromise the study's objectives No active systemic infection; must also be confirmed on Day 1 prior to initiation of ITI
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jelle Kijlstra, MD, MBA
Phone
610-321-3111
Email
jkijlstra@sirpantimmunotx.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jelle Kijlstra, MD, MBA
Organizational Affiliation
SIRPant Immunotherapeutics
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tatyana Feldman, MD
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Paolo Strati, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Study of SIRPant-M in Participants With Relapsed or Refractory Non-Hodgkin's Lymphoma

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