Trial Title:
Study of SIRPant-M in Participants With Relapsed or Refractory Non-Hodgkin's Lymphoma
NCT ID:
NCT05967416
Condition:
Refractory Non-Hodgkin Lymphoma
Relapsed Non-Hodgkin Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, Non-Hodgkin
Conditions: Keywords:
Non-Hodgkin Lymphoma
Relapsed/Refractory Non-Hodgkin Lymphoma
Autologous cell therapy
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Intervention 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.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
SIRPant-M
Description:
Autologous activated macrophage cell therapy manufactured from peripheral blood
mononuclear cells given by intratumoral injection
Arm group label:
SIRPant-M (300×10^6 cells)
Arm group label:
SIRPant-M (300×10^6 cells) coupled with focal XRT
Arm group label:
SIRPant-M (90×10^6 cells)
Arm group label:
SIRPant-M (90×10^6 cells) coupled with focal XRT
Intervention type:
Radiation
Intervention name:
External-beam radiotherapy (XRT)
Description:
Radiotherapy given by external beam
Arm group label:
SIRPant-M (300×10^6 cells) coupled with focal XRT
Arm group label:
SIRPant-M (90×10^6 cells) coupled with focal XRT
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Adult, defined as age ≥ 18 (at screening), who are willing and able to provide
informed consent
2. 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)
3. Histologically or cytologically confirmed diagnosis of NHL, any one of the below:
1. 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
2. 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
4. 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.
5. Must have a life expectancy > 3 months; must also be confirmed within 7 days prior
to Day 1 of SIRPant-M ITI treatment
6. 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
7. 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
8. Must have adequate renal and hepatic function as follows:
1. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <3× the
upper limit of normal (ULN) (unless attributed to leukemic involvement or
required concomitant medication)
2. Calculated creatinine clearance ≥60 milliliter per minute (mL/min) calculated
with Cockcroft-Gault formula
3. 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.
9. 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.
10. 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.
11. 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.
1. 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
2. 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
12. 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:
1. Must not have received prior ITI therapy
2. 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.
3. Must not have received prior systemic anti-cancer therapy within the past 14 days
before start of study cell therapy
4. Must not have received IL-2 therapy within the last 6 months
5. Must not have acquired immune defects such as human immunodeficiency virus (HIV)
6. Must not have uncontrolled hypertension (systolic >180 mmHg, diastolic >100 mmHg)
7. Must not have diagnosis of unclassifiable B cell lymphoma
8. 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
9. Must not be receiving anti-platelet drugs that may present a risk for intratumor
injections
10. 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)
11. Must not have known alcohol or drug abuse
12. Must not have received an investigational agent within the past 30 days before start
of study cell therapy
13. 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
14. Must not have active central nervous system tumors or metastases
15. 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)
16. Must not have uncontrolled active viral hepatitis-B, -C, and/or -D infection
17. Must not have received a live vaccine within 4 weeks of the baseline/screening visit
18. Must not have active, uncontrolled autoimmune disease and/or history of autoimmune
diseases at high risk for relapse
19. 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
20. No active systemic infection; must also be confirmed on Day 1 prior to initiation of
ITI
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
City of Hope
Address:
City:
Duarte
Zip:
91010
Country:
United States
Status:
Recruiting
Contact:
Last name:
Kimberly Cornejo-Peril
Phone:
626-218-7361
Email:
kcornejoperil@coh.org
Investigator:
Last name:
Christiane Querfeld, MD, PhD
Email:
Principal Investigator
Facility:
Name:
Hackensack University Medical Center
Address:
City:
Hackensack
Zip:
07601
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Tatyana Feldman, MD
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Paolo Strati, MD
Start date:
December 2023
Completion date:
March 2025
Lead sponsor:
Agency:
SIRPant Immunotherapeutics, Inc.
Agency class:
Industry
Source:
SIRPant Immunotherapeutics, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05967416
