SIRPant-M + Radiotherapy for Non-Hodgkin's Lymphoma

Recruiting at 2 trial locations

Overseen By Jelle Kijlstra, MD, MBA

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: SIRPant Immunotherapeutics, Inc.

Must not be taking: Anti-platelet drugs, Immunosuppressants

Disqualifiers: HIV, Uncontrolled hypertension, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 3 weeks per cycle

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called SIRPant-M, a type of cell therapy, to determine its safety and tolerability in people with non-Hodgkin's lymphoma that hasn't responded to other treatments. The study examines SIRPant-M alone and in combination with radiotherapy (external-beam radiotherapy, XRT) to assess its effectiveness. Participants should have a form of non-Hodgkin's lymphoma that has returned or hasn't improved with at least two previous treatments and isn't suitable for other therapies. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must not be on certain treatments like prednisone at high doses or other immunosuppressive therapies, and you should not have received certain cancer therapies or investigational agents recently.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that SIRPant-M has received special status from the FDA for treating T-cell lymphoma, indicating promise and safety in early tests. However, current studies remain in the early stages, requiring more information to fully understand its safety in humans. Initial findings suggest that researchers are testing the treatment to determine if it is well-tolerated, both alone and with low-dose radiotherapy. While specific safety details are not yet available, this early phase of research involves close monitoring for any possible side effects. Participants should consult their doctors to consider the potential risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about SIRPant-M for treating Non-Hodgkin's Lymphoma because it uses a novel approach by harnessing modified immune cells to target cancer. Unlike traditional therapies like chemotherapy or radiation alone, SIRPant-M combines modified immune cells with low-dose radiotherapy to potentially enhance its cancer-fighting effects. This dual approach not only aims to improve effectiveness but may also reduce the side effects typically associated with higher doses of radiation. The potential for more targeted action and fewer side effects is what makes SIRPant-M a promising treatment option in the fight against lymphoma.

What evidence suggests that this trial's treatments could be effective for non-Hodgkin's lymphoma?

Research has shown that SIRPant-M, a type of personalized cell therapy, holds potential for treating non-Hodgkin's lymphoma (NHL). In early tests, SIRPant-M proved effective against various solid tumors. The FDA has recognized this therapy as promising for T-cell lymphoma, suggesting it could aid in treating blood cancers like NHL. In this trial, participants will receive different dosages of SIRPant-M, either as monotherapy or in combination with radiotherapy. When combined with radiotherapy, SIRPant-M might enhance treatment outcomes, as radiotherapy alone has been successful in treating NHL. These findings suggest that SIRPant-M, particularly when paired with radiotherapy, could benefit individuals whose NHL has returned or is unresponsive to other treatments. ^{1 2 3 4 5}

Who Is on the Research Team?

Jelle Kijlstra, MD, MBA

Principal Investigator

BobcatBio, p/k/a SIRPant Immunotherapeutics

Are You a Good Fit for This Trial?

Adults over 18 with relapsed or refractory non-Hodgkin's lymphoma who've tried at least two systemic therapies can join this trial. They need to have a certain level of organ function, an accessible tumor for treatment, and not be pregnant. Participants must agree to use effective contraception and cannot have autoimmune diseases, recent other cancer treatments, uncontrolled illnesses, or active infections.

Inclusion Criteria

I have a tumor or lymph node between 1.5 and 5 cm that can be easily accessed.

Must not be pregnant or planning to become pregnant

My heart is functioning within normal limits.

Exclusion Criteria

I have not had a stem cell transplant from a donor in the last 6 months.

Must not have bleeding diathesis or abnormal values for PT or aPTT

I do not have an active, uncontrolled hepatitis infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

6 weeks

Treatment

Participants receive SIRPant-M alone or in combination with focal external-beam radiotherapy. Treatment involves intra-tumoral injections and may include radiation.

3 weeks per cycle

3 visits (in-person) per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

52 weeks

Extension

Participants with partial response or sustained clinical benefit may receive a second cycle of treatment

3 weeks per cycle

What Are the Treatments Tested in This Trial?

Interventions

• External-beam radiotherapy (XRT)
• SIRPant-M

Trial Overview The study is testing SIRPant-M cell therapy alone or combined with targeted radiotherapy in people with tough-to-treat non-Hodgkin's lymphoma. It aims to find out if these treatments are safe and how well patients tolerate them.

How Is the Trial Designed?

Group I: SIRPant-M (90×10^6 cells) with focal XRT Experimental Treatment 2 Interventions

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

Group II: SIRPant-M (90×10^6 cells) Experimental Treatment 1 Intervention

SIRPant-M Monotherapy (Single Agent)

Group III: SIRPant-M (600×10^6 cells) with focal XRT, alternate Day 1, 3, 5 IT-dosing Experimental Treatment 2 Interventions

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

Group IV: SIRPant-M (600×10^6 cells) coupled with focal XRT, weekly (W1, 2, 3) IT-dosing Experimental Treatment 2 Interventions

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

Group V: SIRPant-M (300×10^6 cells) with focal XRT Experimental Treatment 2 Interventions

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

Group VI: SIRPant-M (300×10^6 cells) Experimental Treatment 1 Intervention

SIRPant-M Monotherapy (Single Agent)

SIRPant-M is already approved in United States for the following indications:

Approved in United States as SIRPant-M for:

• Orphan drug designation for T-cell lymphoma

Who Is Running the Clinical Trial?

SIRPant Immunotherapeutics, Inc.

Lead Sponsor

Trials

1

Recruited

20+

Published Research Related to This Trial

Radiotherapy is highly effective for non-Hodgkin's lymphomas (NHL), potentially curing about 50% of patients with both low-grade and high-grade malignant NHL at stage I, based on a review of 158 studies involving 14,137 patients.

While radiotherapy is less effective for advanced stages (III and IV), it is particularly beneficial for localized extranodal diseases, such as MALT lymphoma, and can also serve a valuable role in palliative care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-Hodgkin's lymphomas (NHL). Gustafsson, A.[2019]

The standard treatment for high-grade non-Hodgkin's lymphoma is the CHOP chemotherapy regimen, which achieves complete remission in about two-thirds of patients, although many remissions are not long-lasting.

Current research is exploring the effectiveness of high-dose chemotherapy with hematopoietic stem cell support, particularly in young patients with high-risk factors, to improve long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment strategy of high malignancy non-Hodgkin lymphomas]. Pfreundschuh, M., Trümper, L.[2015]

In a study of 32 patients with gastric MALT lymphoma, radiation therapy (RT) at a reduced dose of 24 Gy resulted in a complete response in all patients, demonstrating its efficacy compared to the standard dose of ≥30 Gy.

The outcomes for freedom from local treatment failure (FFLTF), freedom from treatment failure (FFTF), and overall survival (OS) were excellent for both the 24 Gy and ≥30 Gy groups, indicating that lower doses may be just as effective as higher doses in achieving disease control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes After Reduced-Dose Intensity Modulated Radiation Therapy for Gastric Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma. Pinnix, CC., Gunther, JR., Milgrom, SA., et al.[2020]

In patients with Stage I follicular non-Hodgkin's lymphoma, regional radiotherapy alone yields excellent long-term relapse-free survival, while initial chemotherapy with CVP improves relapse-free survival but not total survival.

For Stage II diffuse histology, more aggressive chemotherapy is necessary as CVP does not improve outcomes, and combining localized radiotherapy with aggressive chemotherapy shows promising results for better survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic factors in non-Hodgkin's lymphoma. Tubiana, M., Carde, P., Burgers, JM., et al.[2019]

Radiotherapy is an effective treatment option for various types of non-Hodgkin lymphoma, particularly for low-grade forms and specific situations in high-grade cases, as indicated by recent studies.

A randomized trial found no significant difference in outcomes between low and high doses of radiotherapy, suggesting that lower doses may be sufficient for effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Role of radiotherapy in the management of non-Hodgkin lymphomas]. Gastaud, L., Rossignol, B., Peyrade, F., et al.[2018]

Radioimmunotherapy (RIT), specifically (90)Y-ibritumomab tiuxetan, has been approved for treating relapsed or refractory B-cell lymphoma, demonstrating efficacy that is largely independent of the anti-CD20 antibody's intrinsic activity.

While RIT offers increased effectiveness compared to standard antibody treatments, it does come with a risk of myelotoxicity, which is dose-limiting but reversible, highlighting the need for careful management in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radioimmunotherapy for non-Hodgkin's lymphoma. Emmanouilides, C.[2019]

The Phase I study of 90Y-2IT-BAD-Lym-1 in patients with chemotherapy-resistant B-cell non-Hodgkin's lymphoma established a maximum tolerated dose (MTD) of 0.370 GBq/m2, with myelotoxicity being the primary dose-limiting factor, particularly thrombocytopenia.

Out of 8 patients treated, 5 showed a partial response or stabilization of their NHL, indicating that 90Y-2IT-BAD-Lym-1 may be an effective treatment option, warranting further clinical trials despite the need for bone marrow support during higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of 90Y-2IT-BAD-Lym-1 in patients with non-Hodgkin's lymphoma. O'Donnell, RT., Shen, S., Denardo, SJ., et al.[2016]

Radioimmunotherapy (RIT) using agents like 90Y ibritumomab tiuxetan and 131I tositumomab has shown significant clinical efficacy in treating non-Hodgkin's lymphoma (NHL), especially in patients who did not respond well to previous treatments.

While RIT is generally safe, it can cause reversible side effects such as neutropenia, thrombocytopenia, and anemia, highlighting the importance of a collaborative approach among healthcare professionals in managing treatment and monitoring patient responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radioimmunotherapy for non-Hodgkin's lymphoma: a review for radiation oncologists. Macklis, RM., Pohlman, B.[2019]

Radioimmunotherapy (RIT) has shown effectiveness in treating non-Hodgkin's lymphoma but has had limited success with solid tumors when used alone, highlighting the need for improved therapeutic strategies.

Combining RIT with other treatments (CMRIT) and using nanoparticles for targeted delivery may enhance its effectiveness against solid tumors, with careful attention to the timing and sequence of therapies to maximize benefits and minimize side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted radionuclide therapy for solid tumors: an overview. DeNardo, SJ., Denardo, GL.[2007]

The study demonstrated a reliable dosimetry method for radioimmunotherapy (RIT) in treating relapsed non-Hodgkin's lymphoma, which is crucial for minimizing myelosuppression, a common side effect in heavily pretreated patients.

A significant correlation was found between the whole-body effective half-life of the antibody and the effective marrow half-life, indicating that personalized dosimetry can enhance the safety and efficacy of RIT by tailoring radiation doses to individual patient characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Validation of prospective whole-body bone marrow dosimetry by SPECT/CT multimodality imaging in (131)I-anti-CD20 rituximab radioimmunotherapy of non-Hodgkin's lymphoma. Boucek, JA., Turner, JH.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05967416?term=NCT05967416&rank=1

Study of SIRPant-M in Participants With Relapsed or ... The goal of this study is to test SIRPant-M (RB-1355) , an autologous cell therapy, alone or in combination with focal external-beam radiotherapy in ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05967416

NCT05967416 | Study of SIRPant-M in Participants With ... The goal of this study is to test SIRPant-M (RB-1355) , an autologous cell therapy, alone or in combination with focal external-beam radiotherapy in ...

3. onclive.com onclive.com/view/fda-grants-orphan-drug-designation-to-sirpant-m-in-t-cell-lymphoma

FDA Grants Orphan Drug Designation to SIRPant-M in T- ... The FDA has granted an orphan drug designation to SIRPant-M™ as a potential therapeutic option for patients with T-cell lymphoma.

4. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2023-0610.html

Phase 1, open-label study of Autologous SIRPa-low ... The goal of this study is to test SIRPant-M (RB-1355) , an autologous cell therapy, alone or in combination with focal external-beam radiotherapy in ...

5. targetedonc.com targetedonc.com/view/sirpant-m-receives-fda-orphan-drug-designation-for-t-cell-lymphoma

SIRPant-M Receives FDA Orphan Drug Designation for T- ... A phase 1 clinical trial (NCT05967416) of SIRPant-M is currently underway in patients with relapsed/refractory non-Hodgkin lymphoma (NHL). An ...