SIRPant-M + Radiotherapy for Non-Hodgkin's Lymphoma
Recruiting in Palo Alto (17 mi)
+2 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: SIRPant Immunotherapeutics, Inc.
Must not be taking: Anti-platelet drugs, Immunosuppressants
Disqualifiers: HIV, Uncontrolled hypertension, Autoimmune, others
No Placebo Group
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?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 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.
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.
What data supports the effectiveness of the treatment SIRPant-M + Radiotherapy for Non-Hodgkin's Lymphoma?
Research shows that radioimmunotherapy (RIT), a treatment similar to SIRPant-M, has been effective for non-Hodgkin's lymphoma, especially in cases resistant to chemotherapy. Studies have demonstrated that RIT can target and destroy cancer cells, making it a promising approach for treating this type of lymphoma.
12345What makes the treatment SIRPant-M unique for non-Hodgkin's lymphoma?
SIRPant-M is unique because it combines with radiotherapy, which is already effective for non-Hodgkin's lymphoma, potentially enhancing its effects. This combination could offer a novel approach compared to standard chemotherapy regimens like CHOP, especially for patients who may not respond well to traditional treatments.
678910Eligibility Criteria
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.
My heart is functioning within normal limits.
Must not be pregnant or planning to become pregnant
+10 more
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.
+18 more
Trial Timeline
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
Participant Groups
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.
6Treatment groups
Experimental Treatment
Group I: SIRPant-M (90×10^6 cells) with focal XRTExperimental Treatment2 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 Treatment1 Intervention
SIRPant-M Monotherapy (Single Agent)
Group III: SIRPant-M (600×10^6 cells) with focal XRT, alternate Day 1, 3, 5 IT-dosingExperimental Treatment2 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-dosingExperimental Treatment2 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 XRTExperimental Treatment2 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 Treatment1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Hackensack University Medical CenterHackensack, NJ
MD Anderson Cancer CenterHouston, TX
City of HopeDuarte, CA
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Who Is Running the Clinical Trial?
SIRPant Immunotherapeutics, Inc.Lead Sponsor
References
A phase I study of 90Y-2IT-BAD-Lym-1 in patients with non-Hodgkin's lymphoma. [2016]Prior clinical trials proved that all histologic grades of chemotherapy-resistant B-cell non-Hodgkin's lymphoma (NHL) could respond to radio-immunotherapy (RIT) with 131I-Lym-1 and 67Cu-2IT-BAT-Lym-1. This Phase I study was conducted to determine the safety and maximum tolerated dose (MTD) of 90Y-2IT-BAD-Lym-1.
Radioimmunotherapy for non-Hodgkin's lymphoma: a review for radiation oncologists. [2019]The aim of this study was to review advances in radioimmunotherapy (RIT) for non-Hodgkin's lymphoma (NHL) and to discuss the role of the radiation oncologist in administering this important new form of biologically targeted radiotherapy.
Targeted radionuclide therapy for solid tumors: an overview. [2007]Although radioimmunotherapy (RIT) has been effective in non-Hodgkin's lymphoma (NHL) as a single agent, solid tumors have shown less clinically significant therapeutic response to RIT alone. The clinical impact of RIT or other forms of targeted radionuclide therapy for solid tumors depends on the development of a high therapeutic index (TI) for the tumor vs. normal tissue effect, and the implementation of RIT as part of synergistic combined modality therapy (CMRIT). Preclinical and clinical studies have provided a wealth of information, and new prototypes or paradigms have shed light on future possibilities in many instances. Evidence suggests that combination and sequencing of RIT in CMRIT appropriately can provide effective treatment for many solid tumors. Vascular targets provide RIT enhancement opportunities and nanoparticles may prove to be effective carriers for RIT combined with intracellular drug delivery or alternating magnetic frequency (AMF) induced thermal tumor necrosis. The sequence and timing of combined modality treatments will be of critical importance to achieve synergy for therapy while minimizing toxicity. Fortunately, the radionuclide used for RIT also provides a signal useful for nondestructive quantitation of the influence of sequence and timing of CMRIT on events in animals and patients. This can be readily accomplished clinically using quantitative high-resolution imaging (e.g., positron emission tomography [PET]).
Radioimmunotherapy for non-Hodgkin's lymphoma. [2019]Radioimmunotherapy (RIT) treatment for lymphoma is a novel targeted therapeutic approach. Several years of development of radioimmunotherapeutic compounds came to fruition in February of 2002 when the US Food and Drug Administration (FDA) approved yttrium 90 ((90)Y)-ibritumomab tiuxetan ((90)Y-IT) for the treatment of relapsed or refractory, low-grade, or transformed B-cell lymphoma. (90)Y-IT uses a monoclonal anti-CD20 antibody to deliver beta-emitting (90)Y to the malignant B cells. Clinical trials have demonstrated its efficacy, which is largely independent of the intrinsic activity of the anti-CD20 antibody. A similar anti-CD20 radiotherapeutic compound, iodine 131 ((131)I)-tositumomab ((131)I-T), is also under consideration for approval. The advantages of increased efficacy compared to the native antibody are gained at the expense of myelotoxicity, which is dose-limiting but reversible. Other radioimmunoconjugates (RIC), including products for Hodgkin's lymphoma, are in earlier stages of development. Studies exploring expanded applications of RIT are under way. RIT has been shown to be an effective and clinically relevant complementary therapeutic approach for patients with lymphoma.
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. [2018]Radioimmunotherapy (RIT) for relapsed non-Hodgkin's lymphoma is emerging as a promising treatment strategy. Myelosuppression is the dose-limiting toxicity and may be particularly problematic in patients heavily pretreated with chemotherapy. Reliable dosimetry is likely to minimise toxicity and improve treatment efficacy, and the aim of this study was to elucidate the complex problems of dosimetry of RIT by using an integrated SPECT/CT system.
Non-Hodgkin's lymphomas (NHL). [2019]This synthesis of the literature on radiotherapy for non-Hodgkin's lymphomas is based on 158 scientific articles, including 16 randomized studies, 18 prospective studies, and 90 retrospective studies. These studies involve 14,137 patients. Non-Hodgkin's lymphomas are highly radiosensitive, and local recurrence following radiotherapy is unusual. Radiotherapy probably cures approximately 50% of both low-grade and high-grade malignant NHL at stage I. Involved field is apparently sufficient, however, higher doses are required for high-grade malignant lymphomas. Chemotherapy is recommended for stage II. Consolidation radiotherapy after chemotherapy may increase the number of complete remissions. The value of adjuvant radiotherapy has not been confirmed. Radiotherapy plays a limited role at stages III and IV. Radiotherapy is clearly indicated for extranodal localized disease in the skin and in the orbit of the eye. It is important to identify groups and subgroups in whom radiotherapy alone is sufficient, ie, the risk for distant recurrence is small. MALT lymphoma belongs to this group. Radiotherapy is often valuable in palliative situations.
[Treatment strategy of high malignancy non-Hodgkin lymphomas]. [2015]While radiotherapy is not justified as a single-modality approach in high-grade non-Hodgkin's lymphoma, standard therapy consists of chemotherapy with the CHOP regimen, which induces complete remissions in ca. 2/3 of the patients, with or without additional radiotherapy. Since the majority of these remissions do not last, dose escalations up to myeloablative ranges using hematopoietic stem cell support are being evaluated especially in young patients with bad risk factors. The trials of the German Non-Hodgkin's Lymphoma Consensus Trial group determine the value of a consolidating high-dose chemotherapy in young patients with high-risk profile, while dose intensifications of the CHOP regimen by two-week regimens and/or the incorporation of etoposide are being evaluated in all other treatment groups.
Outcomes After Reduced-Dose Intensity Modulated Radiation Therapy for Gastric Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma. [2020]In patients with gastric extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma, the standard radiation therapy (RT) dose is ≥30 Gy. We report the outcome of patients treated with reduced dose 24 Gy compared with those treated with ≥30 Gy.
Prognostic factors in non-Hodgkin's lymphoma. [2019]The results obtained with the various types of treatment in non-Hodgkin's lymphoma are reviewed and the data from the recent EORTC trials are summarized. In patients with Stage I follicular histology, regional radiotherapy (RT) alone gives excellent results. The long-term relapse-free survival (RFS) is high and relapsing patients can be rescued by aggressive combination chemotherapy; initial chemotherapy with CVP improves RFS but not total survival (TS). In patients with Stage I diffuse histology, the long-term survival is less satisfactory. CVP chemotherapy does not improve either RFS or TS; therefore if adjuvant chemotherapy is justified, it should be more aggressive than CVP. In patients with Stage II follicular type, regional radiotherapy alone gives good results. The addition of abdominal bath irradiation to regional RT increases RFS but not TS. After relapse, patients can be rescued by combination chemotherapy. In patients with Stage II diffuse histology, extended RT followed by CVP gives poor results and RT should be combined with more aggressive combination CT; the preliminary results of an integrated alternating regimen being excellent. In patients with Stage III and IV follicular type, the 8 year TS of patients treated with combination CT regimen (CHVP) followed by localized irradiation is approximately 55%, however the indications for the various types of treatment are still unclear. In patients with diffuse Stage III and IV, the results obtained with a combination CT regimen (CHVP) are still unsatisfactory, but are better in patients treated by a more aggressive CT regimen (CHVP-Bleo-VCR). Therefore aggressive CT associated with localized irradiation appears to be the best treatment. Further research should aim to identify the optimal combination CT regimen. In patients with high grade lymphomas who have relapsed the use of bone marrow autografts will be investigated. The present data show that besides histological type and age, the main prognostic factor is total tumor body burden as assessed by clinical stage, number of involved lymph node areas, and bulk of the disease. The study of the biological characteristics of the disease may provide more powerful prognostic indicators.
[Role of radiotherapy in the management of non-Hodgkin lymphomas]. [2018]The purpose of this review was to summarize recent data about lastest retrospective and prospective studies dealing with radiotherapy of non-Hodgkin lymphoma, in order to precise the schedule and the role of this treatment. A systematic review was done by searching studies on the website http://www.pubmed.gov (Medline) using the following keywords: radiotherapy, radiation therapy, non-Hodgkin lymphoma. The management of non-Hodgkin lymphoma varies a lot according to the histological type and stage. The dose of radiotherapy has been studied in only one randomized trial, which concluded that there was no difference between the low dose and the high dose arms. Radiotherapy is a very good option in follicular, cutaneous, digestive or orbital non-Hodgkin lymphoma. A recent post hoc analysis of randomized trials on radiotherapy for high-grade non-Hodgkin lymphoma strongly suggested a benefit of additional radiotherapy after chemotherapy in some situations. Radiotherapy of low-grade non-Hodgkin lymphoma is a very good option, while its use on high-grade non-Hodgkin lymphoma is sometimes recommended but further randomized trials are ongoing to better understand its role.