BEAM-201 for T-cell Leukemia/Lymphoma

Recruiting at 10 trial locations

Overseen By Medical Information

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Beam Therapeutics Inc.

Must not be taking: CD7 therapy

Disqualifiers: CNS involvement, Neurological toxicity, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Phase 1/2

5 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase 1/2, multicenter, open-label study to evaluate the safety and efficacy of BEAM-201 in patients with relapsed/refractory T-ALL or T-LL. This study consists of Phase 1 dose-exploration cohorts, Phase 1 dose-expansion cohort(s), a Phase 1 pediatric cohort (will enroll patients ages 1 to \< 12 years), and a Phase 2 cohort.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications. However, you cannot have received systemic antileukemic therapy intended to induce or maintain remission within 14 days before completing screening.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have received systemic antileukemic therapy intended to induce or maintain remission within 14 days before completing screening.

What data supports the idea that BEAM-201 for T-cell Leukemia/Lymphoma (also known as: BEAM-201, BEAM-201) is an effective treatment?

The available research does not provide specific data on BEAM-201 for T-cell Leukemia/Lymphoma. Instead, it discusses total skin electron beam therapy (TSEB) for a related condition, mycosis fungoides, which is a type of T-cell lymphoma. In one case, a patient with advanced-stage mycosis fungoides showed a nearly complete response to low-dose TSEB, remaining in remission for over four years. However, this information does not directly support the effectiveness of BEAM-201 for T-cell Leukemia/Lymphoma. ^{1 2 3 4 5}

What safety data is available for BEAM-201 treatment in T-cell Leukemia/Lymphoma?

The provided research does not contain specific safety data for BEAM-201 treatment in T-cell Leukemia/Lymphoma. The articles focus on CAR-T cell therapies for B-cell malignancies, such as diffuse large B-cell lymphoma and acute lymphoblastic leukemia, and discuss adverse events like cytokine release syndrome and neurological toxicity. However, these findings may not directly apply to BEAM-201 or T-cell Leukemia/Lymphoma. ^{6 7 8 9 10}

What safety data exists for BEAM-201 or similar treatments in humans?

CAR-T cell therapies, similar to BEAM-201, have been studied for other conditions and are known to cause side effects like cytokine release syndrome (a severe immune reaction) and neurological issues. These side effects are generally manageable with proper medical care. ^{6 7 8 9 10}

Is the treatment BEAM-201 a promising treatment for T-cell Leukemia/Lymphoma?

The information provided does not directly mention BEAM-201, so we cannot determine if it is a promising treatment for T-cell Leukemia/Lymphoma based on the given articles. ^{2 4 5 11 12}

Eligibility Criteria

This trial is for people aged 1 to 50 with T-Cell Acute Lymphoblastic Leukemia or T-Cell Lymphoblastic Lymphoma that has come back or didn't respond to treatment. They should have a certain amount of cancer cells in their bone marrow or evidence of the disease after a second remission, and be eligible for a type of stem cell transplant.

Inclusion Criteria

I am approved for a stem cell transplant and have a donor.

My T-ALL/T-LL cancer is in its second or later relapse, has come back after a transplant, or hasn't responded to chemotherapy.

I am between 1 and 17 years old.

Exclusion Criteria

I have previously received CD7 targeted therapy.

I have received treatment for leukemia within the last 14 days.

I have brain-related symptoms or permanent nerve damage from past leukemia treatments.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Participants receive a lymphodepletion regimen including fludarabine, cyclophosphamide, and optionally alemtuzumab

1-2 weeks

Treatment

Participants receive BEAM-201 CAR-T cells

Phase 1/2

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• BEAM-201

Trial Overview The study tests BEAM-201's safety and effectiveness on patients with relapsed/refractory T-ALL/T-LL. It includes initial dose-finding, expansion cohorts, a pediatric group (ages 1 to <12), and Phase 2 cohort to determine how well it works at selected doses.

Participant Groups

Group I: Fludarabine, cyclophosphamide without alemtuzumab Experimental Treatment 1 Intervention

Lymphodepletion regimen without Alz but consisting of the same dose of Flu/Cy as in the other arm

Group II: Fludarabine, cyclophosphamide and alemtuzumab Experimental Treatment 1 Intervention

Lymphodepletion regimen including fludarabine, cyclophosphamide and alemtuzumab

Who Is Running the Clinical Trial?

Beam Therapeutics Inc.

Lead Sponsor

Trials

5

Recruited

1,200+

Findings from Research

A case study of a 50-year-old male with rapidly progressive stage IVB mycosis fungoides showed a remarkable 95% response to low-dose total skin electron beam (TSEB) therapy (24 Gy over 8 weeks) with no apparent side effects, highlighting its potential efficacy even in advanced disease.

The patient has remained in remission for over 4 years after treatment, suggesting that low-dose TSEB can be a viable option for managing advanced-stage mycosis fungoides, which is typically considered palliative.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapidly progressive stage IVB mycosis fungoides treated with low-dose total skin electron beam therapy. Chowdhary, M., Kabbani, AA., Rimtepathip, P., et al.[2022]

In patients with advanced-stage cutaneous T-cell lymphoma (CTCL) who achieved a complete response after total skin electron beam therapy (TSEBT), the adjuvant therapy of extracorporeal photochemotherapy (ECP) showed a potential survival benefit, with 100% overall survival at 3 years for T3 and T4 patients, compared to approximately 50% for those who received no adjuvant therapy.

Conversely, the combination of doxorubicin and cyclophosphamide did not significantly improve overall survival for patients who achieved a complete response to TSEBT, and neither adjuvant therapy affected relapse-free survival across all T-stages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic chemotherapy and extracorporeal photochemotherapy for T3 and T4 cutaneous T-cell lymphoma patients who have achieved a complete response to total skin electron beam therapy. Wilson, LD., Licata, AL., Braverman, IM., et al.[2019]

Total skin electron beam radiation treatment for mycosis fungoides resulted in an 82% overall complete response rate, with better outcomes for patients with lower T stages (T1) compared to higher stages (T2-4).

Patients with T1N0 mycosis fungoides who received 35 Gy had a remarkable 10-year mycosis fungoides-specific survival rate of 100%, indicating the effectiveness of this treatment for early-stage disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognosis with newly diagnosed mycosis fungoides after total skin electron radiation of 30 or 35 GY. Jones, GW., Tadros, A., Hodson, DI., et al.[2019]

In a study of 14 patients with primary cutaneous T-cell lymphoma (PCTCL) treated with total skin electron beam therapy (TSEBT), the overall response rate was 85% after 6-8 weeks, indicating that TSEBT is an effective treatment option for this condition.

The study found that low-dose TSEBT (12 Gy) is preferred due to its effectiveness and the possibility of retreatment, with a median progression-free survival of 6 months for the cohort, highlighting its role in managing advanced stages of PCTCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Total skin electron beam therapy for primary cutaneous T-cell lymphomas: clinical characteristics and outcomes in a Mexican reference center. Flores-Balcázar, C., Urías-Arce, DM., Charli-Joseph, Y., et al.[2022]

Total skin electron beam therapy (TSEB) demonstrated a high efficacy in treating early-stage mycosis fungoides, with a complete clinical response in 97% of patients three months after treatment, based on a retrospective study of 68 patients.

Despite some acute toxicity, such as localized ulcerations in 13.2% of patients, TSEB showed favorable long-term outcomes with 5-year overall survival rates of 86% and disease-free survival rates of 41%, suggesting it should be considered a first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Total skin electron beam therapy for early-stage mycosis fungoides: immediate results and long-term follow-up in 68 patients]. Goujon, E., Truc, G., Pétrella, T., et al.[2009]

Chimeric antigen receptor (CAR)-T cell therapy, specifically targeting CD19, has shown promising results in treating non-Hodgkin lymphomas (NHLs) resistant to standard therapies, leading to FDA and EMA approvals for tisagenlecleucel and axicabtagene ciloleucel.

While CAR-T cell therapy can cause significant adverse events like cytokine release syndrome and neurological toxicity, these effects are manageable with proper medical support, highlighting the importance of trained teams in administering this novel treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope. Hopfinger, G., Jäger, U., Worel, N.[2020]

The FDA has approved three innovative therapies for relapsed/refractory B-cell acute lymphoblastic leukemia, including inotuzumab ozogamicin and blinatumomab, which have significantly changed treatment options for this disease.

Understanding the unique toxicities and adverse effects of these therapies is crucial for safe administration, and the article provides recommendations for preventing and managing these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of adverse effects of new monoclonal antibody treatments in acute lymphoblastic leukemia. Conde-Royo, D., Juárez-Salcedo, LM., Dalia, S.[2020]

CAR T cell therapy, specifically tisagenlecleucel, has transformed the treatment landscape for pediatric patients with relapsed or refractory B-cell acute lymphoblastic leukemia, leading to significant advancements in immunooncology.

Ongoing research is focused on enhancing the efficacy and safety of CAR T cells, as well as addressing challenges related to patient access to this innovative therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential of CAR T therapy for relapsed or refractory pediatric and young adult B-cell ALL. Forsberg, MH., Das, A., Saha, K., et al.[2020]

Brexucabtagene autoleucel is the first FDA-approved CAR T-cell therapy targeting CD19 for adults with relapsed and refractory B-cell acute lymphoblastic leukemia, marking a significant advancement in treatment options.

The approval was based on the outcomes of the Zuma-3 trial, which demonstrated the efficacy of this therapy in improving patient outcomes in a challenging-to-treat population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Approval of brexucabtagene autoleucel for adults with relapsed and refractory acute lymphocytic leukemia. Frey, NV.[2022]

In the phase 3 TOWER study, blinatumomab showed a significant overall survival benefit compared to standard-of-care chemotherapy in adults with relapsed or refractory Philadelphia chromosome-negative B-precursor acute lymphoblastic leukemia, involving 267 patients who received a median of 2 cycles of treatment.

After adjusting for treatment duration, blinatumomab had lower exposure-adjusted event rates for serious adverse events compared to standard chemotherapy, particularly for infections and cytopenias, indicating it is a well-tolerated treatment option despite a higher rate of cytokine-release syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exposure-adjusted adverse events comparing blinatumomab with chemotherapy in advanced acute lymphoblastic leukemia. Stein, AS., Larson, RA., Schuh, AC., et al.[2020]

Patients with acute adult T-cell leukemia/lymphoma (ATL) show significant benefits from first-line combined antiviral therapy using zidovudine and interferon alpha, while those with lymphoma-type ATL may respond better to intensive chemotherapy.

Allogeneic stem-cell transplantation offers promising outcomes, with up to 40% of patients achieving long-term survival after remission, highlighting the need for further research into effective treatment strategies for different ATL subsets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Newer developments in adult T-cell leukemia/lymphoma therapeutics. Dasanu, CA.[2013]

In a phase 2 trial involving 349 patients with newly diagnosed T-cell acute lymphoblastic leukaemia, the ALL-T11 protocol achieved a high 3-year event-free survival rate of 86.4% and an overall survival rate of 91.3%, indicating effective treatment outcomes with reduced reliance on cranial radiotherapy and stem cell transplantation.

The study demonstrated that the addition of nelarabine and intensified L-asparaginase therapy led to a high complete remission rate of 89%, while the treatment was associated with manageable side effects, including a low incidence of severe neuropathy and febrile neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nelarabine, intensive L-asparaginase, and protracted intrathecal therapy for newly diagnosed T-cell acute lymphoblastic leukaemia in children and young adults (ALL-T11): a nationwide, multicenter, phase 2 trial including randomisation in the very high-risk group. Sato, A., Hatta, Y., Imai, C., et al.[2023]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Rapidly progressive stage IVB mycosis fungoides treated with low-dose total skin electron beam therapy. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Systemic chemotherapy and extracorporeal photochemotherapy for T3 and T4 cutaneous T-cell lymphoma patients who have achieved a complete response to total skin electron beam therapy. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Prognosis with newly diagnosed mycosis fungoides after total skin electron radiation of 30 or 35 GY. [2019]

4. Poland pubmed.ncbi.nlm.nih.gov

Total skin electron beam therapy for primary cutaneous T-cell lymphomas: clinical characteristics and outcomes in a Mexican reference center. [2022]

5. France pubmed.ncbi.nlm.nih.gov

[Total skin electron beam therapy for early-stage mycosis fungoides: immediate results and long-term follow-up in 68 patients]. [2009]

6. United States pubmed.ncbi.nlm.nih.gov

CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Management of adverse effects of new monoclonal antibody treatments in acute lymphoblastic leukemia. [2020]

8. New Zealand pubmed.ncbi.nlm.nih.gov

The potential of CAR T therapy for relapsed or refractory pediatric and young adult B-cell ALL. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Approval of brexucabtagene autoleucel for adults with relapsed and refractory acute lymphocytic leukemia. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Exposure-adjusted adverse events comparing blinatumomab with chemotherapy in advanced acute lymphoblastic leukemia. [2020]

11. England pubmed.ncbi.nlm.nih.gov

Newer developments in adult T-cell leukemia/lymphoma therapeutics. [2013]

12. England pubmed.ncbi.nlm.nih.gov

Nelarabine, intensive L-asparaginase, and protracted intrathecal therapy for newly diagnosed T-cell acute lymphoblastic leukaemia in children and young adults (ALL-T11): a nationwide, multicenter, phase 2 trial including randomisation in the very high-risk group. [2023]