MT-601 for Lymphoma

(APOLLO Trial)

Recruiting at 6 trial locations

Overseen By Patricia Allison

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Marker Therapeutics, Inc.

Must not be taking: Immunosuppressants, Corticosteroids, Chemotherapy, others

Disqualifiers: CNS pathology, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: Unknown

79 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is a Phase 1 multicenter study with a Dose Escalation and Dose Expansion evaluating safety and efficacy of MT-601 administration to patients with Relapsed or Refractory Lymphoma. The starting dose administered is 200 x 10\^6 cells (flat dosing).

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, certain treatments like chemotherapy, monoclonal antibodies, and systemic immunosuppressants must be stopped within specific timeframes before participating. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the treatment MT-601, Neldaleucel, for lymphoma?

Research on similar treatments, like the use of anti-PD-1 antibodies in lymphoma, shows promising results in improving patient outcomes by helping the immune system fight cancer cells more effectively. This suggests that treatments targeting the PD-1/PD-L1 pathway, like MT-601, could potentially be effective for lymphoma. ^{1 2 3 4 5}

What makes the drug MT-601 (Neldaleucel) unique for treating lymphoma?

The research provided does not contain specific information about MT-601 (Neldaleucel) for lymphoma, so I cannot determine what makes it unique compared to existing treatments. ^{6 7 8 9 10}

Eligibility Criteria

This trial is for adults over 18 with relapsed or refractory Non-Hodgkin Lymphoma who have a life expectancy of at least 12 weeks and are in relatively good health (Karnofsky/Lansky score ≥70). They must have their own cells available to create MT-601, meet blood, liver, and kidney function requirements, agree to birth control measures, and not be pregnant or breastfeeding. Those ineligible for CD19+ CAR T cell therapy may also join.

Inclusion Criteria

It's been over a week since my last cancer treatment.

I am using or willing to use effective birth control or practice abstinence.

I had partial success with CAR T cell therapy targeting CD19.

Exclusion Criteria

Pregnant or lactating patients

I have a severe infection that is causing significant symptoms.

I am currently taking corticosteroids not just for replacement.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of MT-601 to assess safety and tolerability

4-8 weeks

Multiple visits for dose administration and monitoring

Dose Expansion

Participants receive MT-601 at the determined safe dose to evaluate clinical efficacy

12 months

Regular visits for treatment and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• MT-601

Trial Overview The study tests the safety and effectiveness of MT-601 on patients with Non-Hodgkin Lymphoma that has returned or resisted treatment. It's a Phase 1 trial involving multiple centers where participants receive a flat dose of MT-601 made from their own cells to see how well it works against their lymphoma.

Participant Groups

Group I: Single Arm Study Experimental Treatment 1 Intervention

Single arm study evaluating MT-601 investigational product at 200 million cells and 400 million cells per dose

Who Is Running the Clinical Trial?

Marker Therapeutics, Inc.

Lead Sponsor

Trials

8

Recruited

450+

Findings from Research

In a study of 32 patients with nasal NK/T-cell lymphoma, an intensive combined therapy led to a complete response in 65% of cases, demonstrating significant efficacy in treating this rare and aggressive cancer.

The treatment, which included high-dose chemotherapy and radiotherapy, resulted in a 100% event-free survival rate at 5 years for those who responded completely, indicating a promising therapeutic approach for improving outcomes in a disease with historically poor prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nasal NK/T-cell lymphoma with disseminated disease treated with aggressive combined therapy. Avilés, A., Neri, N., Fernández, R., et al.[2018]

All patients with nasal natural killer/T-cell lymphoma (NNKTL) showed expression of PD-L1 in their tumor samples, indicating a potential mechanism for immune evasion.

Higher levels of soluble PD-L1 (sPD-L1) in the blood were associated with worse prognosis, suggesting that sPD-L1 could serve as a prognostic marker and that targeting the PD-1/PD-L1 pathway may be a promising immunotherapy approach for NNKTL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed death-ligand 1 and its soluble form are highly expressed in nasal natural killer/T-cell lymphoma: a potential rationale for immunotherapy. Nagato, T., Ohkuri, T., Ohara, K., et al.[2022]

In a case study of three patients with relapsed/refractory extranodal natural killer/T-cell lymphoma (ENKTL), a combination treatment of toripalimab (a PD-1 antibody), chidamide, etoposide, and thalidomide led to significant responses, with two patients achieving complete remission and one showing partial remission.

The treatment was associated with manageable side effects, primarily grade 2-3 leukocytopenia and anemia, suggesting that the PCET regimen could be a promising and tolerable option for improving outcomes in patients with R/R ENKTL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effective Treatment with PD-1 Antibody, Chidamide, Etoposide, and Thalidomide (PCET) for Relapsed/Refractory Natural Killer/T-Cell Lymphoma: A Report of Three Cases. Du, L., Zhang, L., Li, L., et al.[2020]

In a study of 107 patients with newly diagnosed extranodal NK/T-cell lymphoma (ENKTL), first-line treatment with anti-PD-1 antibody combined with asparaginase-based chemotherapy showed a higher overall response rate (86.11%) and complete remission rate (72.22%) compared to anti-PD-1 antibody alone (62.86% and 52.29%, respectively).

The pretreatment CD4/CD8 ratio greater than 0.83 was associated with better treatment response and longer progression-free survival (PFS), suggesting it could be a useful biomarker for predicting which patients will respond well to anti-PD-1 therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line immunotherapy with anti-PD-1 antibody for extranodal NK/T-cell lymphoma: A retrospective study. Wang, X., Wen, L., Liao, J., et al.[2023]

In a study of 121 high-risk diffuse large B-cell lymphoma (DLBCL) patients, higher pretreatment levels of soluble PD-1 (sPD-1) were associated with worse survival outcomes, indicating its potential as a prognostic marker.

sPD-1 levels decreased after three courses of immunochemotherapy, suggesting that monitoring sPD-1 could help assess treatment response and improve risk profiles for DLBCL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Soluble PD-1 but Not PD-L1 Levels Predict Poor Outcome in Patients with High-Risk Diffuse Large B-Cell Lymphoma. Vajavaara, H., Mortensen, JB., Leivonen, SK., et al.[2021]

Brexucabtagene autoleucel (KTE-X19) CAR T-cell therapy showed a remarkable 91% objective response rate and 68% complete response rate in 68 patients with relapsed/refractory mantle cell lymphoma after a median follow-up of 35.6 months, indicating its efficacy in this challenging patient population.

The therapy demonstrated durable long-term responses with manageable safety, as late-onset toxicities were infrequent, occurring in only 3% of patients, suggesting that KTE-X19 is a safe and effective treatment option even for those with high-risk characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-Year Follow-Up of KTE-X19 in Patients With Relapsed/Refractory Mantle Cell Lymphoma, Including High-Risk Subgroups, in the ZUMA-2 Study. Wang, M., Munoz, J., Goy, A., et al.[2023]

In a study of 57 patients with relapsed/refractory mantle cell lymphoma (MCL), lenalidomide showed a 35% overall response rate, with a median duration of response lasting 16.3 months for those who responded.

The treatment was associated with manageable side effects, primarily neutropenia (46%), thrombocytopenia (30%), and anemia (13%), indicating that lenalidomide can be an effective option for patients with advanced MCL who have undergone multiple prior therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of lenalidomide in relapsed/refractory mantle cell lymphoma: subset analysis of the NHL-003 study. Zinzani, PL., Vose, JM., Czuczman, MS., et al.[2021]

In a phase II trial involving 217 patients with relapsed or refractory aggressive non-Hodgkin's lymphoma, lenalidomide demonstrated an overall response rate of 35%, with 13% achieving complete remission and 22% achieving partial remission.

Lenalidomide was found to be well tolerated, although myelosuppression was a common side effect, particularly with grade 4 neutropenia occurring in 17% of patients, indicating that while effective, monitoring for blood-related side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An international phase II trial of single-agent lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma. Witzig, TE., Vose, JM., Zinzani, PL., et al.[2022]

Mantle cell lymphoma (MCL) has historically had poorer treatment outcomes compared to other non-Hodgkin's lymphoma subtypes, with many patients being ineligible for intensive therapies due to age and health conditions.

Current research is focusing on developing targeted therapies, such as the mTOR inhibitor temsirolimus and combination regimens with bortezomib, to improve treatment efficacy while minimizing side effects for patients with relapsed MCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current status of targeted therapies for mantle cell lymphoma. Chang, JE., Kahl, BS.[2021]

In the MCL-001 trial involving 134 patients with relapsed mantle-cell lymphoma, lenalidomide showed an overall response rate of 28%, with a median duration of response of 16.6 months, indicating its effectiveness in this heavily pretreated population.

Lenalidomide was found to have a predictable safety profile, with the most common severe side effects being neutropenia (43%) and thrombocytopenia (28%), suggesting that while it is effective, monitoring for these adverse events is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-agent lenalidomide in patients with mantle-cell lymphoma who relapsed or progressed after or were refractory to bortezomib: phase II MCL-001 (EMERGE) study. Goy, A., Sinha, R., Williams, ME., et al.[2021]

References

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

Nasal NK/T-cell lymphoma with disseminated disease treated with aggressive combined therapy. [2018]

2. Germany pubmed.ncbi.nlm.nih.gov

Programmed death-ligand 1 and its soluble form are highly expressed in nasal natural killer/T-cell lymphoma: a potential rationale for immunotherapy. [2022]

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

Effective Treatment with PD-1 Antibody, Chidamide, Etoposide, and Thalidomide (PCET) for Relapsed/Refractory Natural Killer/T-Cell Lymphoma: A Report of Three Cases. [2020]

4. England pubmed.ncbi.nlm.nih.gov

First-line immunotherapy with anti-PD-1 antibody for extranodal NK/T-cell lymphoma: A retrospective study. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Soluble PD-1 but Not PD-L1 Levels Predict Poor Outcome in Patients with High-Risk Diffuse Large B-Cell Lymphoma. [2021]

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

Three-Year Follow-Up of KTE-X19 in Patients With Relapsed/Refractory Mantle Cell Lymphoma, Including High-Risk Subgroups, in the ZUMA-2 Study. [2023]

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

Long-term follow-up of lenalidomide in relapsed/refractory mantle cell lymphoma: subset analysis of the NHL-003 study. [2021]

8. England pubmed.ncbi.nlm.nih.gov

An international phase II trial of single-agent lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma. [2022]

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

Current status of targeted therapies for mantle cell lymphoma. [2021]

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

Single-agent lenalidomide in patients with mantle-cell lymphoma who relapsed or progressed after or were refractory to bortezomib: phase II MCL-001 (EMERGE) study. [2021]