CHO-H01 for Lymphoma

Recruiting at 5 trial locations

Overseen By Tanny Tsao

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Cho Pharma Inc.

Must not be taking: PD-L1, PD-1, CTLA-4, Corticosteroids

Disqualifiers: HIV, Hepatitis B, Hepatitis C, others

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

Compensation: Varies

Number of Visits: Unknown

37 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop any anti-CD20 treatments for at least 30 days before starting CHO-H01. If you are taking systemic corticosteroids, you must not exceed a daily dose of 15 mg prednisone or equivalent within 14 days before starting the trial. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

What data supports the effectiveness of the drug CHO-H01 for treating lymphoma?

Research on similar treatments, like the CD30-targeted drug brentuximab vedotin and PD-1 antibodies such as nivolumab, shows they are effective in treating Hodgkin lymphoma, especially in cases where the disease has returned or resisted other treatments. These drugs have shown promising results in improving cure rates and reducing long-term side effects. ^{1 2 3 4 5}

What safety data exists for CHO-H01 (PD-1 inhibitors) in humans?

PD-1 inhibitors, used in treating relapsed or refractory classical Hodgkin lymphoma, have shown a generally favorable safety profile. Common side effects include mild to moderate immune-related reactions like fever, skin issues, and gastrointestinal problems, which were resolved in all patients. Serious side effects are rare, and no deaths were directly linked to the treatment. ^{6 7 8 9 10}

How does the drug CHO-H01 differ from other treatments for lymphoma?

CHO-H01 is unique because it may involve targeting the PD-1/PD-L1 pathway, which is a mechanism used by some immune checkpoint inhibitors to treat relapsed or refractory classic Hodgkin's lymphoma by enhancing the body's immune response against cancer cells. ^{1 11 12 13 14}

What is the purpose of this trial?

This trial tests CHO-H01, a new drug for non-Hodgkin's lymphoma, in patients whose cancer has returned or didn't respond to other treatments. The drug is given through an IV and targets cancer cells with a specific marker to destroy them.

Eligibility Criteria

This trial is for adults with a specific BMI range who have relapsed or refractory CD20+ non-Hodgkin's lymphoma. They should be relatively active (ECOG 0-2), have measurable cancer, and not received certain treatments recently. Participants need good heart function, agree to birth control if applicable, and expect to live more than 12 weeks.

Inclusion Criteria

Your body mass index (BMI) should be between 18 and 32 kg/m2.

Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

Phase I: Have histologically confirmed CD20 + non-Hodgkin's lymphoma according to the World Health Organization's 2016 classification: Low grade lymphoma: follicular lymphoma (Grades 1-3a), marginal zone lymphoma, small lymphocytic lymphoma; Other lymphoma: DLBCL (NOS: to include germinal center B-cell-like [GCB] and activated B-cell-like [ABC]), follicular lymphoma Grade 3b, mantel cell lymphoma; primary mediastinal large B-cell lymphoma.

Exclusion Criteria

Must not have any known or current illnesses (such as autoimmune disease, unless well controlled or resolved), infection, or other condition that could limit study compliance or interfere with assessments

Subjects with known hepatitis B surface antigen (HBsAg) seropositive or known or suspected active hepatitis C infection with detectable viral load

Subjects who have received (or are receiving) systemic corticosteroids: At a daily dose higher than 15 mg prednisone or equivalent within 14 days prior to the first administration of CHO-H01; Topical, inhaled, nasal, and ophthalmic steroids are allowed

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Dose escalation phase with CHO-H01 administered via IV infusion once weekly for 4 weeks in Cycle 1 and then once only on Day 1 in each subsequent 21-day cycle until disease progression or for up to 6 cycles

19 weeks

Phase 2a Treatment

Assessment of anticancer activity and safety of CHO-H01 plus lenalidomide in low-grade relapsed/refractory CD20+ non-Hodgkin's lymphoma

16 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• CHO-H01

Trial Overview CHO-H01 is being tested in two parts: first to find the safest dose and then to see how well it works against the cancer. It's for those whose lymphoma has returned or didn't respond after treatment.

Participant Groups

Group I: CHO-H01+Lenalidomide Experimental Treatment 2 Interventions

Expansion phase with lenalidomide combination. Phase2a: Single cohort at Recommended Phase 2 Dose (RP2D) of CHO-H01.

Group II: CHO-H01 Experimental Treatment 1 Intervention

Dose escalation phase Phase 1: Five to six cohorts of escalating dose levels of CHO-H01 from 0.5mg/kg to 12 mg/kg.

Who Is Running the Clinical Trial?

Cho Pharma Inc.

Lead Sponsor

Trials

2

Recruited

60+

Findings from Research

Hodgkin's lymphoma (HL) has become one of the most curable cancers in adults, with about 80% of patients achieving long-term disease-free survival due to substantial clinical advancements.

Current treatment strategies focus on enhancing chemotherapy and radiotherapy effectiveness while reducing side effects, with ongoing trials exploring lower doses and smaller radiation fields, as well as more intense drug combinations for high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line treatment of Hodgkin's lymphoma. Klimm, B., Engert, A., Diehl, V.[2007]

Brentuximab vedotin, a CD30 antibody-drug conjugate, and PD-1 antibodies like nivolumab and pembrolizumab are highly effective treatments for relapsed and refractory classical Hodgkin lymphoma (cHL), showing promising results in ongoing studies for earlier treatment lines.

These targeted therapies are expected to improve cure rates and decrease long-term toxicity compared to traditional chemotherapy and radiotherapy, potentially transforming the management of cHL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in CD30- and PD-1-targeted therapies for classical Hodgkin lymphoma. Wang, Y., Nowakowski, GS., Wang, ML., et al.[2020]

In a study of 263 patients with classical Hodgkin lymphoma (CHL), 28.1% were found to be CD20-positive, which was significantly associated with higher rates of Epstein-Barr virus (EBV) infection and specific CHL subtypes, indicating a potential link between CD20 expression and disease characteristics.

CD20 positivity, along with EBV infection, was correlated with poorer progression-free survival (PFS), particularly in patients not receiving local radiotherapy, suggesting that CD20 expression may influence prognosis through its relationship with EBV infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical features and prognosis of CD20-positive classical Hodgkin lymphoma]. Qin, Y., Kang, SY., He, XH., et al.[2018]

Nivolumab, a PD1 blocking antibody, shows a high overall objective response rate of 68% in patients with relapsed or refractory classic Hodgkin's lymphoma, indicating its efficacy as a treatment option.

The study suggests that nivolumab has a controllable safety profile, making it a viable long-term treatment alternative compared to traditional therapies for Hodgkin's lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of nivolumab as checkpoint inhibitor drug on survival rate of patients with relapsed/refractory classical Hodgkin lymphoma: a meta-analysis of prospective clinical study. Amraee, A., Evazi, MR., Shakeri, M., et al.[2022]

Hodgkin lymphoma (HL) generally has a good prognosis with standard chemotherapy and radiation, but patients with relapsed or refractory disease face poorer outcomes, highlighting the need for new treatment options.

Novel therapies, including antibody-drug conjugates targeting CD30 and immune checkpoint inhibitors, are showing promise in treating HL, and ongoing trials are investigating their use in combination with existing chemotherapy regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel agents in the therapy of Hodgkin lymphoma. Ansell, S.[2018]

In a retrospective analysis of 66 patients with relapsing refractory classical Hodgkin's lymphoma (cHL) treated with PD-1 inhibitors, the overall response rate was 70%, with 47% achieving complete remission and 23% partial remission, indicating strong efficacy in a real-world setting.

The treatment was well-tolerated, with immune-related adverse events mostly being mild (grades 1-2), and no deaths attributed to the therapy, suggesting a favorable safety profile alongside a median overall survival of 65% at 5 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A real-world analysis of PD1 blockade from the Rete Ematologica Pugliese (REP) in patients with relapse/refractory Hodgkin's lymphoma. Gaudio, F., Loseto, G., Bozzoli, V., et al.[2023]

Anti-PD1 antibodies, such as nivolumab and pembrolizumab, have been approved for treating relapsed or refractory classical Hodgkin lymphoma (cHL) due to their high response rates and favorable safety profiles.

This review highlights the importance of immune checkpoint inhibitors in overcoming cancer's ability to evade the immune system, and discusses ongoing clinical trials and potential combination therapies to enhance treatment efficacy in cHL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Checkpoint Inhibition in Hodgkin Lymphoma - a Review. Bröckelmann, PJ., Engert, A.[2018]

In a study of 260 patients with relapsed or refractory classical Hodgkin lymphoma treated with anti-PD-1 therapies, the 3-year progression-free survival rate was 55.1% and the overall survival rate was 89.7%, indicating good long-term outcomes for responders.

Patients who achieved complete remission had significantly better survival rates compared to those with partial remission, highlighting that the extent of response to treatment is crucial for long-term success and suggesting the need for additional treatment strategies for those with partial responses or refractory disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term survival benefit of anti-PD-1 therapy in patients with relapsed or refractory classical Hodgkin lymphoma. Liu, W., Lin, N., Feng, X., et al.[2023]

Anti-PD-1 monoclonal antibodies have shown a high response rate and an acceptable safety profile in patients with relapsed or refractory classic Hodgkin lymphoma (cHL), but most patients eventually relapse after treatment.

Using anti-PD-1 mAbs as bridging therapy before allogeneic hematopoietic cell transplantation (allo-HCT) can be feasible, although it may increase the risk of severe graft-versus-host disease (GVHD); however, survival outcomes remain favorable, especially with posttransplant cyclophosphamide-based GVHD prophylaxis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-programmed cell death-1 monoclonal antibody therapy before or after allogeneic hematopoietic cell transplantation for classic Hodgkin lymphoma: a literature review. Ito, A., Kim, SW., Fukuda, T.[2022]

In a study of 35 patients with relapse/refractory classical Hodgkin's lymphoma, PD-1 inhibitors showed an overall response rate of 80%, with a complete response rate of 62.9%, indicating strong efficacy both as monotherapy and in combination with chemotherapy.

Patients receiving PD-1 inhibitors combined with chemotherapy had higher response rates (94.4% overall response) and those who underwent autologous stem cell transplantation after PD-1 therapy had significantly improved progression-free survival rates (100% vs 53.5%), suggesting that this treatment strategy can enhance long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of programmed death-1 inhibitor in the treatment of relapsed/refractory classical Hodgkin's lymphoma]. Shan, DD., Liu, HM., Liu, W., et al.[2023]

In a meta-analysis of 9 clinical trials involving 731 patients with relapsed or refractory classic Hodgkin's lymphoma, PD-1 inhibitors showed a high overall response rate of 74%, indicating their efficacy in treating this type of cancer.

The treatment was associated with manageable safety profiles, with only 21% of patients experiencing grade ≥3 adverse events, suggesting that PD-1 inhibitors are a tolerable option for patients with cHL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy in Relapsed or Refractory Classic Hodgkin's Lymphoma Treated with PD-1 Inhibitors: A Meta-Analysis of 9 Prospective Clinical Trials. Zhang, X., Chen, L., Zhao, Y., et al.[2022]

The study identifies a strong association between PD-L1 expression and lymphocyte-depleted classic Hodgkin lymphoma (LD-CHL), providing a clearer diagnostic framework for this previously difficult-to-diagnose condition.

Two case studies of elderly patients with LD-CHL revealed unique tumor characteristics and immunohistochemical profiles, but both patients were too frail for treatment and succumbed to the disease within 1 to 15 months, highlighting the aggressive nature of this lymphoma in immunocompromised individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lymphocyte-depleted classic Hodgkin lymphoma with primary extranodal disease: Two cases that highlight the combination of immunodeficiency and immune escape in the pathogenesis. Tsuyuki, Y., Kohno, K., Inagaki, Y., et al.[2021]

In a study of 44 bone marrow biopsies from patients with newly diagnosed classic Hodgkin lymphoma (CHL), PD-L1 expression was found to be a highly sensitive marker for detecting bone marrow involvement, with 100% positivity in cases confirmed to have CHL.

PD-L1 staining can aid in diagnosing CHL, especially in challenging cases where Reed-Sternberg cells are sparse, as it was effective in identifying involvement even in previously nondiagnostic biopsies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-L1 Immunohistochemistry Highlights Bone Marrow Involvement by Classic Hodgkin Lymphoma in Staging Biopsies: Implications for Diagnosis and Tumor Microenvironment Alterations. Xing, W., Mai, N., Dresser, K., et al.[2020]

In a study of 25 patients with relapsed/refractory classical Hodgkin lymphoma, 68% had unsatisfactory responses to anti-PD1 therapy, but subsequent salvage chemotherapy resulted in a 60% overall response rate, indicating that chemotherapy can be effective after PD1 blockade failure.

The median progression-free survival after salvage treatment was 19.1 months, significantly longer than the 8.2 months observed after anti-PD1 therapy, suggesting that chemotherapy can improve outcomes for patients who do not respond to PD1 inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of chemotherapy after anti-PD-1 blockade failure for relapsed and refractory Hodgkin lymphoma. Casadei, B., Argnani, L., Morigi, A., et al.[2021]

References

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

First-line treatment of Hodgkin's lymphoma. [2007]

2. England pubmed.ncbi.nlm.nih.gov

Advances in CD30- and PD-1-targeted therapies for classical Hodgkin lymphoma. [2020]

3. China pubmed.ncbi.nlm.nih.gov

[Clinical features and prognosis of CD20-positive classical Hodgkin lymphoma]. [2018]

4. Italy pubmed.ncbi.nlm.nih.gov

Efficacy of nivolumab as checkpoint inhibitor drug on survival rate of patients with relapsed/refractory classical Hodgkin lymphoma: a meta-analysis of prospective clinical study. [2022]

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

Novel agents in the therapy of Hodgkin lymphoma. [2018]

6. Germany pubmed.ncbi.nlm.nih.gov

A real-world analysis of PD1 blockade from the Rete Ematologica Pugliese (REP) in patients with relapse/refractory Hodgkin's lymphoma. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Checkpoint Inhibition in Hodgkin Lymphoma - a Review. [2018]

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

Long-term survival benefit of anti-PD-1 therapy in patients with relapsed or refractory classical Hodgkin lymphoma. [2023]

9. Japan pubmed.ncbi.nlm.nih.gov

Anti-programmed cell death-1 monoclonal antibody therapy before or after allogeneic hematopoietic cell transplantation for classic Hodgkin lymphoma: a literature review. [2022]

10. China pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of programmed death-1 inhibitor in the treatment of relapsed/refractory classical Hodgkin's lymphoma]. [2023]

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

Safety and Efficacy in Relapsed or Refractory Classic Hodgkin's Lymphoma Treated with PD-1 Inhibitors: A Meta-Analysis of 9 Prospective Clinical Trials. [2022]

12. Japan pubmed.ncbi.nlm.nih.gov

Lymphocyte-depleted classic Hodgkin lymphoma with primary extranodal disease: Two cases that highlight the combination of immunodeficiency and immune escape in the pathogenesis. [2021]

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

PD-L1 Immunohistochemistry Highlights Bone Marrow Involvement by Classic Hodgkin Lymphoma in Staging Biopsies: Implications for Diagnosis and Tumor Microenvironment Alterations. [2020]

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

Effectiveness of chemotherapy after anti-PD-1 blockade failure for relapsed and refractory Hodgkin lymphoma. [2021]