Chemotherapy + Stem Cell Transplant + Romidepsin for T-Cell Lymphoma

Recruiting at 11 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: QT prolonging drugs, CYP3A4 inhibitors

Disqualifiers: Progressive disease, Cardiac abnormalities, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

47 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking medications that cause significant QT prolongation (a heart rhythm issue) and CYP3A4 inhibitors (a type of drug that affects how your body processes certain medications).

What data supports the effectiveness of the treatment Autologous Stem Cell Transplant, High Dose Chemotherapy, and Romidepsin for T-Cell Lymphoma?

Research shows that high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is effective for aggressive lymphomas, with studies indicating improved survival rates compared to conventional chemotherapy. Specifically, ASCT has shown a complete response rate of 59% in T-cell lymphoma patients, suggesting its potential effectiveness in treating this condition. ^{1 2 3 4 5}

Is the combination of chemotherapy, stem cell transplant, and Romidepsin safe for humans?

High-dose chemotherapy with autologous stem cell transplantation (ASCT) has been used safely in various lymphoma treatments, with no toxic deaths reported in some studies. However, there can be short-term complications, and in some cases, treatment-related deaths have occurred. Romidepsin, also known as Istodax, is not specifically mentioned in the safety data provided, so its safety in combination with ASCT is not detailed here. ^{1 5 6 7 8}

How is the treatment of Chemotherapy + Stem Cell Transplant + Romidepsin for T-Cell Lymphoma different from other treatments?

This treatment is unique because it combines high-dose chemotherapy and autologous stem cell transplant (ASCT) with romidepsin, a drug that has shown effectiveness in treating T-cell lymphoma, especially in cases where other treatments have failed. Romidepsin works as a histone deacetylase inhibitor, which can help control cancer cell growth, and its combination with ASCT may offer a new approach for patients with relapsed or refractory T-cell lymphoma. ^{1 2 4 9 10}

What is the purpose of this trial?

The purpose of this study is to test the benefit of a chemotherapy drug called romidepsin in patients with T Cell Non-Hodgkin Lymphoma (T NHL) who have undergone autologous transplantation.

Research Team

Steven Horowitz, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for patients over 16 with T Cell Non-Hodgkin Lymphoma who are eligible for a stem cell transplant. They must have collected enough stem cells, be in remission after chemotherapy, and have normal liver function tests. Excluded are those with progressive disease, previous transplants, active severe infections including HIV, inadequate organ function or performance status, pregnancy or breastfeeding without contraception use, prior romidepsin therapy, CNS involvement by cancer, certain heart conditions or arrhythmias.

Inclusion Criteria

I am over 16 and approved for a transplant by my doctor.

I have been diagnosed with a specific type of T-cell lymphoma.

Stem cell collection: A minimum of 2 x 10^6 CD34+ cells must have been collected

Exclusion Criteria

My health is too poor for standard treatments.

I have been treated with romidepsin before.

My cancer has spread to my brain or its coverings.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

High Dose Chemotherapy and Autologous Stem Cell Transplant

Participants receive high dose chemotherapy followed by autologous stem cell transplant

4-6 weeks

Maintenance Therapy

Participants receive maintenance therapy with Romidepsin

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Treatment Details

Interventions

• Autologous Stem Cell Transplant
• High Dose Chemotherapy
• Romidepsin

Trial Overview The study is testing the effectiveness of romidepsin as maintenance therapy following high-dose chemotherapy and autologous stem cell transplant in patients with T Cell Non-Hodgkin Lymphoma. Romidepsin will be administered to see if it can help keep the lymphoma from coming back after the transplant.

Participant Groups

Group I: high dose chemo w/asct + maintenance txt Experimental Treatment 1 Intervention

High dose chemotherapy (Carmustine), VP-16 (etoposide, Vepesid®), Cytarabine (Ara-C), Melphalan (Alkeran)with autologous stem cell transplant followed by maintenance therapy with Romidepsin (Istodax)

Autologous Stem Cell Transplant is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Autologous Stem Cell Transplant for:

• Multiple Myeloma
• Non-Hodgkin Lymphoma
• Hodgkin Lymphoma
• Leukemia

Approved in European Union as Autologous Stem Cell Transplant for:

• Multiple Myeloma
• Non-Hodgkin Lymphoma
• Hodgkin Lymphoma
• Leukemia

Approved in Canada as Autologous Stem Cell Transplant for:

• Multiple Myeloma
• Non-Hodgkin Lymphoma
• Hodgkin Lymphoma
• Leukemia

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

University of Washington

Collaborator

Trials

1,858

Recruited

2,023,000+

H. Lee Moffitt Cancer Center and Research Institute

Collaborator

Trials

576

Recruited

145,000+

Weill Medical College of Cornell University

Collaborator

Trials

1,103

Recruited

1,157,000+

Findings from Research

In a study of 15 patients with relapsed or refractory diffuse large B-cell lymphoma, administering CD19-specific CAR T cells after high-dose chemotherapy and autologous stem cell transplantation resulted in a 2-year progression-free survival rate of 30%.

The treatment was associated with a high incidence of reversible neurotoxicity and cytokine release syndrome, but patients with lower levels of naive-like CD4+ and CD8+ CAR T cells showed better disease control, indicating that the immunophenotype of CAR T cells may influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19 CAR T cells following autologous transplantation in poor-risk relapsed and refractory B-cell non-Hodgkin lymphoma. Sauter, CS., Senechal, B., Rivière, I., et al.[2021]

In a randomized phase III study involving 421 patients with untreated peripheral T-cell lymphoma (PTCL), the combination of romidepsin and CHOP (Ro-CHOP) did not significantly improve progression-free survival (PFS) or overall survival compared to CHOP alone.

The Ro-CHOP treatment resulted in a higher incidence of severe side effects, such as thrombocytopenia and neutropenia, indicating that while romidepsin was added to the regimen, it did not provide a meaningful benefit and increased the risk of adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Romidepsin Plus CHOP Versus CHOP in Patients With Previously Untreated Peripheral T-Cell Lymphoma: Results of the Ro-CHOP Phase III Study (Conducted by LYSA). Bachy, E., Camus, V., Thieblemont, C., et al.[2023]

References

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

Intermediate doses of cytarabine plus granulocyte-colony-stimulating factor as an effective and safe regimen for hematopoietic stem cell collection in lymphoma patients with prior mobilization failure. [2019]

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

Comparison of high-dose therapy and autologous bone marrow transplantation for T-cell and B-cell non-Hodgkin's lymphomas. [2021]

3. England pubmed.ncbi.nlm.nih.gov

High-dose treatment with autologous stem cell transplantation versus sequential chemotherapy: the GELA experience. [2008]

4. Greece pubmed.ncbi.nlm.nih.gov

Myelosuppression After Radiation Therapy in Patients With and Without Autologous Peripheral Blood Stem Cell Transplantation: A Retrospective Observational Study. [2019]

5. Slovakia pubmed.ncbi.nlm.nih.gov

Autologous stem cell transplantation in first-line treatment of high-risk aggressive non-Hodgkin's lymphoma. [2015]

6. England pubmed.ncbi.nlm.nih.gov

High-dose therapy and autologous stem cell transplantation in relapsing cutaneous lymphoma. [2004]

7. Serbia pubmed.ncbi.nlm.nih.gov

[Autologous stem cell transplantation in the treatment of Hodgkin's disease]. [2019]

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

CD19 CAR T cells following autologous transplantation in poor-risk relapsed and refractory B-cell non-Hodgkin lymphoma. [2021]

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

Romidepsin Plus CHOP Versus CHOP in Patients With Previously Untreated Peripheral T-Cell Lymphoma: Results of the Ro-CHOP Phase III Study (Conducted by LYSA). [2023]

10. Japan pubmed.ncbi.nlm.nih.gov

Romidepsin-induced durable remission for relapsed nodal peripheral T-cell lymphoma with T follicular helper phenotype after allogeneic hematopoietic cell transplantation. [2023]