Stem Cell Transplant for T-Cell Lymphoma

Recruiting at 1 trial location

Overseen By Dimana Dimitrova, M.D.

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Investigational agents

Disqualifiers: Active psychiatric disorder, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

330 Participants Needed

Trial Summary

What is the purpose of this trial?

Background: Lymphoma is a type of blood cancer. Blood cell transplant can cure some people with lymphoma. Researchers want to see if they can limit the complications transplant can cause. Objective: To test if a stem cell transplant can cure or control lymphoma. Also to test if new ways of getting a recipient ready for a transplant may result in fewer problems and side effects. Eligibility: Recipients: People ages 12 and older with peripheral T cell lymphoma that does not respond to standard treatments Donors: Healthy people ages 18 and older whose relative has lymphoma Design: Participants will be screened with: Physical exam Blood and urine tests Bone marrow biopsy: A needle inserted into the participant s hip bone will remove marrow. Donors will also be screened with: X-rays Recipients will also be screened with: Lying in scanners that take pictures of the body Tumor sample Donors may donate blood. They will take daily shots for 5 7 days. They will have apheresis: A machine will take blood from one arm and take out their stem cells. The blood will be returned into the other arm. Recipients will be hospitalized at least 2 weeks before transplant. They will get a catheter: A plastic tube will be inserted into a vein in the neck or upper chest. They will get antibody therapy or chemotherapy. Recipients will get the transplant through their catheter. Recipients will stay in the hospital several weeks after transplant. They will get blood transfusions. They will take drugs including chemotherapy for about 2 months. Recipients will have visits 6, 12, 18, 24 months after transplant, then once a year for 5 years. ...

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

The trial protocol does not specify whether you need to stop taking your current medications. However, it mentions that patients cannot be on other investigational agents, so it's best to discuss your current medications with the trial team.

What data supports the effectiveness of the treatment Allo HCT, Allogeneic Hematopoietic Cell Transplantation, Allo HCT, Allogeneic Stem Cell Transplant for T-Cell Lymphoma?

Research shows that Allo HCT can lead to long-term disease control in patients with T-cell lymphomas, with studies reporting 3-year overall survival rates around 59-64% and progression-free survival rates around 50-53%. This treatment is considered promising, especially for patients who have not responded to other therapies. ^{1 2 3 4 5}

Is allogeneic stem cell transplantation generally safe for humans?

Allogeneic stem cell transplantation (allo-HCT) has been used in various conditions, including T-cell lymphoma, and is generally considered safe, though it can have serious side effects like graft-versus-host disease (GVHD), where the donor cells attack the recipient's body. Some patients experience mild side effects, while others may face severe complications, and the risk of non-relapse mortality can be significant. ^{6 7 8 9 10}

How is the treatment Allo HCT different from other treatments for T-cell lymphoma?

Allo HCT (Allogeneic Hematopoietic Cell Transplantation) is unique because it uses donor stem cells to help the patient's immune system fight the lymphoma, offering a potential long-term control of the disease, especially for those who have not responded to other treatments. This approach can be effective even in patients with refractory disease or those who have failed prior autologous transplants. ^{2 4 11 12 13}

Research Team

Dimana Dimitrova, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

This trial is for people aged 12+ with a type of blood cancer called peripheral T cell lymphoma that hasn't improved with standard treatments. Healthy adults over 18 can be donors if they're related to someone with the condition. Participants need functioning major organs and a matched donor based on specific genetic markers.

Inclusion Criteria

I have a potential donor who matches me closely enough for a transplant.

My heart's pumping ability is within the required range for the study.

My PTCL is not responding to treatment or has come back, and/or I am considered for a stem cell transplant in my first remission.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Pre-Transplant Conditioning

Recipients undergo conditioning with immunosuppression or reduced-intensity chemotherapy to prepare for transplant

2 weeks

Hospitalization required

Transplantation

Recipients receive the stem cell transplant through a catheter

1 day

Hospitalization required

Post-Transplant Recovery

Recipients remain hospitalized for several weeks post-transplant for recovery and monitoring

Several weeks

Hospitalization required

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Visits at 6, 12, 18, 24 months, then annually

Treatment Details

Interventions

• Allo HCT

Trial Overview The study tests whether stem cell transplants can cure or control lymphoma, and if new preparation methods reduce complications. Recipients will undergo screening, receive chemotherapy or antibody therapy, get the transplant via catheter, and take medications post-transplant while being closely monitored.

Participant Groups

Group I: 5/ATL-RIC Arm Experimental Treatment 3 Interventions

modified Reduced Intensity Conditioning Arm for ATL patients, plus allogeneic HCT with GVHD prophylaxis

Group II: 4/mRIC Arm Experimental Treatment 3 Interventions

modified Reduced Intensity Conditioning Arm, plus allogeneic HCT with GVHD prophylaxis

Group III: 2/IOC Arm Experimental Treatment 3 Interventions

Immunosuppression Only Conditioning, plus allogeneic HCT with GVHD prophylaxis

Group IV: 1/RIC Arm Experimental Treatment 3 Interventions

Reduced Intensity Conditioning Arm, plus allogeneic HCT with GVHD prophylaxis

Group V: 3/Donor Arm Active Control 1 Intervention

Donors for Recipients in Arm 1, Arm 2, Arm 4, or Arm 5

Allo HCT is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Allogeneic Hematopoietic Cell Transplantation for:

• Peripheral T-cell lymphoma
• Other hematological malignancies

Approved in European Union as Allogeneic Hematopoietic Cell Transplantation for:

• Peripheral T-cell lymphoma
• Other hematological malignancies

Approved in Canada as Allogeneic Hematopoietic Cell Transplantation for:

• Peripheral T-cell lymphoma
• Other hematological malignancies

Approved in Japan as Allogeneic Hematopoietic Cell Transplantation for:

• Peripheral T-cell lymphoma
• Other hematological malignancies

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a pilot study involving 11 patients with adult T-cell leukaemia/lymphoma, allogeneic haematopoietic stem-cell transplantation (allo-HSCT) showed promising results, with a 1-year overall survival rate of 53% and a disease-free survival rate of 45%.

All 10 patients who survived more than 30 days after the transplant achieved complete remission, indicating that allo-HSCT can be an effective treatment option for ATL, although some patients experienced complications like graft-versus-host disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic haematopoietic stem cell transplantation for the treatment of adult T-cell leukaemia/lymphoma. Kami, M., Hamaki, T., Miyakoshi, S., et al.[2019]

A study involving 1942 adult patients with mature T-cell lymphomas showed that allogeneic hematopoietic cell transplantation (allo-HCT) can lead to durable progression-free survival (PFS), with 3-year PFS rates around 59-64% across different donor types.

The outcomes of haploidentical HCT were comparable to matched sibling and unrelated donor HCT, indicating that haplo-HCT is a viable option for patients, especially those with active disease or lower performance status, which were identified as significant predictors of poorer overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome of allogeneic transplantation for mature T-cell lymphomas: impact of donor source and disease characteristics. Hamadani, M., Ngoya, M., Sureda, A., et al.[2022]

Allogeneic hematopoietic stem-cell transplantation (HSCT) can lead to long-term remissions in patients with relapsed or refractory T-cell lymphoma, particularly in those with predominantly nodal histologies, showing a 3-year progression-free survival rate of 45%.

The study, which followed 52 patients over 12 years, found that while the overall survival rate at 3 years was 41%, there were significant risks of non-relapse mortality (27%) and relapse (43%), along with a 21% incidence of grade II-IV acute graft-versus-host disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A large single-center experience with allogeneic stem-cell transplantation for peripheral T-cell non-Hodgkin lymphoma and advanced mycosis fungoides/Sezary syndrome. Jacobsen, ED., Kim, HT., Ho, VT., et al.[2022]

In a study of 17 patients with T-cell and NK-cell lymphomas, allogeneic hematopoietic cell transplantation (allo-HCT) after nonmyeloablative conditioning showed promising outcomes, with 3-year overall and progression-free survival rates of 59% and 53%, respectively.

The study suggests that the graft-versus-T-cell lymphoma effect may contribute to long-term disease control, despite a significant incidence of graft-versus-host disease in 65% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic haematopoietic cell transplantation after nonmyeloablative conditioning in patients with T-cell and natural killer-cell lymphomas. Shustov, AR., Gooley, TA., Sandmaier, BM., et al.[2021]

In a study of 241 patients with T-cell non-Hodgkin lymphoma, autologous hematopoietic cell transplantation (autoHCT) showed better outcomes than allogeneic HCT (alloHCT), with higher rates of complete remission and better overall survival (53% at 3 years) for patients in their first complete remission.

AlloHCT had a significantly higher nonrelapse mortality rate (3.5 times higher) and was less effective for patients with heavily pretreated or refractory disease, indicating that autoHCT may be more beneficial for patients earlier in their treatment journey.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hematopoietic cell transplantation for systemic mature T-cell non-Hodgkin lymphoma. Smith, SM., Burns, LJ., van Besien, K., et al.[2022]

In a study of 30 patients who relapsed after allogeneic stem cell transplantation (allo-SCT), it was found that abnormal lymphocytes in the blood were less common compared to 49 patients who relapsed after chemotherapy, indicating a different relapse pattern post-transplant.

Relapses after allo-SCT were more likely to present as new lesions without the original tumor, particularly affecting the central nervous system, highlighting the need for improved diagnostic methods for early detection of relapsed adult T-cell leukemia-lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristic patterns of relapse after allogeneic hematopoietic SCT for adult T-cell leukemia-lymphoma: a comparative study of recurrent lesions after transplantation and chemotherapy by the Nagasaki Transplant Group. Itonaga, H., Sawayama, Y., Taguchi, J., et al.[2018]

Allogeneic stem cell transplantation (allo-SCT) was performed on 10 patients with adult T cell leukemia/lymphoma (ATL), showing a median leukemia-free survival of 17.5 months, indicating potential efficacy in improving outcomes for this aggressive cancer.

While six patients experienced acute graft-versus-host disease (GVHD), the study suggests that a controlled degree of GVHD may actually enhance survival, despite some patients facing severe complications and relapses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved outcome of adult T cell leukemia/lymphoma with allogeneic hematopoietic stem cell transplantation. Utsunomiya, A., Miyazaki, Y., Takatsuka, Y., et al.[2007]

Allogeneic hematopoietic stem cell transplantation (allo-HCT) without posttransplantation cyclophosphamide (PTCY) shows a 1-year overall survival rate of 34.5% and a 5-year rate of 17.7% in patients with adult T-cell leukemia-lymphoma (ATL), based on a retrospective study of 46 patients.

Despite these survival rates, the study highlights a concerningly high non-ATL mortality rate of 41.3% at 1 year and 55.8% at 5 years, indicating significant risks associated with this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective analysis of haplo-identical HLA-mismatch hematopoietic transplantation without posttransplantation cyclophosphamide for GVHD prophylaxis in patients with adult T-cell leukemia-lymphoma. Yoshimitsu, M., Utsunomiya, A., Fuji, S., et al.[2020]

A study updating the risk assessment for using HTLV-1-seropositive donors in allogeneic hematopoietic stem cell transplantation (allo-HCT) for aggressive adult T cell leukemia-lymphoma (ATL) found no significant difference in overall survival or mortality rates compared to HTLV-1-negative donors, suggesting that these donors may be safe to use if no alternatives are available.

The analysis included a larger number of HTLV-1-seropositive donors and longer observation periods, reinforcing the idea that the previous concerns about increased ATL-related mortality with these donors may not be justified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation for ATL with HTLV-1 Antibody-Positive Donors. Yoshimitsu, M., Fuji, S., Utsunomiya, A., et al.[2021]

In a study of 23 patients with relapsed or refractory lymphoma, allogeneic hematopoietic stem cell transplantation (Allo-HSCT) resulted in a 56.5% complete remission rate, indicating its efficacy as a salvage treatment.

The overall survival rates at 12 and 24 months were 68.6% and 59.5%, respectively, suggesting that Allo-HSCT can provide significant long-term benefits, while myeloablative conditioning regimens were found to be effective and safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic Hematopoietic Stem Cell Transplantation: A Salvage Treatment for Relapsed or Refractory Lymphoma. Wang, JS., Wang, Z., Wang, YN., et al.[2020]

Allogeneic hematopoietic cell transplantation (allo-HCT) can provide durable disease control in patients with angioimmunoblastic T-cell lymphoma (AITL), even for those who have previously failed autologous transplantation or have refractory disease, based on a study of 249 patients.

The study found a 4-year overall survival rate of 56% and a progression-free survival rate of 49%, indicating that allo-HCT can be an effective treatment option for AITL patients, despite significant risks of complications like graft-versus-host disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic hematopoietic cell transplantation provides effective salvage despite refractory disease or failed prior autologous transplant in angioimmunoblastic T-cell lymphoma: a CIBMTR analysis. Epperla, N., Ahn, KW., Litovich, C., et al.[2020]

In a study of patients with relapsed/refractory lymphoma who underwent allogeneic hematopoietic stem cell transplant (allo-HSCT) after reduced intensity conditioning, the one-year overall survival rate was 87% and the five-year rate was 79.9%, indicating favorable long-term outcomes.

The incidence of acute graft-versus-host disease (GVHD) was 48%, but only mild cases (grade I/II) were observed, suggesting that allo-HSCT can be a safe treatment option with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fludarabine-Melphalan-Campath, Followed by Unmanipulated Peripheral-Blood Haematopoietic Stem Cells, Can Still Cure Lymphoma. Avenoso, D., Alabdulwahab, A., Kenyon, M., et al.[2023]

Allogeneic stem cell transplantation (allo-SCT) shows a Graft-vs.-Lymphoma (GvL) effect, leading to lower relapse rates in patients with various types of lymphoma, particularly in slowly proliferating diseases like chronic lymphocytic leukemia and indolent lymphomas.

Despite advancements like reduced-intensity conditioning that lower transplant-related mortality, patients with Hodgkin's disease and aggressive lymphomas still face high relapse rates, indicating a need for further research and improved treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic transplantation in lymphoma: current status. Schmitz, N., Dreger, P., Glass, B., et al.[2007]

References

1. England pubmed.ncbi.nlm.nih.gov

Allogeneic haematopoietic stem cell transplantation for the treatment of adult T-cell leukaemia/lymphoma. [2019]

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

Outcome of allogeneic transplantation for mature T-cell lymphomas: impact of donor source and disease characteristics. [2022]

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

A large single-center experience with allogeneic stem-cell transplantation for peripheral T-cell non-Hodgkin lymphoma and advanced mycosis fungoides/Sezary syndrome. [2022]

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

Allogeneic haematopoietic cell transplantation after nonmyeloablative conditioning in patients with T-cell and natural killer-cell lymphomas. [2021]

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

Hematopoietic cell transplantation for systemic mature T-cell non-Hodgkin lymphoma. [2022]

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

Characteristic patterns of relapse after allogeneic hematopoietic SCT for adult T-cell leukemia-lymphoma: a comparative study of recurrent lesions after transplantation and chemotherapy by the Nagasaki Transplant Group. [2018]

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

Improved outcome of adult T cell leukemia/lymphoma with allogeneic hematopoietic stem cell transplantation. [2007]

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

A retrospective analysis of haplo-identical HLA-mismatch hematopoietic transplantation without posttransplantation cyclophosphamide for GVHD prophylaxis in patients with adult T-cell leukemia-lymphoma. [2020]

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

Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation for ATL with HTLV-1 Antibody-Positive Donors. [2021]

10. India pubmed.ncbi.nlm.nih.gov

Allogeneic Hematopoietic Stem Cell Transplantation: A Salvage Treatment for Relapsed or Refractory Lymphoma. [2020]

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

Allogeneic hematopoietic cell transplantation provides effective salvage despite refractory disease or failed prior autologous transplant in angioimmunoblastic T-cell lymphoma: a CIBMTR analysis. [2020]

12. Italy pubmed.ncbi.nlm.nih.gov

Fludarabine-Melphalan-Campath, Followed by Unmanipulated Peripheral-Blood Haematopoietic Stem Cells, Can Still Cure Lymphoma. [2023]

13. Italy pubmed.ncbi.nlm.nih.gov

Allogeneic transplantation in lymphoma: current status. [2007]