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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a stem cell transplant (Allo HCT) can cure or better control T-cell lymphoma, a type of blood cancer, while reducing the complications typically associated with transplants. It tests various methods of preparing patients for the transplant to identify those that cause fewer problems. Suitable candidates include individuals with peripheral T-cell lymphoma that hasn't responded to standard treatments. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to benefit from potentially effective new therapies.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that allogeneic hematopoietic cell transplantation (Allo HCT), tested in this trial for T-cell lymphoma, has shown promise in earlier studies. Evidence suggests that this treatment can help some patients live longer without cancer progression. Reports indicate that about 51% of patients survive for at least one year, and about 40% survive for at least three years after receiving Allo HCT. However, like many treatments, there are risks. Some studies report that around 19.6% of patients have died because their lymphoma worsened after the transplant. This means that while the treatment can be effective, significant risks exist, and each person’s experience can vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for T-Cell Lymphoma because they explore different conditioning regimens before a stem cell transplant, potentially offering better outcomes for patients. Unlike traditional high-intensity conditioning, the Reduced Intensity Conditioning (RIC) and modified RIC arms aim to minimize the harsh side effects typically associated with this process, making it more tolerable for patients while still preparing the body for the transplant. Additionally, the Immunosuppression Only Conditioning (IOC) arm focuses on reducing the immune response without a full conditioning regimen, which might help avoid some complications like graft-versus-host disease (GVHD). These innovative approaches could lead to more effective and safer transplantation options for individuals with T-Cell Lymphoma.

What evidence suggests that this trial's treatments could be effective for T-cell lymphoma?

This trial will evaluate different conditioning regimens for allogeneic hematopoietic stem cell transplant (Allo HCT) in treating peripheral T-cell lymphoma. Research has shown that Allo HCT can help treat this condition. In one study, about 33% of patients who received this treatment did not experience cancer progression for three years, indicating stable cancer in roughly one-third of patients during that period. Although risks exist, Allo HCT may offer long-term benefits for this type of lymphoma and is considered a possible cure for some patients. ^{2 3 4 6 7}

Who Is on the Research Team?

Dimana Dimitrova, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40541682/

Long-Term Outcomes After Allogeneic Hematopoietic Stem ... Among patients not in CR, outcomes were significantly better for indolent lymphoma (3-yr PFS: 56.6%), compared to aggressive (26.4%), and MCL (0 ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2666636725012205

Long-Term Outcomes After Allogeneic Hematopoietic Stem ... Despite pronounced toxicity, allo-HSCT is effective in high-risk, R/R B-NHL, with 5-yr PFS expectancy of ∼40%, and approximately one-third of long-term ...

3. nature.com nature.com/articles/s41409-025-02696-x

Allogeneic hematopoietic cell transplant in cutaneous T- ... A recent meta-analysis on allo-HCT reported 1-year and 3-year OS rates of 51% and 40%, respectively, with PFS rates of 42% at 1 year and 33% at ...

4. astctjournal.org astctjournal.org/article/S2666-6367(24)00226-4/fulltext

A US Multicenter Collaborative Study on Outcomes of ... Pts with less than CR at time of transplant had better median overall survival with allogeneic hematopoietic cell transplantation compared to ...

5. thelancet.com thelancet.com/journals/lanhae/article/PIIS2352-3026(25)00073-0/abstract

Allogeneic haematopoietic cell transplantation in ... Allogeneic haematopoietic cell transplantation (HCT) is a potentially curative therapy for peripheral T-cell lymphoma; however, to date, there are no ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8945300/

Outcome of allogeneic transplantation for mature T-cell ... Allo-HCT can provide durable PFS in patients with mature T-cell lymphoma (TCL). Outcomes of haplo-HCT were comparable to those of matched donor allo-HCT.

7. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/1708/503949/Intent-to-Treat-Allogeneic-Stem-Cell

Intent to Treat Allogeneic Stem Cell Transplantation Outcomes ... None of the 51 patients who underwent AlloSCT had pre-transplant measurable disease. Of transplanted patients, median PFS was 55.7 months and OS ...