Stem Cell Transplant for T-Cell Lymphoma

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Jennifer A Kanakry, M.D.

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: National Cancer Institute (NCI)

Must not be taking: Investigational agents

Disqualifiers: Active psychiatric disorder, others

No Placebo Group

Prior Safety Data

Approved in 4 Jurisdictions

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.

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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.

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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.

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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.

Trial 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

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

National Marrow Donor Program Minneapolis, MN

National Institutes of Health Clinical Center Bethesda, MD

Who Is Running the Clinical Trial?

National Cancer Institute (NCI) Lead Sponsor

References

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

Allogeneic haematopoietic stem cell transplantation for the treatment of adult T-cell leukaemia/lymphoma. [2019] The feasibility of allogeneic haematopoietic stem-cell transplantation (allo-HSCT) in 11 patients with adult T-cell leukaemia/lymphoma (ATL) (6 acute, 4 lymphoma, 1 chronic type) was evaluated. The preparative regimens (9 conventional, 2 reduced-intensity) were tolerable. Five patients developed acute graft-versus-host disease (GVHD), and three, extensive chronic GVHD. All 10 patients who survived > 30 d achieved complete remission. Estimated 1-year overall and disease-free survival rates were 53 +/- 30% and 45 +/- 29% respectively. Four patients remain alive and disease-free at a median follow-up of 25 months. The others died of transplantation-related complications. This pilot study suggests that allo-HSCT in ATL should be evaluated further.

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] Mature T-cell lymphomas constitute the most common indication for allogeneic hematopoietic cell transplantation (allo-HCT) of all lymphomas. Large studies evaluating contemporary outcomes of allo-HCT in mature T-cell lymphomas relative to commonly used donor sources are not available. Included in this registry study were adult patients who had undergone allo-HCT for anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma (AITL), or peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) between 2008 and 2018. Hematopoietic cell transplantation (HCT) platforms compared were posttransplant cyclophosphamide-based haploidentical (haplo-)HCT, matched sibling donor (MSD) HCT, matched unrelated donor HCT with in vivo T-cell depletion (MUD TCD+), and matched unrelated donor HCT without in vivo T-cell depletion (MUD TCD-). Coprimary end points were overall survival (OS) and progression-free survival (PFS); secondary end points included nonrelapse mortality (NRM), and relapse/progression incidence (RI). A total of 1942 patients were eligible (237 haplo-HCT; 911 MSD; 468 MUD TCD+; 326 MUD TCD-). Cohorts were comparable for baseline characteristics with the exception of higher proportions of patients with decreased performance status (PS) and marrow graft recipients in the haplo-HCT group. Using univariate and multivariate comparisons, OS, PFS, RI, and NRM were not significantly different among the haplo-HCT, MSD, MUD TCD+, and MUD TCD- cohorts, with 3-year OS and PFS of 60%, 63%, 59%, and 64%, respectively, and 50%, 50%, 48%, and 52%, respectively. Significant predictors of inferior OS and PFS on multivariate analysis were active disease status at HCT and decreased PS. AITL was associated with significantly reduced relapse risk and better PFS compared with PTCL-NOS. 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.

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] The prognosis for patients with most forms of T-cell lymphoma is poor. Allogeneic hematopoietic stem-cell transplantation (HSCT) may improve the outcome.

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] Patients with T-cell and natural killer-cell lymphomas have poor outcomes. This study examined the role of allogeneic haematopoietic cell transplantation (allo-HCT) after nonmyeloablative conditioning in this setting. Seventeen patients with T-cell lymphoma or NK-cell lymphoma, including three patients in first complete remission, received allo-HCT after 2 Gy total-body irradiation and fludarabine. The median age was 57 (range, 18-73) years. The median number of prior therapies was 3 (range, 1-7), six patients (35%) had failed prior autologous HCT, and five patients (29%) had refractory disease at the time of allograft. Postgrafting immunosuppression was provided with mycophenolate mofetil with ciclosporin or tacrolimus. After a median follow-up of 3.3 (range, 0.3-8.0) years among surviving patients, the estimated probabilities of 3-year overall and progression-free survival were 59% and 53%, respectively, while the estimated probabilities of non-relapse mortality and relapse at 3 years were 19% and 26%, respectively. Sixty-five percent of patients developed grades 2-4 acute graft-versus-host disease and 53% of patients developed chronic graft-versus-host disease. Allo-HCT after nonmyeloablative conditioning is a promising salvage option for selected patients with T-cell and NK-cell lymphomas. These results suggest that graft-versus-T-cell lymphoma activity is responsible for long-term disease control.

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

Hematopoietic cell transplantation for systemic mature T-cell non-Hodgkin lymphoma. [2022] To analyze outcomes of hematopoietic cell transplantation (HCT) in T-cell non-Hodgkin lymphoma.

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] Allogeneic hematopoietic SCT (allo-SCT) is a promising therapy that may provide long-term durable remission for adult T-cell leukemia-lymphoma (ATL) patients; however, the incidence of relapse associated with ATL remains high. To determine the clinical features of these patients at relapse, we retrospectively analyzed tumor lesions in 30 or 49 patients who relapsed following allo-SCT or chemotherapy (CHT), respectively, at three institutions in Nagasaki prefecture between 1997 and 2011. A multivariate analysis revealed that the development of abnormal lymphocytes in the peripheral blood of patients at relapse was less frequent after allo-SCT than after CHT (P

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

Improved outcome of adult T cell leukemia/lymphoma with allogeneic hematopoietic stem cell transplantation. [2007] Adult T cell leukemia/lymphoma (ATL) is a poor prognosis T cell malignancy. In order to improve the outcome, we employed allogeneic stem cell transplantation (allo-SCT) for ATL in 10 patients, nine of whom were from HLA-identical siblings and one from an unrelated donor. Conditioning regimens varied among the patients except that all received total body irradiation. The patients tolerated the regimens well with mild, if any toxicity, and engraftment occurred in all cases. Median leukemia-free survival after allo-SCT was 17.5+ months (range 3.7-34.4+). Six of the 10 patients developed acute GVHD (one case each with grade I, III or IV, and three cases with grade II) and three patients developed extensive chronic GVHD. Four patients died after allo-SCT during the study period from either acute GVHD (grade IV), pneumonitis, gastrointestinal bleeding or renal insufficiency. Two of the 10 cases with no symptoms of GVHD relapsed with clinical ATL. These results strongly suggest that allo-SCT may improve the survival in ATL if a controlled degree of GVHD develops.

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] Currently, allogeneic hematopoietic stem cell transplantation (allo-HCT) is the only available curative modality for patients with adult T-cell leukemia-lymphoma (ATL). When used in conjunction with posttransplantation cyclophosphamide (PTCY) for graft-versus-host disease prophylaxis, allo-HCT from an HLA haplo-identical donor yields promising outcomes for many diseases other than ATL. However, appropriate comparisons with other donor sources, especially cord blood and conventional HLA haplo-identical donors, are needed to validate the safety and efficacy of this modality. In this study, we retrospectively evaluated the outcome of allo-HCT without PTCY in patients with ATL registered in the Japan Society for Hematopoietic Cell Transplantation TRUMP database between 1985 and 2015. During that period, 46 patients received allo-HCT without PTCY and survivors were followed for a median of 2316.5 days (range: 220-3884 days). Although the estimated 1- and 5-year overall survival rates of the entire cohort were 34.5% and 17.7%, respectively, the cumulative 1- and 5-year non-ATL mortality rates of 41.3% and 55.8%, respectively, were high. The results of our study will serve as a platform for discussions of the safety and efficacy of haplo-HCT for future clinical trials in patients with ATL.

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

Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation for ATL with HTLV-1 Antibody-Positive Donors. [2021] Allogeneic hematopoietic stem cell transplantation (allo-HCT) is the only available curative treatment option for patients with aggressive adult T cell leukemia-lymphoma (ATL). Donor human T cell leukemia virus (HTLV) 1 seropositivity is a critical concern when choosing relative donors, as they are not usually recommended due solely to the occurrence of donor-derived ATL. A previous report suggested that allo-HCT with an HTLV-1-seropositive donor increased ATL-related mortality. We updated the risk assessment for choosing an HTLV-1-seropositive allo-HCT donor for ATL. Our current registry data, which include larger numbers of HTLV-1-seropositive donors and longer observation periods, revealed no significant difference in overall survival (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.70-1.24; P = .61) or cumulative incidence of either ATL-related (HR, 0.96; 95% CI, 0.64 to 1.45; P = .80) or non-ATL-related mortality (HR, 0.91; 95% CI, 0.61 to 1.37; P = .66). Similarly, when considering only patients with ATL in complete remission, there was no significant difference in overall survival (HR, 1.02; 95% CI, 0.70 to 1.49; P = .91) or cumulative incidence of either ATL-related (HR, 1.20; 95% CI, 0.66 to 2.20; P=0.54) or non-ATL-related mortality (HR, 0.86; 95% CI, 0.52-1.42; P = .66). These data indicate that selecting HTLV-1-seropositive donors might not be contraindicated for patients with ATL receiving allo-HCT if alternative donors are unavailable. Further risk assessment remains to be performed.

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

Allogeneic Hematopoietic Stem Cell Transplantation: A Salvage Treatment for Relapsed or Refractory Lymphoma. [2020] To analyze the efficacy and safety of allogeneic hematopoietic stem cell transplantation (Allo-HSCT) in patients with relapsed or refractory lymphoma, the therapeutic efficacy, safety, and survival of 23 patients were evaluated. There were 18 (78.3 %) patients with relapsed lymphoma and 5 (21.7 %) patients with refractory lymphoma. Patients were grafted from human leukocyte antigen (HLA)-matched (10) or mismatched (7) related donors, or matched unrelated donors (6). The responses after Allo-HSCT included 13 (56.5 %) cases of complete remission, 5 (21.7 %) cases of partial remission, and 5 (21.7 %) cases of progressive disease. Overall, 16 of 23 patients were alive at a median follow up of 1,035 days (range 60-2,613), five patients died because of non-relapsed mortality, and two patients died of progressive disease. Progression-free survival rates were 64.6 and 48.4 % at 12 and 24 months, respectively, and overall survival rates were 68.6 and 59.5 % at 12 and 24 months, respectively. Allo-HSCT may be a salvage treatment for relapsed or refractory lymphoma. Myeloablative conditioning regimens may be effective and safe.

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] There is a paucity of data on the role of allogeneic hematopoietic cell transplantation (allo-HCT) in patients with angioimmunoblastic T-cell lymphoma (AITL). Using the CIBMTR registry, we report here the outcomes of AITL patients undergoing an allo-HCT.

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

Fludarabine-Melphalan-Campath, Followed by Unmanipulated Peripheral-Blood Haematopoietic Stem Cells, Can Still Cure Lymphoma. [2023] The second decade of this millennium was characterized by a widespread availability of chimeric antigen receptor T-cell (CAR-T) therapies to treat relapsed and refractory lymphomas. As expected, the role and indication of allogeneic haematopoietic stem cell transplant (allo-HSCT) in the management of lymphoma changed. Currently, a non-neglectable proportion of patients will be considered candidate for an allo-HSCT, and the debate of which transplant platform should be offered is still active.

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

Allogeneic transplantation in lymphoma: current status. [2007] Allogeneic transplantation of hematopoietic stem cells (allo-SCT) is being increasingly used to treat patients with lymphoma. We describe current results of allo-SCT in patients with Hodgkin's disease, indolent lymphoma including Waldenström's disease, and aggressive lymphoma including mantle cell lymphoma and mature T-cell lymphomas. A Graft-vs.-Lymphoma (GvL) effect is present in most entities as evidenced by the generally lower relapse rates after allo-SCT and the results of donor lymphocyte infusions. Slowly proliferating diseases like chronic lymphocytic leukemia, indolent lymphomas, and some T-cell lymphomas are particularly sensitive to the effects of allogeneic T-cells while patients with Hodgkin's disease and aggressive lymphoma may need vigorous debulking before allo-SCT to achieve optimal results. Although reduced-intensity conditioning has lowered transplant-related mortality in most and improved survival in some sub-entities, relapse rates in patients with Hodgkin's disease and aggressive B-cell lymphomas, as well as in patients with heavily pre-treated and refractory lymphoma, remain high and further improvement is undoubtedly needed. Large prospective studies in well-defined entities are necessary to further clarify the role of allo-SCT in lymphoma.