HSCT for Leukemia and Lymphoma

Overseen By Tamy Grainger

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Masonic Cancer Center, University of Minnesota

Disqualifiers: Active CNS malignancy, uncontrolled infection, 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

300 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a special type of stem cell transplant, known as Hematopoietic Stem Cell Transplantation (HSCT), to treat certain blood cancers like leukemia and lymphoma. Researchers aim to determine if this treatment can benefit patients in remission but still at high risk of cancer recurrence. The trial compares two preparation methods for the transplant: one using radiation and one without. Individuals in remission, yet likely to experience a cancer return, might be suitable candidates, especially if they have specific types of leukemia or lymphoma. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research shows that both TBI (total body irradiation) and Non-TBI (non-total body irradiation) treatments used in stem cell transplants are generally safe for patients. Studies have found that TBI treatment can improve survival rates. Specifically, one study showed a one-year survival rate of 77.9% with TBI compared to 62.0% with chemotherapy, with fewer relapses. This indicates that TBI treatment is usually well-tolerated.

For Non-TBI treatment, research suggests it is a good alternative. It is similarly safe and effective, particularly for certain types of leukemia and lymphoma. Both treatments are considered potential cures for patients in remission from blood cancers like acute lymphoblastic leukemia (ALL).

Overall, these studies support the safety and effectiveness of both treatment options. However, as with any medical treatment, individual experiences may vary, so discussing potential risks with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they explore different conditioning regimens for hematopoietic stem cell transplantation (HSCT) in leukemia and lymphoma. Unlike traditional approaches that often use total body irradiation (TBI), one arm of this trial focuses on a non-TBI regimen, which could reduce the side effects typically associated with radiation, such as damage to healthy tissues. The TBI regimen, on the other hand, might offer enhanced eradication of cancer cells before transplantation. This dual approach allows researchers to compare the effectiveness and safety of these regimens, potentially leading to more tailored and less harmful treatment options for patients.

What evidence suggests that this trial's treatments could be effective for leukemia and lymphoma?

This trial compares two approaches to stem cell transplantation for leukemia and lymphoma. One treatment arm uses donor stem cell transplants with full-body radiation (TBI Regimen). Research has shown that this method can be very effective, often reducing the chance of cancer returning and improving survival rates compared to other treatments.

The other treatment arm involves stem cell transplants without full-body radiation (Non-TBI Regimen). This approach is also promising, having shown similar results for certain groups, such as children, and may cause fewer long-term side effects. Solid research supports both methods, and this trial tests their effectiveness in treating blood cancers. ^{5 6 7 8 9}

Who Is on the Research Team?

Punita Grover, MD

Principal Investigator

Masonic Cancer Center, University of Minnesota

Are You a Good Fit for This Trial?

This trial is for people with various blood disorders like leukemia, lymphoma, and myelodysplasia who are in remission or have high-risk features. They must be under 60 years old with good organ function and HIV+ patients need an undetectable viral load. Pregnant women, those with active infections or certain types of cancer that aren't responding to treatment can't join.

Inclusion Criteria

My cancer has high-risk genetic features.

My blood disorder is at an intermediate or high risk level, with less than 10% of blasts in my bone marrow.

My kidney function is within the required range for the study.

Exclusion Criteria

My condition is chronic myeloid leukemia in its advanced stage.

My scans show my cancer is getting worse, but PET scan activity alone doesn’t disqualify me.

I had a bone marrow transplant within the last 6 months if I'm under 18, or any type if I'm older.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Myeloablative Preparative Regimen

Participants undergo a myeloablative preparative regimen using either total body irradiation (TBI) or fludarabine/busulfan for those unable to receive further radiation

1-2 weeks

Transplantation and GVHD Prophylaxis

Participants receive allogeneic hematopoietic stem cell transplant followed by post-transplant GVHD prophylaxis with cyclophosphamide, tacrolimus, and mycophenolate mofetil

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of acute and chronic GVHD, relapse, and survival

2 years

What Are the Treatments Tested in This Trial?

Interventions

• HSCT with Non-TBI Regimen
• HSCT with TBI Regimen

Trial Overview The study tests a bone marrow transplant (HSCT) using either total body irradiation (TBI) or a chemo regimen for those who can't have more radiation. It's followed by drugs to prevent graft-versus-host disease. The goal is to see how well these treatments work for severe blood disorders.

How Is the Trial Designed?

Group I: TBI Regimen Experimental Treatment 1 Intervention

Group II: Non-TBI Regimen Experimental Treatment 1 Intervention

HSCT with Non-TBI Regimen is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Allo-HSCT for:

• Acute Leukemia
• Chronic Leukemia
• Hodgkin's Lymphoma
• Non-Hodgkin's Lymphoma
• Multiple Myeloma
• Myelodysplastic Syndromes
• Aplastic Anemia
• Bone Marrow Failure Syndromes
• Hemoglobinopathies
• Immune Deficiencies

Approved in United States as Allo-HSCT for:

• Acute Leukemia
• Chronic Leukemia
• Hodgkin's Lymphoma
• Non-Hodgkin's Lymphoma
• Multiple Myeloma
• Myelodysplastic Syndromes
• Aplastic Anemia
• Bone Marrow Failure Syndromes
• Hemoglobinopathies
• Immune Deficiencies

Approved in Canada as Allo-HSCT for:

• Acute Leukemia
• Chronic Leukemia
• Hodgkin's Lymphoma
• Non-Hodgkin's Lymphoma
• Multiple Myeloma
• Myelodysplastic Syndromes
• Aplastic Anemia
• Bone Marrow Failure Syndromes
• Hemoglobinopathies
• Immune Deficiencies

Approved in Japan as Allo-HSCT for:

• Acute Leukemia
• Chronic Leukemia
• Hodgkin's Lymphoma
• Non-Hodgkin's Lymphoma
• Multiple Myeloma
• Myelodysplastic Syndromes
• Aplastic Anemia
• Bone Marrow Failure Syndromes
• Hemoglobinopathies
• Immune Deficiencies

Who Is Running the Clinical Trial?

Masonic Cancer Center, University of Minnesota

Lead Sponsor

Trials

285

Recruited

15,700+

Published Research Related to This Trial

In a study involving 5,629 pediatric patients with acute lymphoblastic leukemia (ALL), total body irradiation (TBI)-based conditioning regimens before allogeneic hematopoietic stem cell transplant (HSCT) showed significantly better overall survival and event-free survival compared to chemotherapy (CHT) alone.

Both TBI and CHT conditioning had similar risks for complications like acute graft-versus-host disease and nonrelapse mortality, indicating that while TBI is more effective, it does not increase the risk of severe side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Total Body Irradiation Versus Chemotherapy Conditioning in Pediatric Acute Lymphoblastic Leukemia Patients Undergoing Hematopoietic Stem Cell Transplant: A Systematic Review and Meta-Analysis. Rehman, MEU., Chattaraj, A., Mahboob, A., et al.[2023]

A systematic review of 8 studies involving over 5000 patients indicates that total body irradiation (TBI)-based conditioning regimens for allogeneic hematopoietic cell transplantation (allo-HCT) in acute lymphoblastic leukemia (ALL) patients significantly improve overall survival (OS) and progression-free survival (PFS) while reducing relapse rates compared to chemotherapy-only regimens.

While TBI-based regimens do not increase the risk of nonrelapse mortality or lower-grade graft-versus-host disease (GVHD), they are associated with a higher risk of severe acute GVHD, suggesting a need for careful patient selection and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Total Body Irradiation-Based Myeloablative Conditioning Regimens in Patients with Acute Lymphoblastic Leukemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation: Systematic Review and Meta-Analysis. Khimani, F., Dutta, M., Faramand, R., et al.[2021]

Allogeneic hematopoietic stem cell transplantation (HSCT) can lead to long-term survival in patients with relapsed or refractory Hodgkin's or non-Hodgkin's lymphomas, particularly when autologous HSCT is not effective.

The treatment's efficacy is partly due to the graft-versus-lymphoma (GVL) effect, although this can come with significant risks like graft-versus-host disease; thus, careful patient selection based on factors like tumor type and response to previous treatments is crucial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic hematopoietic stem cell transplantation for lymphoma. Dean, RM., Bishop, MR.[2019]

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) was performed on 10 patients with T cell Lymphoblastic lymphoma (T-LBL), resulting in a 70% overall survival rate and a 70% disease-free survival rate after a median follow-up of 26 months.

Despite the promising survival outcomes, T-LBL patients experienced a high relapse rate of 10%, and complications such as acute graft versus host disease (GVHD) occurred in 5 patients, highlighting the need for careful monitoring post-transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Allogeneic Hematopoietic Stem Cell Transplantation for Treatment of T Cell Lymphoblastic Lymphoma - Clinical observation of 10 Cases]. Gong, F., Chen, H., Zhao, LY., et al.[2018]

In a pilot study involving 10 patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), intensity-modulated radiation therapy total body irradiation (IMRT-TBI) was found to be well tolerated, with all patients experiencing early adverse events but no severe complications (grade III-IV acute graft-versus-host disease).

All patients achieved neutrophil engraftment and remained alive and disease-free at the final follow-up, suggesting that IMRT-TBI is a safe option for myeloablative conditioning in allo-HSCT, warranting further investigation for long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of total body irradiation using intensity-modulated radiation therapy by helical tomotherapy in allogeneic hematopoietic stem cell transplantation: a prospective pilot study. Konishi, T., Ogawa, H., Najima, Y., et al.[2021]

In a study of 14,371 patients from the German Stem Cell Transplantation Registry, only about 10% of patients undergoing autologous hematopoietic stem cell transplantation (HSCT) received total-body irradiation (TBI), indicating its limited role in this setting.

Conversely, TBI was utilized in approximately 50% of patients undergoing allogeneic HSCT, particularly for conditions like acute lymphocytic leukemia (85%), highlighting its acceptance and importance in this treatment context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Total-body irradiation--role and indications: results from the German Registry for Stem Cell Transplantation (DRST). Heinzelmann, F., Ottinger, H., Müller, CH., et al.[2019]

In a study of 285 patients who underwent total body irradiation (TBI) before allogeneic stem cell transplantation, the overall survival rates were 72.6% at 1 year and 51.6% at 10 years, indicating that TBI is an effective treatment despite concerns about long-term complications.

A higher TBI dose of 8 Gy or more was linked to better event-free and overall survival, while lower doses and a diagnosis of acute myeloid leukemia were associated with increased rates of secondary malignancies, suggesting that careful dosing is important for optimizing outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Twenty years of experience of a tertiary cancer center in total body irradiation with focus on oncological outcome and secondary malignancies. Sieker, K., Fleischmann, M., Trommel, M., et al.[2022]

In a study of 1875 adult patients who underwent unrelated bone marrow transplantation, the cyclophosphamide/total body irradiation (Cy-TBI) regimen showed significantly better outcomes in terms of engraftment success and overall survival compared to the busulfan and cyclophosphamide (Bu-Cy) regimen.

While the Bu-Cy regimen with total lymphoid irradiation (Bu-Cy-TLI) reduced relapse rates, it was associated with higher nonrelapse mortality, indicating a trade-off between relapse prevention and overall safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of conditioning regimen on the outcome of bone marrow transplantation from an unrelated donor. Kanda, Y., Sakamaki, H., Sao, H., et al.[2019]

A study comparing pediatric patients with acute lymphoblastic leukemia (ALL) with and without central nervous system (CNS) involvement showed that a non-total body irradiation (TBI) conditioning regimen resulted in similar 5-year relapse rates, disease-free survival, and overall survival for both groups, indicating its efficacy.

Despite a higher transplantation-related mortality in CNS- patients, the differences were not statistically significant, suggesting that TBI-free allogeneic hematopoietic stem cell transplantation (HSCT) is a feasible and effective option for treating ALL patients with CNS involvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome Analysis of Pediatric Patients with Acute Lymphoblastic Leukemia Treated with Total Body Irradiation-Free Allogeneic Hematopoietic Stem Cell Transplantation: Comparison of Patients with and Without Central Nervous System Involvement. Hamidieh, AA., Monzavi, SM., Kaboutari, M., et al.[2018]

In a study of 119 adult patients with acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation, the TBI/Cy conditioning regimen resulted in a median overall survival of 11 months, compared to 6.2 months for the Bu/Cy regimen.

Although both conditioning regimens showed no statistically significant differences in overall survival and disease-free survival, the Bu/Cy regimen was associated with a higher risk of relapse, indicating a potential disadvantage in using this non-TBI approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irradiation free conditioning regimen is associated with high relapse rate in Egyptian patients with acute lymphoblastic leukemia following allogeneic hematopoietic stem cell transplantation. Abdelaty, MM., Gawaly, A., Fathy, GM., et al.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38716596/

[Efficacy of allogeneic hematopoietic stem cell ... Objective: To analyze the efficacy of allo-HSCT with total body irradiation (TBI) and chemotherapy alone in the treatment of adult ALL and ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0145212623006811

A comprehensive comparison between TBI vs non ... Non-TBI conditioning is an alternative modality in treating pediatric ALL patients as it has demonstrated latent toxicity and more favorable OS rates.

3. astctjournal.org astctjournal.org/article/S1083-8791(17)30691-2/fulltext

Outcome Analysis of Pediatric Patients with Acute ... These findings suggest that HSCT using a non–TBI-containing conditioning regimen can lead to similar outcomes in pediatric ALL patients with and without CNS ...

4. nature.com nature.com/articles/s41598-025-94556-3

Total body irradiation versus chemotherapy myeloablative ... Results of patients with allo-HSCT who also achieved negative MRD after3 chemotherapy cycles according to TBI and non-TBI conditioning regimens.

5. link.springer.com link.springer.com/article/10.1007/s00277-025-06407-w

Comparison of total body irradiation (TBI) and Non- ... Our findings suggest that non-TBI conditioning regimens represent a viable alternative for PTCL patients undergoing allo-HSCT, potentially offering comparable ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12533790/

Outcomes of Allogeneic Hematopoietic Stem Cell ... Haploidentical HSCT improved one-year survival (77.9% vs. 62.0% with chemotherapy) in elderly AML, with lower relapse (16.5% vs. 56.6%). Matched ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265024024467

Review Article Efficacy and Safety of Total Body Irradiation ... Hematopoietic stem cell transplantation (HSCT) is a potentially curative option for adults with acute lymphoblastic leukemia (ALL) who have achieved remission.

8. astctjournal.org astctjournal.org/article/S1083-8791(18)31209-6/fulltext

Efficacy and Safety of Allogeneic Hematopoietic Stem Cell ... The 2-year overall survival (OS) after allo-HSCT was 71.1% and the DFS rate was 70.9%. The 2-year OS and DFS in the CR1 group was better than that of in CR2 ...

9. clinical-lymphoma-myeloma-leukemia.com clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(24)02446-7/abstract

Efficacy and Safety of Total Body Irradiation Versus ... When used for conditioning prior to HSCT, TBI-based conditioning regimens demonstrate superior OS, EFS, and relapse outcomes compared to CHT-based regimens.