HSCT for Leukemia and Lymphoma

Recruiting in Palo Alto (17 mi)

Overseen by Punita Grover, MD

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Masonic Cancer Center, University of Minnesota

Disqualifiers: Active CNS malignancy, uncontrolled infection, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This is a Phase II study of allogeneic hematopoietic stem cell transplant (HCT) using a myeloablative preparative regimen (of either total body irradiation (TBI); or, fludarabine/busulfan for patients unable to receive further radiation). followed by a post-transplant graft-versus-host disease (GVHD) prophylaxis regimen of post-transplant cyclophosphamide (PTCy), tacrolimus (Tac), and mycophenolate mofetil (MMF).

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.

What data supports the effectiveness of the treatment HSCT with Non-TBI Regimen for Leukemia and Lymphoma?

Research shows that using total body irradiation (TBI) as part of the conditioning regimen before allogeneic hematopoietic stem cell transplantation (HSCT) can improve overall survival and reduce relapse rates in patients with acute lymphoblastic leukemia (ALL) compared to chemotherapy-only regimens. However, non-TBI regimens can still be effective, especially in pediatric patients with central nervous system involvement, offering similar outcomes to TBI regimens. ^{1 2 3 4 5}

Is allogeneic hematopoietic stem cell transplantation (HSCT) generally safe for humans?

Research shows that allogeneic hematopoietic stem cell transplantation (HSCT) can be generally safe, but it may cause some early side effects like oral sores and stomach issues. Serious complications are rare, but one study noted a case of liver and kidney issues, and another mentioned a risk of severe immune reactions. Overall, it is considered well-tolerated, but more studies are needed to understand long-term safety. ^{1 2 6 7 8}

How does the treatment HSCT with Non-TBI and TBI Regimen differ from other treatments for leukemia and lymphoma?

HSCT (Hematopoietic Stem Cell Transplantation) with TBI (Total Body Irradiation) is unique because it uses radiation to prepare the body for the transplant, which can lead to better survival rates and lower relapse rates compared to chemotherapy alone. This treatment is particularly beneficial for patients with high-risk or relapsed leukemia and lymphoma, offering a potential cure when other treatments have failed. ^{1 2 4 9 10}

Research Team

Punita Grover, MD

Principal Investigator

Masonic Cancer Center, University of Minnesota

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• HSCT with Non-TBI Regimen (Hematopoietic Stem Cell Transplantation)
• HSCT with TBI Regimen (Hematopoietic Stem Cell Transplantation)

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.

Participant Groups

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 Canada, Japan for the following indications:

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+

Dr. Melissa A. Geller

Masonic Cancer Center, University of Minnesota

Chief Medical Officer since 2022

MD from University of Minnesota

Dr. Jeffrey Miller

Masonic Cancer Center, University of Minnesota

Chief Executive Officer

MD from University of Minnesota

Findings from Research

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]

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]

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]

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 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 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]

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]

References

1. England 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. [2021]

2. United States 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. [2021]

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

Effect of conditioning regimen on the outcome of bone marrow transplantation from an unrelated donor. [2019]

4. United States 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. [2023]

5. United States 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. [2018]

6. England 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. [2021]

7. Germany pubmed.ncbi.nlm.nih.gov

Total-body irradiation--role and indications: results from the German Registry for Stem Cell Transplantation (DRST). [2019]

8. Germany 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. [2022]

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

Allogeneic hematopoietic stem cell transplantation for lymphoma. [2019]

10. China pubmed.ncbi.nlm.nih.gov

[Allogeneic Hematopoietic Stem Cell Transplantation for Treatment of T Cell Lymphoblastic Lymphoma - Clinical observation of 10 Cases]. [2018]