Stem Cell Transplant for Blood Cancers

Overseen By Usama Gergis, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University

Must not be taking: Alemtuzumab, ATG

Disqualifiers: HIV, CNS malignancy, 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

Compensation: Varies

Number of Visits: Unknown

63 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies the how well donor stem cell transplant works in treating patients with high risk hematologic malignancies. Giving total-body irradiation and chemotherapy before a donor stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. The donated stem cells may also replace the patient's immune cells and help destroy any remaining cancer cells.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since the trial involves chemotherapy and total-body irradiation, it's possible that some medications might need to be adjusted. Please consult with the trial coordinators for specific guidance.

What data supports the effectiveness of the treatment Allogeneic Hematopoietic Stem Cell Transplantation for blood cancers?

Research shows that using total body irradiation (TBI) combined with cyclophosphamide (a chemotherapy drug) as part of the pre-transplant preparation can improve survival outcomes in patients with acute lymphoblastic leukemia (ALL), a type of blood cancer. This combination is a common and effective approach in preparing patients for stem cell transplants. ^{1 2 3 4 5}

Is stem cell transplant for blood cancers generally safe for humans?

Stem cell transplants, including those using donor cells, have been studied for safety. While they can be effective, they come with risks like graft-versus-host disease (GVHD), where the donor cells attack the recipient's body. However, using medications like cyclophosphamide and tacrolimus can help reduce these risks, and recent studies show improved safety outcomes with these treatments. ^{2 6 7 8 9}

How is the treatment of allogeneic hematopoietic stem cell transplantation with cyclophosphamide and total-body irradiation unique for blood cancers?

This treatment is unique because it combines donor stem cell transplantation with a conditioning regimen of cyclophosphamide (a chemotherapy drug) and total-body irradiation (TBI), which helps prepare the body to accept new stem cells by suppressing the immune system and eliminating cancer cells. The use of TBI and cyclophosphamide is a well-established approach for treating acute and chronic leukemias, and it aims to reduce the risk of graft-versus-host disease (a condition where the donor cells attack the recipient's body) while enhancing the effectiveness of the transplant. ^{1 3 10 11 12}

Research Team

Usama Gergis, MD

Principal Investigator

Sidney Kimmel Cancer Center at Thomas Jefferson University

Eligibility Criteria

This trial is for adults with high-risk blood cancers who have a partially matched related donor. They must be in good health with proper heart, lung, liver function, and kidney clearance. A performance status showing they're mostly independent in daily activities is required. HIV-positive individuals, those with central nervous system cancer involvement or significant psychiatric disorders are excluded.

Inclusion Criteria

I have a rare condition that could benefit from a stem cell transplant.

Patients must be willing to use contraception if they have childbearing potential

My heart, lungs, liver, kidneys, and overall health are in good condition.

Exclusion Criteria

I am HIV positive.

I cannot tolerate certain doses of cyclophosphamide or total body irradiation.

> 5 Comorbidity Points on the Hematopoietic Cell Transplant Co-Morbidity Index (HCT CI)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants undergo Total-Body Irradiation (TBI) twice daily on days -10 to -8

1 week

Daily visits for radiation

Chemotherapy and Transplantation

Participants receive chemotherapy and undergo Allogeneic Hematopoietic Stem Cell Transplantation

4 weeks

Inpatient stay for chemotherapy and transplantation

Follow-up

Participants are monitored for safety, effectiveness, and immune recovery after treatment

2 years

Treatment Details

Interventions

• Allogeneic Hematopoietic Stem Cell Transplantation
• Cyclophosphamide
• Donor Lymphocyte Infusion
• Mycophenolate Mofetil
• Tacrolimus
• Total-Body Irradiation

Trial Overview The study tests if a stem cell transplant from a donor after receiving full-body radiation and chemotherapy can treat patients with aggressive blood cancers effectively without causing severe side effects. The goal is to stop cancer growth and prevent the immune system from rejecting the new cells.

Participant Groups

Group I: Treatment (TBI, DLI, chemotherapy, HSCT) Experimental Treatment 6 Interventions

Patients undergo Total-Body Irradiation (TBI) twice daily on days -10 to -8 and and donor lymphocyte infusion (DLI) on day -6. Patients receive cyclophosphamide IV on days -3 and -2, tacrolimus IV beginning on day -1 and then orally at least 2 or 3 days prior to discharge with taper starting on day 42, and mycophenolate mofetil IV twice daily on days -1 to 28. Patients undergo Allogeneic Hematopoietic Stem Cell Transplantation on day 0.

Allogeneic Hematopoietic Stem Cell Transplantation is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Allogeneic Hematopoietic Stem Cell Transplantation for:

• Primary immunodeficiency disorders
• Immune dysregulatory disorders
• Hemophagocytic lymphohistiocytosis
• Bone marrow failure syndromes
• Hemoglobinopathies

Approved in United States as Allogeneic Hematopoietic Stem Cell Transplantation for:

• Primary immunodeficiency disorders
• Immune dysregulatory disorders
• Hemophagocytic lymphohistiocytosis
• Bone marrow failure syndromes
• Hemoglobinopathies

Approved in Canada as Allogeneic Hematopoietic Stem Cell Transplantation for:

• Primary immunodeficiency disorders
• Immune dysregulatory disorders
• Hemophagocytic lymphohistiocytosis
• Bone marrow failure syndromes
• Hemoglobinopathies

Approved in Japan as Allogeneic Hematopoietic Stem Cell Transplantation for:

• Primary immunodeficiency disorders
• Immune dysregulatory disorders
• Hemophagocytic lymphohistiocytosis
• Bone marrow failure syndromes
• Hemoglobinopathies

Who Is Running the Clinical Trial?

Sidney Kimmel Cancer Center at Thomas Jefferson University

Lead Sponsor

Trials

164

Recruited

10,900+

Findings from Research

In a study of 75 adult patients undergoing hematopoietic stem cell transplantation (HSCT) with myeloablative conditioning, the timing of total body irradiation (TBI) before HSCT did not significantly affect overall survival or progression-free survival rates.

Regardless of the interval between TBI and HSCT (ranging from 2 to 10 days), there were no significant differences in relapse rates, non-relapse mortality, or the incidence of acute and chronic graft-versus-host disease, suggesting that the timing of TBI may not be critical for patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of the duration between total body irradiation and stem cell infusion on the outcome of allogeneic transplantation with myeloablative conditioning. Akahoshi, Y., Kako, S., Nakano, H., et al.[2015]

In a meta-analysis of 15 randomized controlled trials involving 10,160 pediatric patients, total body irradiation plus cyclophosphamide (TBI/CY) was found to be more effective than busulfan plus cyclophosphamide (BU/CY) in reducing transplant failure rates and improving long-term disease-free survival rates.

The TBI/CY regimen also demonstrated a lower incidence of adverse reactions compared to the BU/CY regimen, indicating it may be a safer option for pediatric hematopoietic stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two Different Transplant Preconditioning Regimens Combined with Irradiation and Chemotherapy in the Treatment of Childhood Leukemia: Systematic Review and Meta-Analysis. Wang, X., Mu, D., Geng, A., et al.[2023]

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]

Children with acute lymphoblastic leukemia (ALL) who underwent total body irradiation (TBI)-based conditioning before allogeneic hematopoietic cell transplantation (allo-HCT) had significantly better long-term outcomes compared to those conditioned with chemotherapy, with a 2-year overall survival rate of 84% versus 60.5%.

TBI conditioning, especially when combined with transplantation during the first remission of ALL, was associated with improved overall survival, event-free survival, and graft-versus-host-disease-free-relapse-free survival, highlighting its efficacy in enhancing transplant success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute Lymphoblastic Leukemia in Children: Better Transplant Outcomes After Total Body Irradiation-based Conditioning. Styczynski, J., Debski, R., Czyzewski, K., et al.[2021]

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]

Total body irradiation (TBI) in haploidentical hematopoietic stem cell transplantation (HSCT) shows comparable survival outcomes and rates of relapse and graft-versus-host disease (GVHD) to traditional methods, despite the challenges of using haploidentical donors.

Recent advancements in TBI techniques, such as dose restriction and organ shielding, along with the use of post-transplantation cyclophosphamide and rituximab, have improved safety and efficacy, particularly for patients with B-cell lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Use of Total Body Irradiation in Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation. Jung, J., Lee, H., Suh, YG., et al.[2021]

In a study of 35 patients undergoing allogeneic peripheral blood stem cell transplantation (alloPBSCT), a combination of post-transplant cyclophosphamide and standard immunosuppressants effectively reduced the incidence of acute and chronic graft-versus-host disease (GVHD) to 17% and 7%, respectively, with no severe grade IV GVHD cases reported.

The approach resulted in an impressive 2-year nonrelapse mortality rate of just 3% and maintained overall survival at 77%, demonstrating that this strategy not only controls GVHD but also preserves the beneficial graft-versus-tumor effect essential for combating hematologic malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-Transplant Cyclophosphamide and Tacrolimus-Mycophenolate Mofetil Combination Prevents Graft-versus-Host Disease in Allogeneic Peripheral Blood Hematopoietic Cell Transplantation from HLA-Matched Donors. Carnevale-Schianca, F., Caravelli, D., Gallo, S., et al.[2018]

Allogeneic hematopoietic stem cell transplantation (alloSCT) can potentially cure many blood and immune diseases, but it faces challenges like toxicity and the difficulty of finding compatible donors.

Recent advancements using high-dose post-transplantation cyclophosphamide (PT/Cy) allow for successful transplants from partially HLA-mismatched donors, reducing the risks of graft rejection and severe complications like graft-versus-host disease (GVHD).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-transplantation cyclophosphamide for tolerance induction in HLA-haploidentical bone marrow transplantation. Luznik, L., O'Donnell, PV., Fuchs, EJ.[2021]

A new nonmyeloablative approach to allogeneic hematopoietic stem cell transplantation (alloHCT) allows for mixed hematopoietic chimerism, which can lead to less toxicity and lower rates of severe acute graft versus host disease (GVHD).

Clinical trials have shown that this method reduces transplant-related mortality (TRM) and ongoing research aims to replace traditional pretransplant chemotherapy and radiation with safer anti-T-cell agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nonmyeloablative allogeneic hematopoietic stem cell transplantation: minitransplantation]. Machaczka, M., Rucińska, M., Skotnicki, AB.[2006]

In a study of 79 patients undergoing allogeneic bone marrow transplantation, the combination of etoposide, cyclophosphamide, and fractionated total-body irradiation (TBI) showed a 57% overall survival rate at 3 years for patients with early leukemia, indicating its efficacy as a preparative regimen.

Patients with advanced disease experienced significantly lower survival rates (17%) and higher toxicity, highlighting that this regimen is more effective and safer for those with early-stage hematologic malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etoposide, cyclophosphamide, total-body irradiation, and allogeneic bone marrow transplantation for hematologic malignancies. Giralt, SA., LeMaistre, CF., Vriesendorp, HM., et al.[2017]

The study involved 54 patients with acute leukemia and 34 with chronic myeloid leukemia, showing that a conditioning regimen of hyperfractionated total body irradiation (TBI), cyclophosphamide, and thiothepa resulted in a disease-free survival (DFS) of 55.5% for acute leukemia patients at a median follow-up of 40 months.

The addition of thiothepa significantly improved DFS in chronic myeloid leukemia patients, with a 66.6% DFS at a median follow-up of 12 months, while the group without thiothepa had only a 10% DFS at a median follow-up of 60 months, indicating the regimen's efficacy and tolerability despite some patients developing interstitial pneumonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Bone marrow transplantation with T-cell depletion and hyperfractionated whole-body irradiation. The radiobiological and clinical correlations]. Latini, P.[2008]

In a study of 77 patients undergoing haploidentical stem cell transplantation for hematologic malignancies, the conditioning regimen with busulfan plus cyclophosphamide (BU+CY) resulted in a significantly better 3-year overall survival rate of 56.4% compared to 31.6% for total body irradiation plus cyclophosphamide (TBI+CY).

The BU+CY regimen also demonstrated a lower short-term relapse rate (2.56% at 1 year) compared to TBI+CY (26.67%), while both regimens had similar rates of acute graft-versus-host disease (GVHD), but TBI+CY was associated with a higher incidence of chronic GVHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of BU and CY versus TBI and CY as conditioning regimens on the efficacy of haploidentical stem cell transplantation in patients with hematologic malignancy]. Shao, Q., Han, D., Liu, D., et al.[2014]

References

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

Effect of the duration between total body irradiation and stem cell infusion on the outcome of allogeneic transplantation with myeloablative conditioning. [2015]

2. England pubmed.ncbi.nlm.nih.gov

Two Different Transplant Preconditioning Regimens Combined with Irradiation and Chemotherapy in the Treatment of Childhood Leukemia: Systematic Review and Meta-Analysis. [2023]

3. 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]

4. Greece pubmed.ncbi.nlm.nih.gov

Acute Lymphoblastic Leukemia in Children: Better Transplant Outcomes After Total Body Irradiation-based Conditioning. [2021]

5. 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]

6. Korea (South) pubmed.ncbi.nlm.nih.gov

Current Use of Total Body Irradiation in Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation. [2021]

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

Post-Transplant Cyclophosphamide and Tacrolimus-Mycophenolate Mofetil Combination Prevents Graft-versus-Host Disease in Allogeneic Peripheral Blood Hematopoietic Cell Transplantation from HLA-Matched Donors. [2018]

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

Post-transplantation cyclophosphamide for tolerance induction in HLA-haploidentical bone marrow transplantation. [2021]

9. Poland pubmed.ncbi.nlm.nih.gov

[Nonmyeloablative allogeneic hematopoietic stem cell transplantation: minitransplantation]. [2006]

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

Etoposide, cyclophosphamide, total-body irradiation, and allogeneic bone marrow transplantation for hematologic malignancies. [2017]

11. Italy pubmed.ncbi.nlm.nih.gov

[Bone marrow transplantation with T-cell depletion and hyperfractionated whole-body irradiation. The radiobiological and clinical correlations]. [2008]

12. China pubmed.ncbi.nlm.nih.gov

[Effect of BU and CY versus TBI and CY as conditioning regimens on the efficacy of haploidentical stem cell transplantation in patients with hematologic malignancy]. [2014]