95 Participants Needed

Non-TBI Conditioning for HCT in Acute Lymphoblastic Leukemia

Recruiting at 23 trial locations
LG
Overseen ByLiz Gourdine
Age: < 65
Sex: Any
Trial Phase: Phase 2
Sponsor: Pediatric Transplantation & Cellular Therapy Consortium
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 2 JurisdictionsThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

This study will evaluate the use of non- TBI (total body irradiation) conditioning for B-ALL patients with low risk of relapse as defined by absence of NGS-MRD (next generation sequencing minimal residual disease) before receiving a hematopoietic cell transplant (HCT). Patients diagnosed with B-ALL who are candidates for HCT will be screened by NGS-MRD on a test of bone marrow done before the HCT. Subjects who are pre-HCT NGS-MRD negative will be eligible to receive a non-TBI conditioning regimen as part of the treatment cohort of the study. Subjects who are pre-HCT NGS-MRD positive will be treated as per treating center standard and will be followed in an observational cohort (HCT center standard of care).

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor to get specific guidance based on your situation.

What data supports the effectiveness of the treatment Myeloablative allogeneic HCT with a non-TBI conditioning regimen for Acute Lymphoblastic Leukemia?

The research does not provide direct evidence for the effectiveness of non-TBI conditioning regimens in Acute Lymphoblastic Leukemia, but it highlights that myeloablative conditioning, in general, is an effective therapy for hematologic malignancies, and nonmyeloablative regimens have been developed to reduce toxicity while relying on the immune system to fight cancer.12345

Is non-TBI conditioning for HCT generally safe in humans?

Non-TBI conditioning regimens for hematopoietic cell transplantation (HCT) have been shown to have lower severe toxicities and nonrelapse mortality compared to traditional myeloablative regimens, making them a safer option for patients, especially those who are older or have other health issues.23678

How is the non-TBI conditioning treatment for acute lymphoblastic leukemia different from other treatments?

The non-TBI conditioning treatment for acute lymphoblastic leukemia is unique because it avoids the use of total body irradiation (TBI), which is commonly used in other conditioning regimens. This approach may reduce some of the toxic side effects associated with TBI, making it a potentially safer option for patients, especially in settings where TBI facilities are not available.39101112

Research Team

AH

Abdel-Azim Hisham, MD

Principal Investigator

Loma Linda University

TQ

Troy Quigg, DO, MS

Principal Investigator

Helen DeVos Children's Hospital

Eligibility Criteria

This trial is for children, adolescents, and young adults aged 1-25 with B-ALL leukemia who are candidates for a stem cell transplant. They must have low relapse risk indicated by negative NGS-MRD (a type of genetic test) in their bone marrow before the transplant. Participants need to be in first or second remission and have good organ function. Those with certain conditions like CNS relapse history or HIV are not eligible.

Inclusion Criteria

My family or doctor decided against a specific treatment even though tests showed I might benefit from it.
I am receiving my first bone marrow transplant for T-ALL or MPAL.
I have ALL and am undergoing a specific bone marrow transplant.
See 8 more

Exclusion Criteria

I haven't had any cancer, except for skin cancer, in the last 5 years.
I have not had a CNS relapse while in my second complete remission.
I received inotuzumab treatment before my stem cell transplant.
See 9 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks
1 visit (in-person)

Treatment

Participants receive a myeloablative non-TBI conditioning regimen with busulfan, fludarabine, and thiotepa prior to hematopoietic cell transplantation

Variable, based on conditioning regimen

Follow-up

Participants are monitored for safety and effectiveness after treatment, with NGS-MRD testing at specified intervals

1 year
Multiple visits for NGS-MRD testing at days 42, 100, 180, 270, and 365 post-HCT

Long-term follow-up

Participants are followed for outcome for up to 5 years to estimate event-free survival

5 years

Treatment Details

Interventions

  • Myeloablative allogeneic HCT with a non-TBI conditioning regimen
  • NGS-MRD
Trial OverviewThe study tests if a non-TBI (no total body irradiation) conditioning regimen before hematopoietic cell transplantation can work for patients with B-ALL who show no minimal residual disease through next-generation sequencing. It compares this approach against standard treatments that include TBI.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Treatment ArmExperimental Treatment2 Interventions
Patients enrolled to the observational arm that are NGS-MRD pre-HCT are considered for the Treatment Arm. Patients will receive a myeloablative non-TBI conditioning regimen prior to the transplant consisting on busulfan, fludarabine and thiotepa. Patients will be followed for outcome for up to 5 years.
Group II: Observational ArmExperimental Treatment1 Intervention
Patients are enrolled to the observational arm to proceed with NGS-MRD testing pre-HCT. If NGS-MRD negative, eligible patients may be considered for the Treatment Arm to receive a myeloablative non-TBI conditioning regimen prior to HCT. If NGS-MRD positive, patients may continue in the observational arm and receive HCT under the direction of their transplant physician and followed on the study for outcome.

Myeloablative allogeneic HCT with a non-TBI conditioning regimen is already approved in United States, European Union for the following indications:

🇺🇸
Approved in United States as Myeloablative allogeneic HCT with non-TBI conditioning for:
  • B-cell acute lymphoblastic leukemia (B-ALL) in NGS-MRD negative patients
🇪🇺
Approved in European Union as Myeloablative allogeneic HCT with non-TBI conditioning for:
  • B-cell acute lymphoblastic leukemia (B-ALL) in NGS-MRD negative patients

Find a Clinic Near You

Who Is Running the Clinical Trial?

Pediatric Transplantation & Cellular Therapy Consortium

Lead Sponsor

Children's Hospital Los Angeles

Lead Sponsor

Trials
257
Recruited
5,075,000+

Findings from Research

Allogeneic hematopoietic cell transplantation using nonmyeloablative or reduced-intensity conditioning regimens has shown promising 2-year survival rates of 48% to 79% for older patients and those with medical comorbidities with acute myeloid leukemia in first complete remission.
Retrospective studies indicate that outcomes for patients receiving nonmyeloablative conditioning are comparable to those receiving traditional myeloablative conditioning, suggesting a potential shift in treatment approaches for this patient population.
Hematopoietic cell transplantation after reduced-intensity conditioning for older adults with acute myeloid leukemia in complete remission.Baron, F., Storb, R.[2016]
Nonmyeloablative conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT) provide a safer alternative for older or medically unfit patients with hematologic malignancies, allowing them access to potentially curative treatment that was previously too risky due to high toxicity.
These regimens utilize donor T-cells to target and eliminate malignant cells without the need for intensive chemotherapy or radiotherapy, demonstrating a promising graft-versus-tumor effect and improving the eligibility of patients for HSCT.
Review of "minitransplantation": nonmyeloablative allogeneic hematopoietic stem cell transplantation.Georges, GE., Storb, R.[2019]
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.
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]

References

Hematopoietic cell transplantation after reduced-intensity conditioning for older adults with acute myeloid leukemia in complete remission. [2016]
Review of "minitransplantation": nonmyeloablative allogeneic hematopoietic stem cell transplantation. [2019]
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]
Reduced intensity conditioning for allogeneic hematopoietic cell transplantation: current perspectives. [2018]
Standard versus alternative myeloablative conditioning regimens in allogeneic hematopoietic stem cell transplantation for high-risk acute leukemia. [2019]
Reduced-toxicity conditioning regimen with busulfan, fludarabine, rATG, and 400 cGy TBI in pediatric patients undergoing hematopoietic stem cell transplant for high-risk hematologic malignancies. [2022]
ESTRO ACROP and SIOPE recommendations for myeloablative Total Body Irradiation in children. [2022]
Morbidity and mortality with nonmyeloablative compared with myeloablative conditioning before hematopoietic cell transplantation from HLA-matched related donors. [2021]
Radiation-Free myeloablative allogeneic hematopoietic stem cell transplantation for adult acute lymphoblastic leukemia: A comparison of outcomes between patients with and without central nervous system involvement. [2022]
10.United Statespubmed.ncbi.nlm.nih.gov
Fludarabine, cytarabine, granulocyte colony-stimulating factor and melphalan (FALG with L-PAM) as a reduced toxicity conditioning regimen in children with acute leukemia. [2014]
11.United Statespubmed.ncbi.nlm.nih.gov
Inferior outcomes with reduced intensity conditioning followed by allogeneic hematopoietic cell transplantation in fit individuals with acute lymphoblastic leukemia: a Canadian single-center study and a comparison to registry data. [2021]
12.United Statespubmed.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]