108 Participants Needed

Total Marrow and Lymphoid Irradiation and Chemotherapy for Acute Leukemia

Age: < 65
Sex: Any
Trial Phase: Phase 2
Sponsor: City of Hope Medical Center
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

Trial Summary

What is the purpose of this trial?

This phase II trial studies the safety and efficacy of total marrow and lymphoid irradiation (TMLI) in combination with two chemotherapy drugs, etoposide and cyclophosphamide, as a preparative regimen before donor stem cell transplant in treating patients with high-risk acute lymphocytic leukemia (ALL) or acute myeloid leukemia (AML) who have failed previous therapy. Intensity-modulated radiation therapy (IMRT) uses imaging to provide a three-dimensional view of the area to be irradiated. Doctors can then shape and direct the radiation beams at the area from multiple directions while avoiding, as much as possible, nearby organs. TMLI is a method of using IMRT to direct radiation to the bone marrow. Radiation therapy is given before transplant to suppress the immune system, prevent rejection of the transplanted cells, and wipe out any remaining cancer cells. TMLI may allow a greater radiation dose to be delivered to the bone marrow as a preparative regimen before transplant while causing fewer side effects than standard radiation therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it does mention that chemotherapy for controlling white blood cell counts is allowed within 14 days of starting the study.

What data supports the effectiveness of this treatment for acute leukemia?

Research shows that using a combination of high-dose etoposide, cyclophosphamide, and total body irradiation before a bone marrow transplant can improve outcomes for patients with acute leukemia. In children with less advanced disease, this approach resulted in a 68% event-free survival rate over three years, indicating good effectiveness.12345

Is the combination of total body irradiation, etoposide, and cyclophosphamide safe for use in humans?

The combination of total body irradiation, etoposide, and cyclophosphamide has been reported to be generally safe for both adults and children undergoing allogeneic bone marrow transplantation, although there is a risk of severe side effects such as fever, rash, nausea, and in rare cases, severe allergic reactions.24678

How does the treatment of Total Marrow and Lymphoid Irradiation and Chemotherapy for Acute Leukemia differ from other treatments?

This treatment is unique because it combines total marrow irradiation (TMI) with chemotherapy drugs like cyclophosphamide and etoposide, specifically targeting the bone marrow and lymphoid tissues, which may reduce side effects compared to traditional total body irradiation (TBI). It aims to improve outcomes by focusing radiation on areas most affected by leukemia, potentially offering better disease control and fewer complications.49101112

Research Team

AS

Anthony Stein, MD

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for adults with high-risk acute lymphocytic leukemia (ALL) or acute myeloid leukemia (AML) who haven't responded to previous treatments. Participants need a compatible bone marrow donor, good physical function, and normal organ function tests. They must not be pregnant, agree to use contraception, and can't have had certain prior treatments that would conflict with the trial.

Inclusion Criteria

You are able to perform daily activities with a good level of independence and functionality.
Documented (signed) informed consent; the patient, family member and transplant staff physician (physician, nurse, and social worker) meet at least once prior to starting the transplant procedure; during this meeting all pertinent information with respect to risks and benefits to donor and recipient will be presented; alternative treatment modalities will be discussed; the risks are explained in detail in the enclosed consent forms
Agreement of men AND women-of-child-bearing-potential to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
See 12 more

Exclusion Criteria

Prior radiation therapy that would exclude the use of TMLI
Patients with psychological or medical condition that patient's physician deems unacceptable to proceed to allogeneic hematopoietic stem cell transplantation
Women who are planning to become pregnant or breast feed during the trial
See 6 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants undergo image guided total marrow and lymphoid irradiation (TMLI) on days -9 to -5

1 week
5 visits (in-person)

Chemotherapy

Participants receive etoposide IV on day -4 and cyclophosphamide IV on day -2

1 week
2 visits (in-person)

Transplant

Participants undergo allogeneic peripheral blood stem cell or bone marrow transplant on day 0

1 day
1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years
Regular visits as per protocol

Treatment Details

Interventions

  • Allogeneic Bone Marrow Transplantation
  • Allogeneic Hematopoietic Stem Cell Transplantation
  • Cyclophosphamide
  • Etoposide
  • Total Marrow Irradiation
Trial OverviewThe study is testing total marrow and lymphoid irradiation (TMLI) combined with etoposide and cyclophosphamide chemotherapy before receiving a stem cell transplant from a donor. TMLI uses advanced imaging to target radiation at the bone marrow while sparing other organs, aiming to prepare patients better for transplantation.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Treatment (TMLI, chemotherapy)Experimental Treatment5 Interventions
Patients undergo image guided TMLI on days -9 to -5, receive etoposide IV on day -4 and cyclophosphamide IV on day -2, and undergo allogeneic peripheral blood stem cell or bone marrow transplant on day 0.

Cyclophosphamide is already approved in United States, European Union, Canada, Japan for the following indications:

🇺🇸
Approved in United States as Cytoxan for:
  • Breast cancer
  • Ovarian cancer
  • Multiple myeloma
  • Leukemia
  • Lymphoma
  • Rheumatoid arthritis
🇪🇺
Approved in European Union as Endoxan for:
  • Breast cancer
  • Ovarian cancer
  • Multiple myeloma
  • Leukemia
  • Lymphoma
  • Rheumatoid arthritis
🇨🇦
Approved in Canada as Neosar for:
  • Breast cancer
  • Ovarian cancer
  • Multiple myeloma
  • Leukemia
  • Lymphoma
  • Rheumatoid arthritis
🇯🇵
Approved in Japan as Endoxan for:
  • Breast cancer
  • Ovarian cancer
  • Multiple myeloma
  • Leukemia
  • Lymphoma

Find a Clinic Near You

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials
614
Recruited
1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Findings from Research

In a study involving 41 children with high-risk acute leukemia, the combination of total body irradiation (TBI), etoposide (VP-16), and cyclophosphamide (CY) showed a high safety profile, with only one case of fatal regimen-related toxicity reported.
The treatment demonstrated good efficacy, with a 3-year event-free survival rate of 68% for patients with early or intermediate stage disease, while those with advanced disease had a significantly lower survival rate of 17%.
Allogeneic bone marrow transplantation for children with acute leukemia: cytoreduction with fractionated total body irradiation, high-dose etoposide and cyclophosphamide.Duerst, RE., Horan, JT., Liesveld, JL., et al.[2013]
The study established maximum tolerable doses (MTD) for etoposide and cyclophosphamide combined with total body irradiation in 37 patients with advanced hematologic malignancies, finding that the regimen was well tolerated by autologous marrow recipients at 44 mg/kg of VP-16 and 103 mg/kg of CY, and by allogeneic marrow recipients at 36 mg/kg of VP-16 and 67 mg/kg of CY.
Despite achieving complete remission in 31 evaluable patients post-transplant, most experienced disease relapse within a few months, highlighting the need for improved long-term outcomes in this patient population.
Etoposide, cyclophosphamide and fractionated total body irradiation as a preparative regimen for marrow transplantation in patients with advanced hematological malignancies: a phase I study.Petersen, FB., Buckner, CD., Appelbaum, FR., et al.[2016]
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.
Etoposide, cyclophosphamide, total-body irradiation, and allogeneic bone marrow transplantation for hematologic malignancies.Giralt, SA., LeMaistre, CF., Vriesendorp, HM., et al.[2017]

References

High-dose etoposide (VP-16)-containing preparatory regimens in allogeneic and autologous bone marrow transplantation for hematologic malignancies. [2018]
Etoposide in leukemia, lymphoma and bone marrow transplantation. [2019]
Improved prognosis with additional medium-dose VP16 to CY/TBI in allogeneic transplantation for high risk ALL in adults. [2018]
Allogeneic bone marrow transplantation for children with acute leukemia: cytoreduction with fractionated total body irradiation, high-dose etoposide and cyclophosphamide. [2013]
Etoposide, cyclophosphamide and fractionated total body irradiation as a preparative regimen for marrow transplantation in patients with advanced hematological malignancies: a phase I study. [2016]
Efficacy of etoposide, cyclophosphamide, and total body irradiation in allogeneic bone marrow transplantation for adult patients with hematological malignancies. [2014]
[Allergic reactions to teniposide (VM-26) in children with neoplasms]. [2013]
High-dose etoposide in allogeneic stem cell transplantation. [2018]
Etoposide, cyclophosphamide, total-body irradiation, and allogeneic bone marrow transplantation for hematologic malignancies. [2017]
[Bone marrow transplantation with T-cell depletion and hyperfractionated whole-body irradiation. The radiobiological and clinical correlations]. [2008]
11.United Statespubmed.ncbi.nlm.nih.gov
Cyclophosphamide versus etoposide in combination with total body irradiation as conditioning regimen for adult patients with Ph-negative acute lymphoblastic leukemia undergoing allogeneic stem cell transplant: On behalf of the ALWP of the European Society for Blood and Marrow Transplantation. [2019]
Helical tomotherapy targeting total bone marrow after total body irradiation for patients with relapsed acute leukemia undergoing an allogeneic stem cell transplant. [2012]