TBI Using IMRT and Cyclophosphamide Prior to Stem Cell Transplant for the Treatment of Severe Systemic Sclerosis

Systemic Scleroderma Clinical Trial

Official title:

Pilot Study of Total Body Irradiation Using Intensity Modulated Radiation Therapy (IMRT) and Cyclophosphamide Conditioning Regimen Prior to Autologous Hematopoietic Cell Transplantation in Patients With Severe Systemic Sclerosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04380831
• Other study ID #: 20006
• Secondary ID: NCI-2020-0274420
• Status: Recruiting
• Phase: Early Phase 1
• Start date: February 24, 2022
• Est. completion date: December 22, 2024

Study information

• Verified date: March 2024
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This early phase I trial studies the side effects and feasibility of total body irradiation using intensity modulation radiation therapy (IMRT) when given in combination with cyclophosphamide prior to stem cell transplant to treat severe systemic sclerosis. IMRT delivers total body radiation therapy more precisely and may reduce radiation exposure to sensitive normal organs. Giving chemotherapy, such as cyclophosphamide, and total body irradiation before a donor stem cell transplant helps kill cancer cells in the body and helps make room in the bone marrow for new blood-forming cells (stem cells) to grow. Giving IMRT and cyclophosphamide prior to stem cell transplant may work better in treating severe systemic sclerosis and reduce radiation doses to lung and kidneys compared to cyclophosphamide alone.

Description:

PRIMARY OBJECTIVES: I. To assess the feasibility of using IMRT to deliver total body irradiation (TBI) to 800 cGy while keeping mean lung and kidney doses to 200 cGy. II. To assess the safety/feasibility of total body irradiation using IMRT (IMRT TBI) in systemic sclerosis patients undergoing autologous hematopoietic stem cell transplantation. SECONDARY OBJECTIVES: I. To evaluate dose homogeneity and dose sparing to lung and kidneys. II. To evaluate transplant-related mortality at 30 days and 100 days post IMRT TBI. OUTLINE: Patients undergo TBI using IMRT twice daily (BID) on days -5 and -4 in the absence of disease progression or disease progression. Patients then receive cyclophosphamide on days -3 and -2 and undergo HSCT on day 0 in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up on days 30 and 100.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: December 22, 2024
• Est. primary completion date: December 22, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Karnofsky performance status (KPS) >= 70
• Systemic sclerosis patients evaluated within 30 days of start of conditioning regimen who would be candidates for TBI-cyclophosphamide (Cy) per City of Hope (COH) guidelines and standard operating procedures (SOP) for autologous hematopoietic cell transplant
• Patients must be suitable for TBI conditioning regimens as part of transplant per radiation the referring hematologist
• Patients must have adequate organ function for HCT as determined by the hematologist
• Women of child-bearing potential and men must agree 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
• All subjects must have the ability to understand the treatment and the willingness to sign a written informed consent

Exclusion Criteria:

• Patients should not have any uncontrolled illness including ongoing or active infection
• Prior history of radiation therapy must be presented to study principal investigator (PI) for eligibility determination
• Pregnant women are excluded from this study because total body irradiation is an agent with the potential for teratogenic or abortifacient effects
• Subjects, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study

Related Conditions & MeSH terms

• Scleroderma, Diffuse
• Scleroderma, Systemic
• Systemic Scleroderma

Intervention

Procedure:
• Allogeneic Hematopoietic Stem Cell Transplantation
Undergo HSCT

Drug:
• Cyclophosphamide
Undergo HSCT

Radiation:
• Intensity-Modulated Radiation Therapy
Undergo TBI using IMRT

Procedure:
• Total-Body Irradiation
Undergo TBI using IMRT

Locations

Country	Name	City	State
United States	City of Hope Medical Center	Duarte	California

Sponsors (2)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean lung dose	The study will be deemed feasible if >= 80% of patients complete the intensity modulation radiation therapy (IMRT) to the total dose of 800 cGy, mean lung and kidney doses are limited to 200 cGy or less.	Up to day 100
Primary	Mean kidney dose	The study will be deemed feasible if >= 80% of patients complete the IMRT to the total dose of 800 cGy, mean lung and kidney doses are limited to 200 cGy or less.	Up to day 100
Secondary	Dose homogeneity for lungs, kidneys, and total body	"Dose homogeneity for lung, kidney and total body will use the DVH (dose volume histograms) generated by the treatment plan for each of these regions. The goal is to keep the lung and kidney dose homogeneity to with +/- 15% of the mean dose to that organ. The goal is to keep total body dose homogeneity to within +/- 15% of the prescribed total body dose of 8 Gy."	Up to day 100
Secondary	Transplant-related mortality	Measured by comparing the transplant-related mortality rates on day 30 compared to day 100.	Day 30 and day 100