Clinical trial NCT04380831: TBI Using IMRT and Cyclophosphamide Prior to Stem Cell Transplant for the Treatment of Severe Systemic Sclerosis
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Systemic Scleroderma
Lead sponsor: City of Hope Medical Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2020-05-08
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Mean lung dose
timeFrame: Up to day 100
measure: Mean kidney dose
timeFrame: Up to day 100
Secondary outcomes:
measure: Dose homogeneity for lungs, kidneys, and total body
timeFrame: Up to day 100
measure: Transplant-related mortality
timeFrame: Day 30 and day 100
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
Study officials:
affiliation: City of Hope Medical Center
name: Jeffrey Y Wong
role: PRINCIPAL_INVESTIGATOR
References: