A Phase II Single-arm Study of Total Body Irradiation With Linac Based VMAT and IGRT

Study Overview
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Brief Summary
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Single institution study of safety of linac based VMAT TBI for myeloablative treatment in hematologic malignancies.

Detailed Description
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Total Body Irradiation (TBI) continues to play an important role in myeloablative and non-myeloablative conditioning regimens for Allogeneic Stem Cell Transplant (ASCT). When TBI is used as part of a myeloablative regimen, it is combined with chemotherapy to eradicate malignant cells, as well as to immunosuppress the host to prevent rejection of donor hematopoietic progenitor cells (HPC). This study is a single-institution study to assess the safety of linac based VMAT TBI for myeablative sreatment in hematologic malignancies.

Official Title
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A Phase II Single-Arm Study of Total Body Irradiation With Linac Based Volumetric Modulated Arc Therapy (VMAT) and Image Guided Radiation Therapy (IGRT)

Conditions
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Hematologic Malignancy

Intervention / Treatment
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* Radiation: Linac Based VMAT TBI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 Patients undergoing related, unrelated (including cord blood) hematopoietic progenitor cell (HPC) transplant, in which the protocol requires >12 Gray of TBI, as part of the conditioning regimen. a. Conditioning regimens outlined per BMT SOP: CLNTX007: Selection of Conditioning Regimens for Blood and Marrow Transplantation - ADULTS. Referral from the blood and marrow transplant (BMT) program for full-dose TBI, who meet inclusion and exclusion criterial per BMT SOPs. BMT program will initiate referral, utilizing Form: 170102, Radiation Oncology Consultation. Patients undergo pre-transplant testing, as defined in BMT SOPs:CLNAL002: Related (MRD, Haplo) Allogeneic Recipient Evaluation and Management or CLNAL011: Unrelated (MUD, MMUD, CBU) Allogeneic Recipient Evaluation and Management, per below. i. BMT SOP's include baseline pulmonary function tests (PFTs). Patient with decreased FVC, FEV1 and or DLCO (adjusted for hemoglobin) or pulmonary history will have pulmonary consult, at the discretion of the BMT physician prior to undergoing myeloablative radiation. ii. Medical history and physical by BMT provider. iii. The following laboratory tests (additional testing may be required for positive results): ABO group and Rh type Red Blood Cell Antibody Screen. HLA typing and confirmatory typing HLA antibody screen, class I and II, performed within 30 days of transplant. Complete blood count (CBC) with differential. Basic metabolic panel, including glucose and to include at a minimum electrolyte evaluation of potassium, calcium, magnesium, and phosphorus. Blood urea nitrogen (BUN) Creatinine Liver Function Tests including: Total bilirubin, Alkaline phosphatase, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Lactate dehydrogenase (LDH), Albumin, Total Protein, Urinalysis Exclusion Criteria: Patient receiving less than 1200 cGy of TBI Previous history of thoracic radiation therapy including previous TBI All premenopausal women will require a urine qualitative pregnancy test to exclude pregnancy. Pregnant women will be excluded from the study. Prisoners Patient not meeting transplant criteria per BMT physician.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients with Hematologic Malgnancies<br> | Radiation: Linac Based VMAT TBI<br>* Use of linac based Volumetric Arc Therapy (VMAT) to deliver Total Body Irradiation (TBI). The study intervention is a VMAT based delivery technique using a 6 MV photon beam from a Varian TrueBeam® (Palo Alto, CA) equipped with a Millennium multi-leaf collimation (MLC) system3. TBI will be delivered using a Varian TrueBeam linear accelerator with photon beam VMAT capability. VMAT is a radiation technique combining dynamic photon fluence modulation using multi-leaf collimation (MLC) with gantry rotation to deliver a highly conformal dose distribution with improved target coverage and sparing of organs at risk (OARs).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who achieve excellent coverage while sparing the lung | Excellent coverage while sparing the lung is quantified by meeting the following dosimetric parameters (all parameters must be met): V100%= >90% (90% of PTV volume getting 100% of the dose). D98>85% (98% of the volume getting at least 85% of the dose). Mean Lung dose <900cGy. | Up to 1 year post-transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative incidence rate of idiopathic pneumonia syndrome | Non-infectious pneumonia syndrome is defined by the American Thoracic Society as at least 1 of the following without concurrent infection detected on blood culture, broncoalveolar lavage, lung biopsy or sputum: There must also be the absence of cardiac dysfunction, acute renal failure, or iatrogenic fluid overload as etiology for pulmonary dysfunctionMultilobar infiltrates on chest radiograph or computed tomography (CT); Symptoms and signs of pneumonia including dyspnea, cough, cyanosis, hypoxia or pyrexia; New or increased restrictive patters on pulmonary function testing or increased alveolar to arterial oxygen difference | Up to 100 days post-transplant | 
| Occurrence of acute GVHD, transplant related mortality, or mortality in the first 100 days following transplant |  | 100 days post-transplant | 
| Event Free Survival (EFS) |  | Up to 1 year post-transplant | 
| Proportion of patients who achieved a mean dose to each kidney (Dmean) < 11Gy |  | Up to 150 days post-transplant | 
| Proportion of patients who have achieved a maximum dose to 2cc of the entire body (D2cc) < 130% of Rx dose. |  | Up to 150 days post-transplant | 
| Proportion of patients who have achieved a maximum dose to 0.03cc of OARs < 120% of Rx dose. |  | Up to 150 days post-transplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myeloablative Treatment, Total Body Irradiation