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

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

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

Study Overview

• Status: Completed
• Conditions: Hematologic Malignancy
• Intervention / Treatment: Radiation: Linac Based VMAT TBI

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18

2. 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.

3. Referral from the blood and marrow transplant (BMT) program for full-dose TBI, who meet inclusion and exclusion criterial per BMT SOPs.

   1. BMT program will initiate referral, utilizing Form: 170102, Radiation Oncology Consultation.
   2. 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:

1. Patient receiving less than 1200 cGy of TBI
2. Previous history of thoracic radiation therapy including previous TBI
3. All premenopausal women will require a urine qualitative pregnancy test to exclude pregnancy. Pregnant women will be excluded from the study.
4. Prisoners
5. Patient not meeting transplant criteria per BMT physician.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Patients with Hematologic Malgnancies

Radiation: Linac Based VMAT TBI; 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).

What is the study measuring?

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
Event Free Survival (EFS)	Interval from day of transplant to date of first objective disease progression or relapse or death from any cause. Subjects without these failures will be censored at the last date that they were assessed and deemed failure free.	Up to 1 year post-transplant
Proportion of Patients Who Have Achieved a Maximum Dose to 2cc of the Entire Body (D2cc) < 130% of Rx Dose.	Number of participants with Maximum dose to 2cc of the entire body (D2cc) <130% of Rx dose	Up to 150 days post-transplant
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
Proportion of Patients Who Have Achieved a Maximum Dose to 0.03cc of OARs < 120% of Rx Dose.	Number of participants with Maximum dose to 0.03cc of organs at risk <120% of Rx dose	Up to 150 days post-transplant
Occurrence of Acute GVHD, Transplant Related Mortality, or Mortality in the First 100 Days Following Transplant	Number of participants who experienced acute GVHD or all-cause mortality within 100 days following bone marrow transplant	100 days post-transplant
Proportion of Patients Who Achieved a Mean Dose to Each Kidney (Dmean) < 11Gy	Number of participants with mean dose of <11Gy (1100 cGy) to either kidney	Up to 150 days post-transplant

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Investigators: Principal Investigator: Naamit Gerber, MD, NYU Langone Health

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2020
• Primary Completion (Actual): February 11, 2025
• Study Completion (Actual): February 11, 2025

Study Registration Dates

• First Submitted: August 10, 2020
• First Submitted That Met QC Criteria: August 10, 2020
• First Posted (Actual): August 12, 2020

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Total Body Irradiation; Myeloablative Treatment
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Hematologic Neoplasms
• Other Study ID Numbers: 19-00664

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices) will be shared upon reasonable request.
• IPD Sharing Time Frame: Data will become available beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• IPD Sharing Access Criteria: The investigator who proposed to use the data will have access to the data upon reasonable request. Requests should be directed to naamit.gerber@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes