Total Marrow Irradiation With Volumetric Arc Therapy for Patients Unfit for a 12 Gy TBI

Pilot Study of Dose Escalated Total Marrow Irradiation With Volumetric Arc Therapy for Patients With Hematological Malignancies Unfit for a Standard 12 Gy TBI Conditioning Regimen.

Total body irradiation (TBI) is a standard part of the conditioning regimen for bone marrow transplantation (BMT). Several randomized trials have shown superior outcomes using TBI compared with non TBI-containing regimens. Standard TBI is usually delivered over three days for a total dose of 12 Gy with two daily fractions. However, as demonstrated by our group, increasing the TBI dose above 10 Gy is not necessarily associated with better outcome in patients undergoing allogenic BMT for hematologic malignancies. For this reason, patients older than 40 or grafted after relapse are treated at our center with a reduced-dose 10 Gy TBI regimen. This pilot study wishes to investigate in 10 patients with hematological malignancies unfit for a standard 12 Gy TBI conditioning regimen a more targeted, conformal form of treatment, referred as total marrow (TMI), using volumetric Arc Therapy (VMAT). Our hypothesis is that using this technique that can allow deliver a higher total dose to the target while at the same time assuring to the organs at risk (OAR) the same dose normally delivered with a 10 Gy TBI we will improve the therapeutic ratio in these patients.

Study Overview

• Status: Recruiting
• Conditions: Haematological Malignancy
• Intervention / Treatment: Radiation: Volumetric Arc Therapy (VMAT)

Detailed Description

This is a feasibility prospective pilot study. Ten patients ≥ 40 years with hematologic malignancies prior to Bone Marrow Transplant (BMT) will receive a dose escalated hypofractionated Total Marrow Irradiation (TMI) (12 Gy in 3 fractions, daily, on 3 consecutive days).

The current project is a joint initiative in translational and clinical medical research between the Radiation-oncology workgroup and the Bone Marrow transplant workgroup of University Hospitals of Geneva (HUG).

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Thomas Zilli, MD; Phone Number: + 41 79 55 32 563; Email: thomas.zilli@hcuge.ch

Study Locations

• Switzerland
  • Genève, Switzerland, 1205
    • Recruiting
    • University Hospital of Geneva

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Karnofsky performance status ≥ 70
• Presence of any kind of haematological malignancy in complete remission (CR1, CR2 ore CR3) at time of transplantation, with the exception of patients with myelodysplastic syndrome.
• Patients that are scheduled for a BMT either using stem cell derived from bone marrow or peripheral blood stem cells.
• Candidates to receive a 10 Gy TBI treatment.
• Ability to stay still and lying on the treatment couch for at least 45 minutes.
• Informed Consent as documented by signature.

Exclusion Criteria:

• Karnofsky performance status <70 intended as a patient unable to work; able to live at home and care for most personal needs with varying amount of assistance needed.
• Concurrent treatment with other experimental drugs or other anti-cancer therapy.
• Participation in another clinical trial and any concurrent treatment with any investigational drug within 4 weeks prior to trial entry/randomisation.
• Inability to comply with study and follow-up procedures.

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Grade II and III toxicity	(Seattle Regimen-related toxicity grade) 30 days after transplant in patients with hematologic malignancies treated with a dose-escalated hypofractionated VMAT-based TMI	30 days after radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative incidence of Transplant Related Mortality(TRM)	Defined as death occurring from causes that are different other than disease relapse post-transplant	100 days post-bone marrow transplantation
Cumulative incidence of Grade II Organ toxicity	Seattle Regimen-related toxicity grade	up to day 100 post-bone marrow transplantation

Collaborators and Investigators

• Sponsor: Thomas Zilli
• Collaborators: University Hospital, Geneva

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2017
• Primary Completion (Anticipated): April 1, 2021
• Study Completion (Anticipated): April 1, 2025

Study Registration Dates

• First Submitted: August 23, 2017
• First Submitted That Met QC Criteria: August 23, 2017
• First Posted (Actual): August 25, 2017

Study Record Updates

• Last Update Posted (Actual): May 14, 2020
• Last Update Submitted That Met QC Criteria: May 13, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Haematological malignancy; Total Marrow Irradiation; Volumetric Arc Therapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Hematologic Diseases; Neoplasms; Hematologic Neoplasms
• Other Study ID Numbers: 2017-00066

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: No plan

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No