Automated Total Marrow and Lymphoid Irradiation for Allogeneic Hematopoietic Cell Transplant

Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-70
SponsorStanford University

About this trial

Intensive conditioning regimens used in allogeneic hematopoietic cell transplant (HCT) help to eliminate hematologic tumors and reduce the risk of relapse, but are also characterized by high toxicity. Total marrow and lymphoid irradiation (TMLI) is a specialized radiation technique that specifically targets marrow and lymphoid tissue to maximize antitumor efficacy while reducing off target toxicity. Despite these benefits, TMLI is technically challenging and time consuming. The radiation oncology team at Stanford has developed an automated TMLI platform to overcome these challenges. In this phase II trial, automation will be incorporated into a previously validated conditioning regimen of fludarabine/cyclophosphamide/TMLI HCT with post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis to confirm the feasibility and safety of automation in patients receiving allogeneic HCT for high-risk myeloid malignancies.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age 18 to 60 years (inclusive)

HCT Co-Morbidity score (HCT-CI) < 5 (http://www.qxmd.com/calculate-online/hematology/hct-ci)(31)

Adequate performance status is defined as Karnofsky score ≥ 70%

Patients must be receiving an allogeneic peripheral blood stem cell graft

Disqualifiers

Pregnant or breast feeding. The agents used in this study include Pregnancy Category D: known to cause harm to a fetus. Females of childbearing potential must have a negative pregnancy test prior to starting therapy.

Untreated active infection. Controlled or asymptomatic infections requiring continued antimicrobial therapy are permissible.

Active HIV infection, defined as HIV infection with detectable viral load

Active central nervous system malignancy

Trial design

Design model

Single group

Treatments tested in this trial

  • VMAT-Based Total Marrow and Lymphoid Irradiation (TMLI)

    Radiation

    Patients receive VMAT-based TMLI with daily image-guided radiation therapy (IGRT) for treatment localization and verification prior to radiation delivery.

  • Fludarabine

    Drug

    Fludarabine 25 mg/m² IV administered daily on Days -7 through -3.

  • Cyclophosphamide

    Drug

    Cyclophosphamide 14.5 mg/kg IV on Days -7 and -6 as part of conditioning and 50 mg/kg IV on Days +3 and +4 as post-transplant GVHD prophylaxis.

  • Allogeneic Peripheral Blood Stem Cell Transplantation (PBSCT)

    Biological/Vaccine

    Allogeneic peripheral blood stem cell transplantation administered on Day 0.

  • Mycophenolate mofetil (MMF)

    Drug

    Mycophenolate mofetil initiated on Day +5 and continued through Day +35 for GVHD prophylaxis.

  • Tacrolimus

    Drug

    Mycophenolate mofetil initiated on Day +5 and continued through Day +35 for GVHD prophylaxis.

Treatment groups

30 Participants
are divided into 2 treatment groups
Group A: Cohort A: Total Marrow and Lymphoid Irradiation (TMLI) 200 cGy BID Conditioning RegimenExperimental treatment 6 interventions
Group B: Cohort B: Total Marrow and Lymphoid Irradiation 150 cGy BID Conditioning RegimenExperimental treatment 6 interventions

Trial outcomes

Primary outcomes

1

Non-Relapse Mortality (NRM)

Death without prior disease relapse following allogeneic peripheral blood stem cell transplantation.

Time frame
Day 100 after transplantation
2

Neutrophil Engraftment

Neutrophil engraftment following allogeneic peripheral blood stem cell transplantation.

Time frame
Through Day 100 after transplantation

Secondary outcomes

1

Risk of Relapse

Disease relapse following allogeneic peripheral blood stem cell transplantation.

Time frame
Day 100 post-transplant
2

Disease-Free Survival (DFS)

Disease-free survival following allogeneic peripheral blood stem cell transplantation.

Time frame
Day 100 post-transplant
3

Overall Survival (OS)

Overall survival following allogeneic peripheral blood stem cell transplantation.

Time frame
Day 100 post-transplant
4

Incidence of Grade II-IV Acute Graft-versus-Host Disease (GVHD)

Incidence and severity of Grade II-IV acute graft-versus-host disease following allogeneic peripheral blood stem cell transplantation.

Time frame
Day 100 post-transplant

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

This trial is not recruiting at the moment. You can still explore other options: