Early Use of Tacrolimus for Bone Marrow Transplant

Overseen By Caitlin Guzowski, MBA, MHA, CCRC

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Northside Hospital, Inc.

Disqualifiers: Poor cardiac, pulmonary, liver, renal function, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether starting Tacrolimus earlier can reduce severe immune reactions after a bone marrow transplant. The goal is to make the transplant process safer and more effective for people with blood cancers requiring a stem cell transplant. Participants will receive a combination of three treatments: Cyclophosphamide, Mycophenolate mofetil, and Tacrolimus. Ideal candidates for the trial have a blood cancer that requires a stem cell transplant and a suitable family donor. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that a combination of three drugs—tacrolimus, mycophenolate mofetil, and cyclophosphamide—in bone marrow transplants is generally safe. Specifically, using cyclophosphamide after a transplant has greatly reduced the risk of graft-versus-host disease (GVHD), where new immune cells attack the body.

One study linked this drug combination to a lower chance of cancer recurrence after the transplant, suggesting it might be both safe and effective. These studies have reported no major serious side effects, indicating that the treatment is usually well-tolerated.

This treatment is currently being tested in a Phase 2 trial, meaning it has already demonstrated some safety in earlier studies. However, further research is needed to confirm these results. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using tacrolimus early in bone marrow transplants because it offers a unique approach to preventing graft-versus-host disease (GVHD), a common complication. Unlike standard treatments that often rely on drugs like methotrexate, tacrolimus works by suppressing the immune response more precisely, potentially reducing the risk of severe GVHD. Additionally, combining tacrolimus with mycophenolate mofetil and post-transplant cyclophosphamide might enhance its effectiveness and safety profile, offering a more tailored and potentially more successful treatment option for transplant patients.

What evidence suggests that this trial's treatments could be effective in reducing Cytokine Release Syndrome?

In this trial, participants will receive a combination of three drugs—tacrolimus, mycophenolate mofetil (MMF), and cyclophosphamide—to evaluate their effectiveness in reducing the risk of graft-versus-host disease (GVHD) after bone marrow transplants. Research has shown that using these drugs together significantly decreases the chances of GVHD and leads to better overall outcomes. Specifically, cyclophosphamide administered after the transplant has lowered the risk of cancer returning and improved survival rates. This combination is now considered more effective at preventing GVHD than the current standard treatment, with fewer side effects. Overall, evidence supports the effectiveness of this treatment in managing complications after stem cell transplants. ^{2 3 6 7 8}

Who Is on the Research Team?

Melhem Solh, MD

Principal Investigator

The Blood and Marrow Transplant Group of Georgia

Are You a Good Fit for This Trial?

This trial is for individuals with blood disorders who are undergoing a specific bone marrow transplant called HLA-mismatched haploidentical transplantation. They should not have an organic affective disorder that could interfere with the study.

Inclusion Criteria

I am getting my first transplant from a donor, but I may have had a transplant using my own cells before.

I have a family donor who is a partial match and willing to donate stem cells.

I am able to care for myself but may not be able to do active work.

Exclusion Criteria

My heart's pumping ability is below 40%.

I am a woman who could get pregnant and am not using effective birth control or am currently pregnant.

Patients who have any debilitating medical or psychiatric illness that would preclude their giving informed consent or their receiving optimal treatment and follow up

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Transplantation and Early Immunosuppression

Participants undergo hematopoietic stem cell transplantation followed by early immunosuppression with Tacrolimus, MMF, and Post-Transplant Cyclophosphamide

90-180 days

Frequent visits for monitoring and administration

Follow-up

Participants are monitored for safety and effectiveness, including incidence of CRS and acute graft-versus-host disease

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Mycofenolate mofetil
• Tacrolimus

Trial Overview

The trial tests if starting Tacrolimus early, along with Cyclophosphamide and Mycofenolate mofetil after stem cell transplant, can safely reduce Cytokine Release Syndrome more effectively than current methods.

How Is the Trial Designed?

Group I: Tacrolimus + MMF + Post-Transplant Cyclophosphamide Experimental Treatment 3 Interventions

Cyclophosphamide 50mg/kg/d Days +3 and +4 after transplant Tacrolimus Day -1 to Day +90 or Day +180 after transplant MMF 15mg/kg PO TID Day 0 to Day +35

Who Is Running the Clinical Trial?

Northside Hospital, Inc.

Lead Sponsor

Trials

26

Recruited

1,100+

Published Research Related to This Trial

In a study of 12 patients undergoing unrelated donor allogeneic bone marrow transplantation, mycophenolate mofetil (MMF) combined with cyclosporine A (CsA) and methotrexate (MTX) effectively prevented acute graft versus host disease (GVHD), with only three cases of GVHD reported.

The main side effect observed was leukopenia, indicating that while MMF is effective in preventing acute GVHD, monitoring for blood cell counts is necessary for patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Combination of mycophenolate mofetil with cyclosporine A and methotrexate as acute GVHD prophylaxis after unrelated donor allogeneic bone marrow transplantation]. Huang, H., Lin, M., Meng, H., et al.[2016]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/33799685/

Post-Transplant Cyclophosphamide and Tacrolimus ...

Recently, posttransplant cyclophosphamide (PTCy) given after a bone marrow transplant significantly reduced GVHD-incidence, while PTCy given ...

2.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa2215943

Post-Transplantation Cyclophosphamide-Based Graft ...

Data from the CIBMTR suggest that the combination of mycophenolate mofetil and cyclosporine led to outcomes with respect to GVHD and overall ...

3.

sciencedirect.com

sciencedirect.com/science/article/pii/S0006497121067690

722.Allogeneic Transplantation: Acute and Chronic GVHD, ...

The purpose of this study is to evaluate outcomes using PTCy, TAC, and MMF for GVHD prophylaxis in MRD and MUD stem cell recipients who have ALL.

4.

astctjournal.org

astctjournal.org/article/S2666-6367(22)01331-8/fulltext

Mycophenolate Mofetil: A Friend or a Foe with Post- ...

Post-transplantation cyclophosphamide (PTCy)/tacrolimus (Tac)/mycophenolate mofetil (MMF) was associated with a lower risk of relapse, better ...

5.

hopkinsmedicine.org

hopkinsmedicine.org/news/newsroom/news-releases/2023/06/study-sets-new-standard-for-graft-versus-host-disease-prevention-after-stem-cell-transplant

Study Sets New Standard for Graft-Versus-Host Disease ...

The new standard is more effective at preventing GVHD and came with less side effects, compared with the current gold standard.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7998305/

Post-Transplant Cyclophosphamide and Tacrolimus ...

Recently, posttransplant cyclophosphamide (PTCy) given after a bone marrow transplant significantly reduced GVHD-incidence, while PTCy given ...

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03959241

Study Details | NCT03959241 | TAC/MTX vs. TAC/MMF/ ...

The goal of this protocol is to test the primary hypothesis that the engraftment stool microbiome diversity predicts one-year non-relapse mortality in patients ...

8.

sciencedirect.com

sciencedirect.com/science/article/pii/S2666636723017116

Post-Transplantation Cyclophosphamide and Tacrolimus ...

This study compared the efficacy of graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (PTCy) and tacrolimus (Tac) ...