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

Trial Summary

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.

What data supports the effectiveness of the drug combination Cyclophosphamide, Mycophenolate mofetil, and Tacrolimus for bone marrow transplant?

Research shows that the combination of Mycophenolate mofetil and Tacrolimus is effective in managing graft-versus-host disease (GVHD), a common complication after bone marrow transplants. In one study, 46% of patients with chronic GVHD showed improvement with this combination, suggesting it may help in similar transplant scenarios. ^{1 2 3 4 5}

Is the combination of Tacrolimus and Mycophenolate Mofetil safe for use in humans?

The combination of Tacrolimus and Mycophenolate Mofetil has been generally well tolerated in humans, though some patients experienced serious side effects like neurotoxicity (nerve damage) and nephrotoxicity (kidney damage). Most adverse events were manageable with supportive care, suggesting that the treatment is relatively safe with proper monitoring. ^{1 2 6 7 8}

How is the drug combination of Cyclophosphamide, Mycophenolate mofetil, and Tacrolimus unique for bone marrow transplant patients?

This drug combination is unique because Tacrolimus, a powerful immunosuppressant, is used early to prevent graft-versus-host disease (GVHD), which is a common complication after bone marrow transplants. Tacrolimus is more effective than cyclosporine in reducing acute GVHD, and when combined with Mycophenolate mofetil, it offers a promising approach for patients who do not respond to standard therapies. ^{1 2 4 9 10}

What is the purpose of this trial?

To evalute the safety and efficacy in reducing Cytokine Release Syndrome after hematopoietic stem cell transplantation by introducing immunosuppression earlier in the transplant process

Research Team

Melhem Solh, MD

Principal Investigator

The Blood and Marrow Transplant Group of Georgia

Eligibility Criteria

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 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.

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. China pubmed.ncbi.nlm.nih.gov

[Mycophenolate mofetil in treatment of graft-versus-host disease after allogeneic hematopoietic cell transplantation: analysis of 44 cases]. [2016]

2. United States pubmed.ncbi.nlm.nih.gov

A pilot study of tacrolimus and mycophenolate mofetil graft-versus-host disease prophylaxis in childhood and adolescent allogeneic stem cell transplant recipients. [2016]

3. China 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]. [2016]

4. England pubmed.ncbi.nlm.nih.gov

Salvage therapy for refractory chronic graft-versus-host disease with mycophenolate mofetil and tacrolimus. [2019]

5. Japan pubmed.ncbi.nlm.nih.gov

Mycophenolate mofetil combined with tacrolimus and minidose methotrexate after unrelated donor bone marrow transplantation with reduced-intensity conditioning. [2021]

6. Japan pubmed.ncbi.nlm.nih.gov

Use of mycophenolate mofetil in patients received allogeneic hematopoietic stem cell transplantation in Japan. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Efficacy of mycophenolate mofetil in the treatment of chronic graft-versus-host disease. [2016]

8. United States pubmed.ncbi.nlm.nih.gov

Tacrolimus/methotrexate vs tacrolimus/reduced-dose methotrexate/mycophenolate for graft-versus-host disease prevention. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Tacrolimus: a new agent for the prevention of graft-versus-host disease in hematopoietic stem cell transplantation. [2013]

10. England pubmed.ncbi.nlm.nih.gov

Phase III study comparing tacrolimus (FK506) with cyclosporine for graft-versus-host disease prophylaxis after allogeneic bone marrow transplantation. [2013]