Drug Combinations for Acute Graft-versus-Host Disease

Overseen By Uday Popat, MBA,MD

Age: 65+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: HIV, Acute promyelocytic leukemia, CNS involvement, 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

Duration: 12 weeks

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different drug combinations can prevent acute graft-versus-host disease, a complication where donor cells attack the recipient's body, after a stem cell transplant. It compares two combinations: one uses cyclophosphamide, sirolimus (an immunosuppressant), and mycophenolate mofetil (an immunosuppressant), while the other uses cyclophosphamide, sirolimus, and ruxolitinib (a Janus kinase inhibitor). Individuals with conditions such as acute myeloid leukemia, myelodysplastic syndrome, or chronic myelomonocytic leukemia who have undergone a stem cell transplant may qualify if they have a suitable donor and adequate organ function. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor to get specific guidance based on your situation.

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

Research has shown that the drug combination of cyclophosphamide, sirolimus, and mycophenolate mofetil (MMF) is generally well-tolerated. In studies, patients using this combination did not experience deaths related to graft-versus-host disease (GVHD). However, some severe side effects were reported, though specific details are not available.

For the combination of cyclophosphamide, sirolimus, and ruxolitinib, research indicates it is both effective and safe. One study found that patients using ruxolitinib had a survival rate of about 64% over three years, suggesting it is well-tolerated in real-world settings. While some side effects might occur, the treatment seems manageable for most patients.

Both drug combinations are being tested to assess their effectiveness in preventing GVHD after stem cell transplants. Although detailed information on side effects isn't fully available, evidence suggests these treatments are generally safe to use. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for acute graft-versus-host disease (GVHD) because they combine drugs in innovative ways to target the condition more effectively. Unlike many existing treatments that primarily use steroids to control inflammation, these combinations use Cyclophosphamide and Sirolimus to modulate the immune response. Additionally, Ruxolitinib, a JAK inhibitor, is used in one arm to specifically block pathways that contribute to GVHD, offering a targeted approach. These combinations aim to reduce the severity of GVHD with potentially fewer side effects than traditional therapies.

What evidence suggests that this trial's treatments could be effective for preventing GVHD?

In this trial, participants will receive different drug combinations to manage acute graft-versus-host disease (GVHD). One treatment arm combines cyclophosphamide, sirolimus, and mycophenolate mofetil (MMF). Research has shown that this combination may help prevent acute GVHD. Specifically, one study found that 49% of patients survived without GVHD or disease recurrence after three years, compared to only 14% with standard treatment. Another study found that this combination reduced moderate-to-severe chronic GVHD to just 3%.

Another treatment arm includes adding ruxolitinib to cyclophosphamide and sirolimus. In real-world use, ruxolitinib showed a 64.1% survival rate at three years and had a high response rate in patients with severe acute GVHD, with 84% showing improvement within 28 days. Both treatment combinations in this trial offer hope for better managing GVHD after a transplant. ^{1 6 7 8 9}

Who Is on the Research Team?

Uday Popat, MBA,MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for people aged 65-75 with Acute Myeloid Leukemia or related conditions, who have a suitable stem cell donor. They must be in good health with proper organ function and agree to use contraception. It's not for those with HIV, high-risk comorbidities, pregnancy, certain leukemia types, uncontrolled diseases like infections or heart issues.

Inclusion Criteria

Voluntary signing of an informed consent

Agreement to use adequate contraception for women of child-bearing potential and men throughout the study period

My liver, kidneys, lungs, and heart are functioning well.

Exclusion Criteria

Positive for HIV

Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) score of >5

Pregnancy or breastfeeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive post-transplant cyclophosphamide, sirolimus, and either MMF or ruxolitinib to prevent GVHD

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Mycophenolate Mofetil
• Ruxolitinib
• Sirolimus

Trial Overview The study compares two drug combinations after a stem cell transplant: cyclophosphamide with sirolimus and either MMF (Mycophenolate Mofetil) or ruxolitinib. The aim is to see which combo better prevents Graft Versus Host Disease (GVHD), a common post-transplant complication.

How Is the Trial Designed?

Group I: 01B:Treatment With Post-Transplant Cyclophosphamide (PTCy),Sirolimus and Ruxolitinib Experimental Treatment 1 Intervention

5 mg PO every 12 hours

Group II: 01A:Treatment With Post-Transplant Cyclophosphamide (PTCy), Sirolimus and MMF Experimental Treatment 1 Intervention

15 mg/kg/dose (max: 1,000mg/dose) IV/PO three times daily

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2503189

Graft-versus-Host Disease Prophylaxis with ... GVHD-free, relapse-free survival at 3 years was 49% (95% CI, 36 to 61) with experimental prophylaxis and 14% (95% CI, 6 to 25) with standard ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41043099/

Sirolimus and Cyclosporine With Post-Transplant ... Purpose: To determine whether sirolimus (SIR) and cyclosporine (CSP) combined with post-transplantation cyclophosphamide (PTCy), after ...

3. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO-25-01238

Sirolimus and Cyclosporine With Post-Transplant ... One-year estimates for secondary end points were as follows: moderate-to-severe cGVHD, 3% (95% CI, 1% to 9%) versus 33% (95% CI, 22% to 44%); ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05436418

Study Details | NCT05436418 | The Lowest Effective Dose ... The Lowest Effective Dose of Post-Transplantation Cyclophosphamide in Combination With Sirolimus and Mycophenolate Mofetil as Graft-Versus-Host Disease ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6686903/

Effectiveness of addition of sirolimus to cyclosporine and ... Adding sirolimus to cyclosporine and mycophenolate mofetil resulted in a significantly lower incidence of acute GVHD. Based on these results, the combination of ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3163055/

Sirolimus and Mycophenolate Mofetil as Graft-versus-Host ... MMF and sirolimus GVHD prophylaxis did not reduce the risk of acute GVHD, however, there were no GVHD-related deaths. The severe toxicities in the patients ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01220297

Sirolimus & Mycophenolate Mofetil as GvHD Prophylaxis in ... This study will report the toxicities associated with this drug combination. For all treatments and procedures, Study Day is based on the day of HSCT as Day 0.

8. ashpublications.org ashpublications.org/bloodadvances/article/9/16/4336/537897/A-prospective-clinical-trial-of-GVHD-prophylaxis

A prospective clinical trial of GVHD prophylaxis with ... PTCy has generally not decreased mild acute GVHD, however it has been shown to decrease grade 3/4 GVHD when compared with tacrolimus and ...

9. ctrjournal.org ctrjournal.org/journal/view.html?uid=2319&vmd=Full

Comparing drug combinations for graft-versus-host ... The results demonstrated that certain GVHD prophylaxis drug combinations, particularly those including cyclosporine, may be relatively ineffective.