GVHD Prophylaxis Regimens for Blood Cancer Stem Cell Transplant

Overseen By Masumi Ueda Oshima

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Fred Hutchinson Cancer Research Center

Must not be taking: Antidepressants, others

Disqualifiers: Pregnancy, HIV, Organ dysfunction, 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: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines methods to prevent graft versus host disease (GVHD), a serious complication in blood cancer patients receiving stem cell transplants from unrelated donors. Researchers are testing two drug combinations to determine which better reduces the risk of GVHD post-transplant. The study uses lower doses of chemotherapy drugs and compares the immunosuppressants cyclosporine and sirolimus with either mycophenolate mofetil or post-transplant cyclophosphamide, a chemotherapy drug. This trial may suit individuals with blood cancers, such as certain types of leukemia or lymphoma, who qualify for a stem cell transplant and have undergone specific prior treatments. As a Phase 2 trial, the research focuses on assessing 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 whether you need to stop taking your current medications. However, it mentions that certain cytotoxic agents are not allowed within three weeks of starting the conditioning treatment, so you may need to discuss your specific medications with the trial team.

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

In earlier studies, adding sirolimus to cyclosporine and mycophenolate mofetil reduced the risk of acute graft-versus-host disease (GVHD), a condition where transplanted cells attack the patient's body. This combination did not result in any deaths from GVHD, although some serious side effects occurred.

Research has also shown that using cyclophosphamide after a transplant, along with a drug like cyclosporine, can extend periods without GVHD and relapse compared to standard treatments.

The current trial is in Phase 2, indicating that the treatments have already undergone basic safety testing. This phase focuses on evaluating the treatments' effectiveness and monitoring for additional safety concerns. Participants should be aware that while these combinations appear promising, side effects may still vary from person to person. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for GVHD prophylaxis in blood cancer stem cell transplantation because they explore different combinations of medications that might offer better outcomes. Unlike standard treatments, which often focus on just a couple of drugs, these regimens include innovative combinations of cyclophosphamide, cyclosporine, sirolimus, and mycophenolate mofetil. The unique aspect of these treatment arms is how they stagger the use of these drugs over time, tailoring the regimen based on donor compatibility (HLA-matched or mismatched). This strategic layering aims to reduce the risk of GVHD while potentially enhancing the efficacy and safety of stem cell transplants, offering hope for improved patient outcomes.

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

Research has shown that a combination of cyclosporine, sirolimus, and post-transplant cyclophosphamide, one of the treatment arms in this trial, can help patients live longer without developing graft-versus-host disease (GVHD) after a stem cell transplant. This combination also protects against certain viral infections, such as cytomegalovirus. Alternatively, another treatment arm in this trial uses mycophenolate mofetil with cyclosporine and sirolimus, which greatly reduces the chances of acute GVHD. Both drug combinations in this trial aim to lower the risk of GVHD, a serious condition where the donated cells attack the patient's body. These findings suggest that both treatment approaches are promising for reducing GVHD risks after a transplant. ^{1 6 7 8 9}

Who Is on the Research Team?

Masumi Ueda Oshima

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

Adults aged 18-50 with certain high-risk blood cancers treatable by stem cell transplant from an unrelated donor, but who can't handle high-dose transplants due to medical conditions or prior therapy. Specific criteria include having less than 5% marrow blasts for some leukemias and being in remission for others. Must not be pregnant, breastfeeding, have severe organ dysfunction or active infections unresponsive to treatment.

Inclusion Criteria

My condition is approved by the trial's lead researcher.

I have Waldenstrom's macroglobulinemia and two treatments have not worked for me.

My donor and I mismatch for two HLA class I alleles but match for HLA-DRB1 and HLA-DQ.

Exclusion Criteria

My lymphoma is fast-growing and not low grade.

My blood has at least 5% leukemia cells.

The donor will only donate bone marrow.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning and Transplantation

Patients undergo allogeneic hematopoietic stem cell transplant (HCT) at day 0 with conditioning regimen

1 week

Inpatient stay for transplantation

GVHD Prophylaxis Treatment

Patients receive GVHD prophylaxis with either mycophenolate mofetil, cyclosporine, and sirolimus or cyclosporine, sirolimus, and cyclophosphamide

Up to 52 weeks

Regular follow-up visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Follow-up at 6 months and annually thereafter

What Are the Treatments Tested in This Trial?

Interventions

• Allogeneic Hematopoietic Stem Cell Transplantation
• Cyclophosphamide
• Cyclosporine
• Mycophenolate Mofetil
• Sirolimus

Trial Overview This phase II trial tests a lower dose of chemotherapy combined with a blood stem cell transplant from an unrelated donor to treat various blood cancers. It compares two drug combinations (CSP+SIR+MMF vs CSP+SIR+PTCy) aiming to reduce graft versus host disease risk after the transplant.

How Is the Trial Designed?

Group I: Arm II (cyclosporine, sirolimus, cyclophosphamide) Experimental Treatment 4 Interventions

Patients undergo HCT at day 0. Patients with an HLA-matched unrelated donor receive cyclosporine PO BID on days 5-96 then tapered to day 150, sirolimus PO QD on days 5-150 then tapered to day 180, and cyclophosphamide IV on days 3 and 4. Patients with an HLA-mismatched donor receive cyclosporine PO BID on days 5-150 then tapered to day 180, sirolimus PO QD on days 5-180 then tapered to day 365, and cyclophosphamide IV on days 3 and 4.

Group II: Arm I (mycophenolate mofetil, cyclosporine, sirolimus) Experimental Treatment 4 Interventions

Patients undergo allogeneic HCT at day 0. Patients with an HLA-matched unrelated donor receive mycophenolate mofetil PO on days 0 to 40, cyclosporine PO every 12 hours BID on days -3 to 96 then tapered to day 150, and sirolimus PO QD on days -3 to day 150 then tapered to day 180. Patients with an HLA-mismatched donor receive mycophenolate mofetil PO on days 0-100 then tapered to day 150, cyclosporine PO BID on days -3 to 150 then tapered to day 180, and sirolimus PO QD on days -3 to 180 then tapered to day 365.

Allogeneic Hematopoietic Stem Cell Transplantation is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Allogeneic Hematopoietic Stem Cell Transplantation for:

• Primary immunodeficiency disorders
• Immune dysregulatory disorders
• Hemophagocytic lymphohistiocytosis
• Bone marrow failure syndromes
• Hemoglobinopathies

Approved in United States as Allogeneic Hematopoietic Stem Cell Transplantation for:

• Primary immunodeficiency disorders
• Immune dysregulatory disorders
• Hemophagocytic lymphohistiocytosis
• Bone marrow failure syndromes
• Hemoglobinopathies

Approved in Canada as Allogeneic Hematopoietic Stem Cell Transplantation for:

• Primary immunodeficiency disorders
• Immune dysregulatory disorders
• Hemophagocytic lymphohistiocytosis
• Bone marrow failure syndromes
• Hemoglobinopathies

Approved in Japan as Allogeneic Hematopoietic Stem Cell Transplantation for:

• Primary immunodeficiency disorders
• Immune dysregulatory disorders
• Hemophagocytic lymphohistiocytosis
• Bone marrow failure syndromes
• Hemoglobinopathies

Who Is Running the Clinical Trial?

Fred Hutchinson Cancer Research Center

Lead Sponsor

Trials

444

Recruited

148,000+

Fred Hutchinson Cancer Center

Lead Sponsor

Trials

583

Recruited

1,341,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Citations

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

Graft-versus-Host Disease Prophylaxis with ... The combination of post-transplantation cyclophosphamide and a calcineurin inhibitor led to longer GVHD-free, relapse-free survival than standard prophylaxis.

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

Effectiveness of addition of sirolimus to cyclosporine and ... Sirolimus-based graft-versus-host disease prophylaxis protects against cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation ...

3. 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 ...

4. 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.

5. sciencedirect.com sciencedirect.com/science/article/pii/S2666636721009428

and Sirolimus-Based Graft-Versus-Host-Disease ... Clinical use of PTCy has demonstrated efficacy in matched and mismatched HSCT across a wide range of patients and transplant platforms [14]. This results in low ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12203277/

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

7. ashpublications.org ashpublications.org/bloodadvances/article/8/16/4294/515903/High-dose-alemtuzumab-and-cyclosporine-vs

High-dose alemtuzumab and cyclosporine vs tacrolimus ... Although higher doses have a strong protective effect against GVHD,7,8,32-34 this often comes with increased rates of relapse, graft rejection, ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2666636725010607

Evaluation of Immunosuppression Levels and Risk of Graft ... Early immunosuppression levels in patients receiving post-transplantation cyclophosphamide-based graft-versus-host disease prophylaxis did not correlate with ...

9. haematologica.org haematologica.org/article/view/7886

A prospective randomized trial comparing cyclosporine ... The hypothesis was that the tacrolimus/sirolimus regimen would lead to less acute graft--host disease and reduced transplant-related mortality.