Cyclophosphamide + Ruxolitinib for Graft-versus-Host Disease Prophylaxis

Overseen By Medical College of Wisconsin Cancer Center Clinical Trials Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Medical College of Wisconsin

Disqualifiers: Prior allogeneic HCT, Liver dysfunction, Renal impairment, Cardiac 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: Unknown

56 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two medications, Cyclophosphamide (a chemotherapy drug) and Ruxolitinib (a Janus kinase inhibitor), to determine their effectiveness in preventing graft-versus-host disease (GVHD) in older adults who have received a stem cell transplant from a matched donor. The goal is to assess whether these drugs can safely and effectively reduce the risk of GVHD, a condition where the donated cells attack the recipient's body. Individuals who have had certain types of blood cancers, are in remission, and have a matched stem cell donor may be suitable candidates for this study. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

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 using cyclophosphamide and ruxolitinib together to prevent graft-versus-host disease (GVHD) is generally safe and well-tolerated. Studies have found this treatment to have low toxicity, with patients experiencing good control over both early and later stages of GVHD.

However, some side effects require attention. Cyclophosphamide can sometimes slow the growth of new blood cells, increase infection risk, and affect organs. Despite these potential issues, the treatment remains safe overall. Ruxolitinib, when used around the time of transplant, has been manageable and tolerable.

In summary, while some risks exist, this drug combination is considered safe for many patients. It's important for individuals to consult healthcare providers to understand the specific risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of cyclophosphamide and ruxolitinib for preventing graft-versus-host disease (GVHD) because it introduces a novel approach by targeting specific pathways that current treatments don't address. Unlike traditional regimens that often rely heavily on general immunosuppressants, ruxolitinib specifically inhibits the JAK1/2 pathway, which plays a crucial role in the immune response involved in GVHD. This targeted action could potentially offer a more effective and less toxic option for patients. Additionally, the use of cyclophosphamide shortly after transplant aims to selectively eliminate alloreactive T cells, reducing the risk of GVHD while preserving graft function. This combined approach offers a promising enhancement to existing therapies, potentially improving patient outcomes and quality of life.

What evidence suggests that Cyclophosphamide and Ruxolitinib might be effective for graft-versus-host disease?

Research has shown that using cyclophosphamide and ruxolitinib together, as studied in this trial, can help prevent graft-versus-host disease (GVHD) after a stem cell transplant. Studies have found that this combination effectively controls both short-term and long-term GVHD, with a low risk of recurrence. Most people tolerate this treatment well, as it usually doesn't cause severe side effects. Evidence indicates that after one year, many patients live without GVHD-related issues. Overall, this treatment approach appears promising for managing GVHD in patients undergoing stem cell transplants. ^{2 3 6 7 8}

Who Is on the Research Team?

Sameem M. Abedin

Principal Investigator

Medical College of Wisconsin

Are You a Good Fit for This Trial?

Adults with certain blood cancers who are in remission can join this trial if they have a matched stem cell donor and meet health criteria like good performance status, normal organ function, and no recent other cancers. They must agree to contraception use.

Inclusion Criteria

I am scheduled for a milder form of pre-transplant treatment.

Ability to understand a written informed consent document, and the willingness to sign it

I have a stem cell donor who is a perfect match for me.

Exclusion Criteria

My lung function tests are below 50% of what's expected.

I have had a bone marrow transplant or CAR-T cell therapy before.

Pregnant or lactating subjects

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning and Transplant

Participants undergo reduced intensity conditioning and receive an 8/8-matched peripheral blood stem cell transplant on Day 0

1 week

GVHD Prophylaxis

Participants receive cyclophosphamide on Day +3 and +4, tacrolimus from Day +5 through Day +180, mycophenolate mofetil from Day +5 through Day +35, and ruxolitinib starting after engraftment through one year post-transplant

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments for acute and chronic GVHD and overall survival

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Ruxolitinib

Trial Overview The study tests a combination of low-dose Cyclophosphamide (PTCy) and Ruxolitinib for preventing GVHD in older adults receiving stem cell transplants from matched donors, using reduced intensity conditioning therapy.

How Is the Trial Designed?

Group I: Graft-versus-host disease prophylaxis Experimental Treatment 4 Interventions

Following reduced intensity conditioning and 8/8-matched peripheral blood transplant on Day 0, all patients will receive a GVHD prophylaxis post-transplant composed of the following: (i) cyclophosphamide administered at 25 mg/kg on Day +3 and +4, (ii) tacrolimus beginning on Day +5 and through Day +180 and administered with a trough target of 5-10 ng/ml through Day +90 and tapered thereafter; (iii) mycophenolate mofetil (MMF) administered at 15 mg/kg thrice daily beginning on Day +5 through Day +35; and (iv) ruxolitinib administered at 5 mg twice daily starting after engraftment (between Days +30 and +60) and continuing through one year post transplant.

Cyclophosphamide is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Published Research Related to This Trial

Ruxolitinib prophylaxis showed a 41.2% incidence of acute graft-versus-host disease (aGVHD) in patients after modified donor lymphocyte infusion, indicating it can help reduce the severity of aGVHD in high-risk leukemia patients post-transplant.

Among the 17 patients studied, 58.8% achieved a complete response, suggesting that ruxolitinib may effectively maintain the graft-versus-leukemia (GVL) effect while managing aGVHD, despite a median follow-up of only 8 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib on acute graft-versus-host disease prophylaxis after modified donor lymphocyte infusion. Tang, Y., Yang, D., Xie, R., et al.[2023]

In a study of 29 patients with graft versus host disease (GvHD), Ruxolitinib exposure was found to be significantly higher than in myelofibrosis patients, indicating altered drug metabolism in GvHD.

Increased Ruxolitinib levels were linked to reduced drug clearance and the use of CYP3A4 or CYP2C9 inhibitors, suggesting that higher trough concentrations may indicate a risk of toxicity and necessitate careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib exposure in patients with acute and chronic graft versus host disease in routine clinical practice-a prospective single-center trial. Isberner, N., Kraus, S., Grigoleit, GU., et al.[2022]

Ruxolitinib, an oral JAK1/JAK2 inhibitor, was approved by the FDA for treating steroid-refractory acute graft-versus-host disease (GVHD) based on promising results from the Phase II REACH1 trial.

The drug shows potential not only for treating SR acute GVHD but also for preventing GVHD and possibly serving as a first-line therapy, highlighting its versatility in managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib for the treatment of graft-versus-host disease. Ali, H., Salhotra, A., Modi, B., et al.[2021]

Ruxolitinib (RUX) was well tolerated and led to significant improvements in chronic graft-versus-host disease (GVHD) symptoms in 19 allograft recipients, with high response rates in various affected areas, such as oral (92%) and cutaneous (82%) regions.

The treatment allowed for a reduction or discontinuation of steroid use in 68% of patients, demonstrating RUX's effectiveness as a steroid-sparing agent in managing chronic GVHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib: a steroid sparing agent in chronic graft-versus-host disease. Khoury, HJ., Langston, AA., Kota, VK., et al.[2021]

Ruxolitinib, a drug used to treat steroid-refractory acute graft-versus-host disease in allogeneic hematopoietic cell transplantation (HCT) recipients, can lead to acute hypoxemic respiratory failure upon discontinuation, as observed in three patients within three months of stopping the medication.

Reinitiating ruxolitinib along with systemic corticosteroids resulted in rapid clinical improvement for these patients, highlighting the need for careful management of ruxolitinib dosing and discontinuation to avoid serious respiratory complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypoxemic Respiratory Failure Following Ruxolitinib Discontinuation in Allogeneic Hematopoietic Cell Transplantation Recipients. Anandappa, AJ., Hobbs, GS., Dey, BR., et al.[2021]

In a study of 8 patients with acute or chronic graft versus host disease (GVHD) who were unresponsive to standard treatments, ruxolitinib demonstrated a high overall response rate of 85%, with 50% achieving complete response.

Ruxolitinib was well-tolerated, indicating it could be a promising rescue therapy for patients suffering from refractory GVHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Compassionate use of ruxolitinib in acute and chronic graft versus host disease refractory both to corticosteroids and extracorporeal photopheresis. Sarmiento Maldonado, M., Ramírez Villanueva, P., Bertín Cortes-Monroy, P., et al.[2022]

In a study of 20 pediatric and young adult patients with chronic graft versus host disease (cGVHD), ruxolitinib showed a 70% overall response rate, with 2 patients achieving complete response and 12 achieving partial response after a median of 48 days.

The dosing strategy of ruxolitinib was effective in inhibiting JAK signaling, as indicated by decreased phosphorylation of STAT5 in lymphocytes, although some patients experienced side effects like neutropenia and infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib for the Treatment of Chronic GVHD and Overlap Syndrome in Children and Young Adults. Wang, YM., Teusink-Cross, A., Elborai, Y., et al.[2022]

In a retrospective study of 17 patients with severe graft-versus-host disease (GVHD) who were unresponsive to corticosteroids and other treatments, ruxolitinib demonstrated an 80% overall response rate in acute GVHD, with 40% achieving complete remission.

Ruxolitinib also showed a 79% response rate in chronic GVHD, indicating its potential as an effective rescue therapy; however, mortality in acute GVHD patients remained high at 40%, highlighting the need for improved treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A real life use of ruxolitinib in patients with acute and chronic graft versus host disease refractory to corticosteroid treatment in Latin American patients. Sarmiento, M., Jara, V., Soto, K., et al.[2021]

In a study of 14 patients with myelofibrosis who received allogeneic hematopoietic cell transplantation after treatment with ruxolitinib, 71.4% experienced relief from myelofibrosis-related symptoms, and 64% had a significant reduction in spleen size.

Ruxolitinib treatment prior to transplantation was associated with a high engraftment rate of 93% and may improve outcomes by reducing inflammatory cytokines, potentially lowering the risk of graft failure and acute graft-versus-host disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic hematopoietic cell transplantation for myelofibrosis in patients pretreated with the JAK1 and JAK2 inhibitor ruxolitinib. Jaekel, N., Behre, G., Behning, A., et al.[2021]

Citations

1. astctjournal.org astctjournal.org/article/S2666-6367(25)01372-7/fulltext

Safe and effective addition of ruxolitinib to graft-versus-host ... Figure 1 Outcomes for patients treated with ruxolitinib as part of graft-versus-host disease (GVHD) prophylaxis. (A) The proportion of patients ...

2. gvhdhub.com gvhdhub.com/medical-information/post-transplant-cyclophosphamide-and-ruxolitinib-as-gvhd-prophylactic-regimen-in-patients-with-primary-or-secondary-myelofibrosis

Post-transplant cyclophosphamide and ruxolitinib as ... This study showed that the combination of PTCy and ruxolitinib was well tolerated and provided a promising control of GvHD rates associated with ...

3. ashpublications.org ashpublications.org/thehematologist/article/doi/10.1182/hem.V22.6.2025610/547776/PROGRESS-IV-Will-Ruxolitinib-Emerge-as-an

Will Ruxolitinib Emerge as an Alternative to Post-Transplant ... Although highly effective in reducing GVHD, PTCy can be associated with delayed engraftment and an increased risk of infections and organ ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32325461/

A Prospective Pilot Study of Graft-versus-Host Disease ... GVHD prophylaxis with PTCy and ruxolitinib is associated with low toxicity, good acute and chronic GVHD control, and low relapse incidence.

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa2215943

Post-Transplantation Cyclophosphamide-Based Graft ... At 1 year, the adjusted GVHD-free, relapse-free survival was 52.7% (95% CI, 45.8 to 59.2) with experimental prophylaxis and 34.9% (95% CI, 28.6 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05622318

NCT05622318 | De-escalated Cyclophosphamide (PTCy) ... This is an open-label phase 2 study designed to explore the efficacy and safety of low-dose PTCy-ruxolitinib GVHD prophylaxis in older adults undergoing ...

7. ascopubs.org ascopubs.org/doi/10.1200/OA-25-00020

Phase II Study of Peri- and Post-Transplant Ruxolitinib for ... Peri- and post-transplant ruxolitinib is feasible, safe, and well tolerated for patients with MF. Prolonged ruxolitinib after allogeneic ...

8. targetedonc.com targetedonc.com/view/ruxolitinib-plus-post-transplant-cyclophosphamide-controls-gvhd-in-myelofibrosis

Ruxolitinib Plus Post-Transplant Cyclophosphamide ... In this study, we evaluated ruxolitinib as a bridge, relapse, and GVHD prevention agent in patients with myelofibrosis.