Cyclophosphamide + Tacrolimus + Ruxolitinib for Leukemia

Overseen By The Ohio State University Comprehensive Cancer Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Hannah Choe, MD

Must not be taking: Ruxolitinib, Immune checkpoint inhibitors

Disqualifiers: Prior allogeneic transplant, Active CNS involvement, Uncontrolled infections, HIV with detectable viral load, Uncontrolled hepatitis, Recent thrombosis, Pregnancy, Serious medical or psychiatric illness, Prior malignancies, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the effectiveness of a combination of three drugs—cyclophosphamide, tacrolimus, and ruxolitinib (a JAK inhibitor)—in individuals with certain types of leukemia. The goal is to assess whether this combination can prevent complications after a stem cell transplant. The study seeks participants with acute leukemia or myelodysplasia, who have a limited number of cancer cells in their bone marrow, and are preparing for a stem cell transplant using a matched donor. As a Phase 2 trial, the 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 if you need to stop taking your current medications. However, it mentions that certain maintenance therapies are allowed, so it's best to discuss your specific medications with the trial team.

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

Research has shown that using low-dose cyclophosphamide with ruxolitinib is generally safe and well-tolerated. Previous studies on this combination for preventing graft-versus-host disease (GVHD) found it both safe and effective. Patients taking ruxolitinib at 5 mg twice a day, along with other medications, experienced positive outcomes without major side effects.

Additionally, ruxolitinib has been safely used in other transplant situations to help prevent GVHD. Cyclophosphamide, already approved by the FDA for other uses, is well-known in the medical community. Using it in low doses aims to minimize possible side effects.

While all treatments carry some risks, current evidence supports this combination as a safe option for patients undergoing stem cell transplants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining cyclophosphamide, tacrolimus, and ruxolitinib for leukemia because this approach aims to prevent graft-versus-host disease (GVHD) more effectively after a transplant. Unlike traditional treatments that often use just cyclophosphamide and tacrolimus, this regimen includes ruxolitinib, which targets specific pathways involved in GVHD, potentially reducing the risk and severity of this condition. By integrating ruxolitinib, a JAK inhibitor, into the regimen, this treatment could offer a more tailored and potentially less toxic approach to managing post-transplant complications, improving patient outcomes.

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

In this trial, participants will receive a combination of cyclophosphamide, tacrolimus, and ruxolitinib to prevent graft-versus-host disease (GVHD) following stem cell transplants. Research has shown that cyclophosphamide and ruxolitinib together can effectively prevent GVHD. Studies have found that this combination is well-tolerated and helps control GVHD rates. Specifically, one study found that two-thirds of patients taking ruxolitinib were still alive three years after starting the treatment. Ruxolitinib, when used with other medicines, has been safely used to prevent GVHD, showing promise as a preventive treatment. Cyclophosphamide has also successfully reduced GVHD in similar situations. ^{4 6 7 8 9}

Who Is on the Research Team?

Hannah Choe, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with certain blood disorders like leukemia or myelodysplastic syndrome, who are undergoing a stem cell transplant. Participants should be suitable for high-dose chemotherapy before the transplant.

Inclusion Criteria

My heart pumps well, with an ejection fraction of 45% or more.

My kidneys are functioning well.

My liver tests are within the required range.

Exclusion Criteria

I have had cancer before, but it fits the exceptions.

I have had a transplant from another person.

My cancer has spread to my brain or spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Transplantation and Initial Treatment

Participants undergo myeloablative allogeneic peripheral blood stem cell transplantation and receive post-transplant cyclophosphamide, tacrolimus, and ruxolitinib for GVHD prophylaxis.

Up to 28 days

Multiple visits for transplantation and initial treatment

Extended Treatment

Participants continue receiving ruxolitinib and tacrolimus with tapering as per protocol. Ruxolitinib is administered up to Day 180 or 365 post-transplant depending on cohort.

Up to 12 months

Follow-up

Participants are monitored for safety, effectiveness, and GVHD-free survival post-treatment.

Up to 2 years

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Ruxolitinib

Trial Overview The study tests a combination of low dose cyclophosphamide, tacrolimus, and ruxolitinib as prevention against graft-versus-host disease after intense chemo and stem cell transplant. It's an open-label pilot study without random assignment to groups.

How Is the Trial Designed?

Group I: Cohort 2 (dose expansion) Experimental Treatment 5 Interventions

Patients will receive post-transplant cyclophosphamide 25 mg/kg on Days +3 and +4, tacrolimus, and ruxolitinib for GVHD prophylaxis. Ruxolitinib will be dosed as ruxolitinib IR 5 mg po qD (on fluconazole, 5 mg po BID not on fluconazole) starting Day -1 until Day +28 and neutrophil engraftment and then increase to ruxolitinib IR 5 mg po BID (on fluconazole,10 mg po BID not on fluconazole) for up to 12 months. Tacrolimus will be tapered after Day +90 per institutional guidelines. Patients will receive ruxolitinib up to Day 365 post-transplant. Ruxolitinib will be tapered over 2-3 months depending on the starting dose at time of taper.

Group II: Cohort 1 (Feasibility) Experimental Treatment 5 Interventions

Patients will receive post-transplant cyclophosphamide 25 mg/kg on Days +3 and +4, tacrolimus, and ruxolitinib for GVHD prophylaxis. Ruxolitinib will be dosed as ruxolitinib IR 5 mg po qD (on fluconazole, 5 mg po BID not on fluconazole) starting Day -1 until Day +28 and neutrophil engraftment and then increase to ruxolitinib IR 5 mg po BID (on fluconazole,10 mg po BID not on fluconazole) for up to 12 months. Tacrolimus will be tapered after Day +90 per institutional guidelines. Patients will receive ruxolitinib up to Day 180 posttransplant. Ruxolitinib will be tapered over 2-3 months depending on the starting dose at time of taper.

Who Is Running the Clinical Trial?

Hannah Choe, MD

Lead Sponsor

Trials

1

Recruited

2+

Incyte Corporation

Industry Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12283849/

Ruxolitinib treatment outcomes in acute graft-versus-host ... Two-thirds of the patients were able to discontinue CSs, and two-thirds were estimated to be alive at three years from the initiation of ruxolitinib treatment.

2. astctjournal.org astctjournal.org/article/S2666-6367(25)01372-7/fulltext?rss=yes

Safe and Effective Addition of Ruxolitinib to Graft-versus- ... In the meantime, this report suggests that Rux 5 mg twice daily is a safe and effective GVHD prophylactic dose when combined with Tac/MTX in the setting of RIC ...

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 ... Secondary outcomes include the incidence and severity of GVHD, hematologic and immune recovery, donor chimerism, relapse, non-relapse mortality, ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06756152

Study Details | NCT06756152 | Preventing of GVHD with ... The use of post-transplant cyclophosphamide for the prevention of GVHD during allogeneic HSCT from unrelated and haploidentical donors has reduced the incidence ...

5. 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 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12399409/

Ruxolitinib and decitabine plus a busulfan ... The overall survival (OS) and disease-free survival (DFS) rates at 1 year were 70.3% and 62.2%, respectively (3). Our previous research revealed ...

7. 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 ...

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

Safe and Effective Addition of Ruxolitinib to Graft-versus- ... In the meantime, this report suggests that Rux 5 mg twice daily is a safe and effective GVHD prophylactic dose when combined with Tac/MTX in the setting of RIC ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0966327423001958

Efficacy and safety in early application of Ruxolitinib for ... Our results suggest that the early application of ruxolitinib could safely and effectively prevent the occurrence of GVHD after allo-HSCT for the high-risk ALL ...