Cyclophosphamide-Based Prophylaxis for Leukemia

(ACCELERATE Trial)

Recruiting at 2 trial locations

Overseen By Sarah Smith, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Center for International Blood and Marrow Transplant Research

Disqualifiers: Prior transplant, Pregnancy, Infections, 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: 4-6 weeks

358 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to identify the best drug combination to prevent graft-versus-host disease (GVHD), a common complication after a stem cell transplant from an unrelated donor with a different blood type. Participants will receive either a new drug combination, including cyclophosphamide (a chemotherapy drug), or the standard treatment. They will attend regular check-ups and tests. This study targets individuals with specific types of leukemia or myelodysplastic syndromes (MDS) who have a partially matched donor and no active disease in their blood or organs. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in GVHD prevention.

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. 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 combination of cyclophosphamide, mycophenolate mofetil, and tacrolimus has been studied for safety. Some studies suggest this combination might help people live longer without experiencing graft-versus-host disease (GVHD), a positive outcome. However, risks exist. For instance, using these drugs together can slow the growth of new blood cells after a transplant, potentially increasing the risk of infections and other side effects.

Cyclophosphamide is already used in other treatments, so doctors have extensive experience with it, providing some reassurance about its safety. However, individual reactions can vary. Discuss any concerns with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for leukemia involve chemotherapy drugs, but researchers are excited about cyclophosphamide because it offers a promising approach for prophylaxis, or prevention, of the disease. Unlike many standard treatments that target leukemia after it has developed, cyclophosphamide may help in preventing the onset of leukemia in at-risk individuals. This drug works by suppressing the immune system in a specific way, potentially stopping leukemia cells from multiplying before they become problematic. By focusing on prevention, cyclophosphamide could revolutionize how we approach leukemia, shifting from treatment to prevention and potentially improving long-term outcomes for patients.

What evidence suggests that this trial's treatments could be effective for preventing graft-versus-host disease?

Research has shown that a combination of three drugs—cyclophosphamide, tacrolimus, and mycophenolate mofetil—may help prevent graft-versus-host disease (GVHD) after stem cell transplants. In this trial, participants in the ACCEL-001 and ACCEL-002 arms will receive different interventions involving these drugs. Studies have found that using cyclophosphamide with these drugs can lead to fewer relapses and better survival rates. Specifically, one study reported that only 4% of patients died from causes other than relapse after 36 months. Another study found that overall survival rates improved when cyclophosphamide was used with tacrolimus and mycophenolate mofetil. These findings suggest that this drug combination might effectively prevent GVHD in transplant patients. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for people with certain blood cancers who need a stem cell transplant from an unrelated donor with different blood cells. They must be willing to follow the study plan, have less than 10% cancer cells in their bone marrow, and meet specific health criteria like good heart function.

Inclusion Criteria

My MDS has less than 10% blasts in the bone marrow and no circulating blasts.

My heart's pumping ability is at least 45%.

I am scheduled for a stem cell transplant with a near-matched donor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning

Participants undergo myeloablative or reduced-intensity conditioning prior to transplant

1-2 weeks

Transplantation

Participants receive mismatched unrelated donor peripheral blood stem cell transplantation

1 week

Treatment

Participants receive post-transplant cyclophosphamide-based GVHD prophylaxis and are assigned to either the standard or new drug combination

4-6 weeks

Follow-up

Participants are monitored for safety and effectiveness, including assessments of graft-versus-host disease-free survival, infection-free survival, and other outcomes

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Mycophenolate mofetil
• Tacrolimus

Trial Overview Researchers are testing new drug combinations against standard ones to prevent graft-versus-host disease after a stem cell transplant. Participants will receive drugs post-transplant, attend regular check-ups, complete well-being surveys, and provide blood and stool samples.

How Is the Trial Designed?

Group I: Control/SOC Experimental Treatment 18 Interventions

Shared comparator control group

Group II: ACCEL-002 Experimental Treatment 21 Interventions

Intervention 2

Group III: ACCEL-001 Experimental Treatment 19 Interventions

Intervention 1

Who Is Running the Clinical Trial?

Center for International Blood and Marrow Transplant Research

Lead Sponsor

Trials

40

Recruited

200,190,000+

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

National Marrow Donor Program

Collaborator

Trials

63

Recruited

202,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7998305/

Post-Transplant Cyclophosphamide and Tacrolimus ... After a 36-month median follow-up, NRM was 4%; median event-free survival (EFS) and overall survival (OS) had yet to occur. One- and two-year ...

2. nature.com nature.com/articles/s41409-024-02331-1

a study from the acute leukemia working party (EBMT) Our study demonstrates similarly favorable OS and GRFS with both TAC and CSA combined with PT-Cy/MMF. TAC was associated with less severe acute ...

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

Post-Transplantation Cyclophosphamide-Based Graft ... A phase 2 study indicated the potential superiority of a post-transplantation regimen of cyclophosphamide, tacrolimus, and mycophenolate mofetil.

4. astctjournal.org astctjournal.org/article/S2666-6367(22)01331-8/fulltext

Mycophenolate Mofetil: A Friend or a Foe with Post- ... Post-transplantation cyclophosphamide (PTCy)/tacrolimus (Tac)/mycophenolate mofetil (MMF) was associated with a lower risk of relapse, better ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1083879116312149

Post-Transplant Cyclophosphamide and Tacrolimus ... This study explored the performance of PTCy infusion, measured by transplant morbidity and outcome, when added to tacrolimus/mofetil mycophenolate (T/MMF) as ...

6. 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.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT00255710

Study Details | NCT00255710 | Cyclophosphamide and/or ... This phase I trial is studying cyclophosphamide and/or mycophenolate mofetil with or without tacrolimus to see which is the best regimen in treating patients.

8. ash.confex.com ash.confex.com/ash/2023/webprogram/Paper174821.html

Paper: Post-Transplant Cyclophosphamide, Tacrolimus or ... Recently, the BMT CTN 1703 phase III study compared post-transplant cyclophosphamide with tacrolimus with mycophenolate mofetil (PTCy/TAC/MMF) ...