20 Participants Needed

Stem Cell Transplant for Myelofibrosis

RB
Overseen ByRachel B. Salit
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: Fred Hutchinson Cancer Research Center
Must be taking: JAK inhibitors
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

What is the purpose of this trial?

This initial cohort of this phase II trial studied the outcomes of using a JAK inhibitor prior to reduced intensity haploidentical (Haplo) transplantation for the treatment of primary or secondary myelofibrosis (MF). The primary risk of using Haplo HCT in patients with MF is graft failure. In the first cohort, all patients engrafted. There were no instances of graft failure. However, a large number of patients did have graft versus host disease as a complication of their transplant. JAK inhibitors have since been approved for the indication of graft versus host disease treatment. And we are also using them for graft versus host disease prevention in a study of MF patients with sibling and unrelated donors. Therefore, we are opening a new cohort of the current study using the JAK inhibitor prior to, during and after Haplo transplant. Our goal is to decrease graft versus host disease in patients receiving a Haplo MF transplant without increasing the risk of graft failure.

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, you must be willing to take a JAK inhibitor for at least 8 weeks before the transplant and continue it for 9-12 months after, as tolerated.

What data supports the effectiveness of the treatment for myelofibrosis?

Research shows that using fludarabine and melphalan as part of a reduced-intensity conditioning regimen for stem cell transplants can effectively control myelofibrosis, although it may lead to higher non-relapse mortality compared to other regimens. Both fludarabine-melphalan and fludarabine-busulfan regimens have been used successfully, with similar overall survival rates.12345

Is the combination of melphalan and fludarabine safe for use in stem cell transplants?

Melphalan and fludarabine are generally used in stem cell transplants, but there have been rare reports of severe heart problems (left ventricular failure) when used together. This suggests that while they are often safe, there is a risk of serious heart issues that should be monitored.46789

How is the stem cell transplant treatment for myelofibrosis using Cyclophosphamide, Fludarabine, and Melphalan different from other treatments?

This treatment is unique because it combines Cyclophosphamide, Fludarabine, and Melphalan as a conditioning regimen for stem cell transplants, which is a curative approach for myelofibrosis. The combination of these drugs is used to prepare the body for the transplant by suppressing the immune system and creating space in the bone marrow for new stem cells, offering a potentially more effective disease control compared to other regimens.2341011

Research Team

RB

Rachel B. Salit

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

This trial is for adults over 18 with primary or secondary myelofibrosis who may benefit from a stem cell transplant. They should have been on a JAK inhibitor for at least 8 weeks, have good organ function, and not be pregnant or HIV positive. Ideal candidates don't have severe liver disease, uncontrolled infections, or previous allogeneic transplants.

Inclusion Criteria

My condition is classified as intermediate-1, intermediate-2, or high-risk.
ABO matched donors preferred over minor ABO mismatched and major ABO mismatch donors
Ability to understand and sign a written informed consent document
See 14 more

Exclusion Criteria

Pregnant or trying to conceive
Platelets < 100 (caution for platelets > 50)
I have a donor who is a perfect or near-perfect match for me.
See 9 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

JAK Inhibitor Therapy

Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation.

8 weeks

Conditioning and Transplant

Patients receive melphalan, fludarabine, and undergo total-body irradiation followed by peripheral blood stem cell infusion.

6 days

GVHD Prophylaxis

Patients receive cyclophosphamide, tacrolimus, mycophenolate mofetil, and G-CSF for GVHD prophylaxis.

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-ups between day 80-100, at 1 year, and then up to 5 years.

Up to 5 years

Treatment Details

Interventions

  • Cyclophosphamide
  • Fludarabine
  • JAK Inhibitor
  • Melphalan
  • Tacrolimus
Trial OverviewThe study tests if taking a JAK inhibitor before undergoing reduced intensity haploidentical transplantation can lower graft failure in myelofibrosis patients. It includes pre-treatment with drugs like Cyclophosphamide and Fludarabine followed by stem cell transplantation.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Cohort II (JAK inhibitor, conditioning, GVHD prophylaxis)Experimental Treatment16 Interventions
JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation. Additionally, patients receive a JAK inhibitor following transplantation beginning day 5 through 9-12 months after transplant. CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0. TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0. GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is \> 1,500/mm\^3. All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.
Group II: Cohort I (JAK inhibitor, conditioning, GVHD prophylaxis)Experimental Treatment16 Interventions
JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation. CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0. TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0. GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is \> 1,500/mm\^3. All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.

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

Find a Clinic Near You

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+

Findings from Research

In a study of 61 patients undergoing allogeneic stem cell transplantation for myelofibrosis, overall survival rates were similar across three reduced intensity conditioning regimens: Busulfan Fludarabine (BuFlu), Fludarabine Bis-chlorethyl-nitroso-urea/carmustine Melphalan (FBM), and Fludarabine Melphalan (FluMel).
Patients receiving FBM or FluMel showed significantly higher rates of 100% donor chimerism at both day +30 and day +100 compared to those receiving BuFlu, indicating better engraftment with these regimens.
Comparison of reduced intensity conditioning regimens used in patients undergoing hematopoietic stem cell transplantation for myelofibrosis.Jain, T., Kunze, KL., Temkit, M., et al.[2021]
In a study of 160 patients with myelofibrosis undergoing reduced-intensity conditioning (RIC) for allogeneic stem cell transplantation, the fludarabine-melphalan (FM) regimen resulted in a higher incidence of acute graft-versus-host disease (62%) compared to the fludarabine-busulfan (FB) regimen (31%).
While both RIC regimens showed similar overall survival rates (52% for FM and 59% for FB), the FM regimen was associated with a significantly lower relapse rate, indicating it may provide better disease control despite a higher risk of nonrelapse mortality.
Outcome after Transplantation According to Reduced-Intensity Conditioning Regimen in Patients Undergoing Transplantation for Myelofibrosis.Robin, M., Porcher, R., Wolschke, C., et al.[2018]
In a study of 872 adults with myelofibrosis undergoing allogeneic hematopoietic cell transplantation (allo-HCT), the conditioning regimen of fludarabine/busulfan was associated with better overall survival and lower rates of early non-relapse mortality and acute graft-versus-host disease (GvHD) compared to fludarabine/melphalan in the reduced-intensity conditioning (RIC) group.
In the myeloablative conditioning (MAC) group, fludarabine/busulfan also showed lower rates of acute GvHD and improved graft-versus-host disease-free relapse-free survival (GRFS) compared to busulfan/cyclophosphamide, indicating it may be the preferred conditioning regimen for patients with myelofibrosis.
Association between the choice of the conditioning regimen and outcomes of allogeneic hematopoietic cell transplantation for myelofibrosis.Murthy, GSG., Kim, S., Estrada-Merly, N., et al.[2023]

References

Comparison of reduced intensity conditioning regimens used in patients undergoing hematopoietic stem cell transplantation for myelofibrosis. [2021]
Outcome after Transplantation According to Reduced-Intensity Conditioning Regimen in Patients Undergoing Transplantation for Myelofibrosis. [2018]
Association between the choice of the conditioning regimen and outcomes of allogeneic hematopoietic cell transplantation for myelofibrosis. [2023]
Fludarabine and melphalan conditioning with tacrolimus as GVHD prophylaxis for allogeneic stem cell transplant recipients is an effective reduced-intensity combination regimen compared to the conventional regimen. [2021]
Are new conditioning regimens for transplants in acute myelogenous leukemia better? [2019]
Current and Novel Alkylators in Multiple Myeloma. [2023]
In vitro and in vivo activity of melflufen (J1)in lymphoma. [2019]
Acute left ventricular failure following melphalan and fludarabine conditioning. [2013]
In vitro and in vivo antitumor activity of a novel alkylating agent, melphalan-flufenamide, against multiple myeloma cells. [2023]
10.United Statespubmed.ncbi.nlm.nih.gov
Transplantation Outcomes of Myelofibrosis with Busulfan and Fludarabine Myeloablative Conditioning. [2023]
Complete Remission of a Refractory Acute Myeloid Leukemia with Myelodysplastic- and Monosomy 7-Related Changes after a Combined Conditioning Regimen of Plerixafor, Cytarabine and Melphalan in a 4-Year-Old Boy: A Case Report and Review of Literature. [2020]