Chemo/Radiation Therapy + Stem Cell Transplant for Myelofibrosis

Not currently recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Disqualifiers: HIV, Hepatitis B/C, Liver cirrhosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of chemotherapy, radiation, and donor stem cell transplants to treat secondary myelofibrosis, a condition where scar tissue forms in the bone marrow and affects blood cell production. The goal is to determine the safety and effectiveness of this treatment in stopping cancer cells and helping the bone marrow produce healthy blood cells again. Participants with myelofibrosis that hasn't responded to other treatments and who seek a donor stem cell transplant might be a good fit. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this novel therapy.

Do I have to stop taking my current medications for the trial?

The trial requires that if you are taking a JAK2 inhibitor, you must stop it 1-2 days before starting the treatment regimen. For other medications, the protocol does not specify, so it's best to discuss with the trial team.

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

Research has shown that using healthy blood-forming cells from a donor, known as allogeneic stem cell transplantation, can be a safe and effective treatment for myelofibrosis. Studies have found good survival rates, especially in younger patients and women.

Cyclophosphamide, a drug used in some chemotherapy treatments, has proven safe for myelofibrosis patients. A study with 14 patients using lower doses of cyclophosphamide reported positive results.

Fludarabine, another chemotherapy drug, is often used in combination with other treatments. While some patients experience their disease worsening or returning, others do not, indicating mixed results regarding its safety.

Melphalan is used in high doses to prepare patients for transplants and has been reported as safe. However, it must be administered carefully to avoid complications.

Tacrolimus, which helps prevent the body from rejecting the transplant, is generally considered safe. Studies have shown it can effectively prevent graft-versus-host disease, where donor cells attack the patient's body.

Total-body irradiation is part of the treatment plan. Increasing the dose has been shown to lower the chances of relapse and rejection.

Since this trial is in an early phase, safety is still being closely monitored. Participants may experience side effects, but early studies suggest these treatments can be well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for myelofibrosis because it combines the power of chemotherapy, radiation, and stem cell transplant in a unique way. Unlike standard treatments that might focus solely on symptom management or single-modality approaches, this regimen uses a combination of potent chemotherapy drugs like Cyclophosphamide, Fludarabine, and Melphalan, alongside Total-Body Irradiation and Allogeneic Hematopoietic Stem Cell Transplantation. This approach could potentially offer a more comprehensive attack on the disease by replacing the patient's faulty blood cells with healthy donor cells. Additionally, the use of Tacrolimus helps to manage the immune response, reducing the risk of rejection and graft-versus-host disease, which is a significant concern in stem cell transplants. Researchers hope this multi-faceted strategy will improve outcomes and offer new hope for those battling this challenging condition.

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

Research has shown that allogeneic hematopoietic stem cell transplantation (allo-HCT) can potentially cure myelofibrosis, with success rates ranging from 30% to 65%. In this trial, participants receive a combination of treatments, including Cyclophosphamide, which helps the new cells take hold and improve outcomes after the transplant. Fludarabine, when combined with other medications, has effectively controlled the disease and increased survival rates. Melphalan has led to positive responses, with many patients experiencing a return to normal symptoms. Tacrolimus prevents complications after the transplant and has improved survival rates. Total-body irradiation, part of this trial's treatment, kills cancer cells and prepares the body for new healthy cells. This combination of treatments aims to stop cancer growth and encourage the production of healthy blood cells. ^{1 2 4 6 7}

Who Is on the Research Team?

Monzr M. Al Malki

Principal Investigator

City of Hope Medical Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with secondary myelofibrosis who are fit (Karnofsky performance >=70%), have adequate organ function, and no severe pulmonary or liver conditions. Donors must be a genetic half-match without certain infections or health risks, and not pregnant if female of childbearing potential.

Inclusion Criteria

DONOR: Is approved and completed evaluation prior to recipient initiation of the preparative regimen per institutional guidelines

Left ventricular ejection fraction (LVEF) >= 50%

My donor is a relative who is not my mother and matches half of my HLA markers.

Exclusion Criteria

I have severe liver issues with symptoms like bleeding, fluid buildup, or confusion.

I have had a transplant involving solid organ, stem cell, bone marrow, or blood.

I have liver cirrhosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy and Radiation

Participants receive melphalan and fludarabine chemotherapy, followed by total body irradiation before hematopoietic cell transplantation

7 days

Daily visits for chemotherapy and radiation administration

Hematopoietic Cell Transplantation

Participants undergo hematopoietic cell transplantation and receive post-transplant cyclophosphamide

5 days

Daily visits for transplantation and post-transplant medication

Post-Transplant Treatment

Participants receive tacrolimus, mycophenolate mofetil, and G-CSF to support recovery and prevent complications

6 months

Regular visits for medication administration and monitoring

Follow-up

Participants are monitored for safety, effectiveness, and long-term outcomes after treatment

Up to 2 years

Periodic visits for follow-up assessments

What Are the Treatments Tested in This Trial?

Interventions

• Allogeneic Hematopoietic Stem Cell Transplantation
• Cyclophosphamide
• Fludarabine
• Melphalan
• Mycophenolate Mofetil
• Tacrolimus
• Total-Body Irradiation

Trial Overview The trial tests a treatment combining chemotherapy drugs (Melphalan, Mycophenolate Mofetil, Tacrolimus, Cyclophosphamide, Fludarabine), total body irradiation, and donor blood stem cell transplant to see how well it treats secondary myelofibrosis.

How Is the Trial Designed?

Group I: Treatment (combination chemotherapy, TBI, HCT) Experimental Treatment 9 Interventions

Patients receive melphalan IV over 30 minutes on day -5, fludarabine IV over 30-60 minutes on days -5 to -2. Patients undergo TBI on day -1 and HCT on day 0. Patients receive cyclophosphamide IV over 1-2 hours on days 3 and 4. Starting on day 5, patients receive tacrolimus IV then PO for 6 months followed by a taper, mycophenolate mofetil PO TID until day 35, and G-CSF IV daily until absolute neutrophil count \> 1,500/mm\^3 for 3 consecutive days. Treatment continues in the absence of disease progression or unexpected toxicity.

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?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6717573/

Long-term outcome after allogeneic hematopoietic cell ... Only allogeneic hematopoietic stem cell transplantation (HSCT) has been proposed as curative; overall, HSCT has been reported to cure 30-65% of these patients.

2. sciencedirect.com sciencedirect.com/science/article/pii/S266663672400558X

Adult Allogeneic Hematopoietic Cell Transplantation for ... The 3-year overall survival was 55% (95% CI, 44%-65%; Figure 2). The 1-year cumulative incidence of relapse was 7% (95% CI, 3%-13%) and the 1-year cumulative ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34052505/

Outcomes of Allogeneic Hematopoietic Cell Transplantation in ... Allogeneic hematopoietic cell transplant (allo-HCT) remains the only potentially curative therapeutic modality for patients with primary or secondary ...

4. astctjournal.org astctjournal.org/article/S1083-8791(17)30454-8/fulltext

Allogeneic Stem Cell Transplantation in Myelofibrosis Two-year overall survival and event-free survival rates were 44% and 30%, respectively, despite a concern for graft failure. Conditioning regimens. Patient ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/ajh.27660

Allogeneic Stem Cell Transplant for Myelofibrosis and ... Long-term outcomes, including OS, progression-free survival (PFS), NRM, and relapse rates, show progressive improvement, probably attributed to ...

6. astctjournal.org astctjournal.org/article/S1083-8791(19)30144-2/fulltext

Comparison of Outcomes of Allogeneic Transplantation for ... We conducted this retrospective study using the Japanese national registry data for 224 PMF patients to compare the outcomes of first allogeneic HSCT from HLA- ...

7. ashpublications.org ashpublications.org/bloodadvances/article/8/16/4281/516713/Donor-types-and-outcomes-of-transplantation-in

Donor types and outcomes of transplantation in myelofibrosis We evaluate the impact of donor types on outcomes of hematopoietic cell transplantation (HCT) in myelofibrosis, using the Center for International Blood and ...