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Study of Stem Cell Transplant vs. Non-Transplant Therapies in High-Risk Myelofibrosis

Study Purpose

The purpose of this research study is to see how effective hematopoietic stem cell transplantation (HCT) is compared to best available non-transplant therapies (BAT) in patients with high risk myelofibrosis. This will be done by asking participants to choose the treatment that they prefer to receive (HCT or BAT) and then comparing the outcomes of the participants in both treatment groups.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Observational
Eligible Ages	18 Years - 70 Years
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

Recruitment Part:

- Documented diagnosis of pre-fibrotic primary myelofibrosis (pre-fibrotic PMF), overt PMF, post-polycythemia MF (PPV-MF) or post-essential thrombocythemia MF (PET-MF) confirmed by bone marrow biopsy.

- Have been tested or have results available for phenotypic driver mutations (JAK2/CALR/MPL) and high molecular risk (HMR) mutations using a broad myeloid malignancies targeted gene panel.

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

- Able to provide informed consent.

- Adequate organ function.

- Donor search initiated or patient is agreeable to donor search.

- Meet the definition/criteria for high-risk myelofibrosis.

Study Arm Allocation:

- Grade of fibrosis on bone marrow biopsy available according to World Health Organization (WHO) criteria.

- Results available for phenotypic driver mutations (JAK2/CALR/MPL) and targeted sequencing results using a broad myeloid malignancy panel with a minimal requirement to include results on High molecular risk (HMR) mutations such as ASXL1/EZH2/IDH1/IDH2/SRSF2/U2AF1/TP53.

- ECOG performance status 0-2.

- Adequate organ function.

- Information on donor search and donor type available.

Exclusion Criteria:

Recruitment Part:

- Blasts in peripheral blood or bone marrow ≥10% - For patients already on ruxolitinib at study entry, and meet the criteria of ruxolitinib failure.

- Previous history of transformation to blast phase or acute myeloid leukemia.

- Received allogeneic stem cell transplant for myeloproliferative neoplasm.

- Presence of an active uncontrolled infection.

- Myocardial infarction in the preceding 3 months.

- Active hepatitis A, B or C.

- Known human immunodeficiency virus (HIV) positive.

- History of active malignancy in the previous 2 years, except basal cell carcinoma or squamous cell carcinoma of skin or stage 0 cervical cancer.

- Any psychiatric illness or social circumstances or significant co-morbid conditions that will prevent patient from proceeding to allogeneic hematopoietic cell transplantation.

- Pregnant or breastfeeding women.

Study Arm Allocation:

- Blasts in peripheral blood or bone marrow ≥10% - Meet the criteria of ruxolitinib failure.

- Presence of an active uncontrolled infection.

- Myocardial infarction in the preceding 3 months.

- Active hepatitis A, B or C.

- Known HIV positive.

- History of active malignancy in the previous 2 years, except basal cell carcinoma or squamous cell carcinoma of skin or stage 0 cervical cancer.

- Pregnant or breastfeeding women.

- Any psychiatric illness or social circumstances or significant co-morbid conditions that will prevent patient from proceeding to allogeneic hematopoietic cell transplantation.

- Time between registration and allocation of study arm >24 weeks

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT04217356
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	University Health Network, Toronto
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Vikas Gupta, M.D.
Principal Investigator Affiliation	Princess Margaret Cancer Centre
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	Canada
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Myelofibrosis, High-Risk Cancer, Bone Marrow Cancer

Additional Details

There is currently little information regarding which treatments are best for patients with myelofibrosis. On one hand, hematopoietic stem cell transplantation (HCT) is potentially curative treatment but is associated with significant risk of complications related to graft failure (the new donor cells does not grow properly after the transplant), side effects such as graft versus host disease (the patient's cells attack the new donor cells), and risk of infections. Non-transplant therapies such as ruxolitinib provide effective symptom control for few months to few years, but are not curative in nature. As such, this study will compare the effectiveness of HCT versus best available non-transplant therapies (BAT) in patients with high risk myelofibrosis. This is an observational study, meaning that participants will be followed to assess the effects of their treatment, but no intervention (treatments) will be given as a part of this study.

Arms & Interventions

Arms

: Hematopoietic stem cell transplant (HCT)

Standard of care hematopoietic stem cell transplant with a matched donor.

: Best available non-transplant therapies (BAT)

Standard of care treatment with a janus kinase (JAK) inhibitor drug called ruxolitinib or treatment with an antimetabolite drug called hydroxyurea.

Interventions

Biological: - Hematopoietic stem cell transplant

Intravenous infusion of hematopoietic stem cells from a donor.

Drug: - Ruxolitinib

Ruxolitinib is type of drug called a janus kinase (JAK) inhibitor. Ruxolitinib is taken orally (by mouth).

Drug: - Hydroxyurea

Hydroxyurea is a type of drug called an antimetabolite. Hydroxyurea is taken orally (by mouth).

Contact a Trial Team

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