Clinical trial NCT04217356: Study of Stem Cell Transplant vs. Non-Transplant Therapies in High-Risk Myelofibrosis
Official title: A Patient Preferences-Controlled Study of Allogeneic Hematopoietic Cell Transplantation Versus Best Available Non-Transplant Therapies in Patients With High-Risk Myelofibrosis (ALLO-BAT Study)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Myelofibrosis
High-Risk Cancer
Bone Marrow Cancer
Keywords: High-Risk Myelofibrosis
Stem Cell
Transplantation
Myelofibrosis
Bone marrow cancer
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2020-01-03
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with high-risk myelofibrosis including pre-fibrotic primary myelofibrosis (pre-fibrotic primary myelofibrosis), overt primary myelofibrosis, post-polycythemia myelofibrosis or post-essential thrombocythemia myelofibrosis.

Brief summary: 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.

Detailed description: 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.

Eligibility 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

Primary outcomes:
measure: Number of patients allocated to hematopoietic stem cell transplantation (HCT)
timeFrame: 5 years
measure: Number of patients allocated to best available non-transplant therapies (BAT)
timeFrame: 5 years
measure: Overall survival rate of patients who receive hematopoietic stem cell transplantation (HCT)
timeFrame: 5 years
measure: Overall survival rate of patients who receive best available non-transplant therapies (BAT)
timeFrame: 5 years
Secondary outcomes:
measure: Median change in Patient Global Impression of Change (PGIC) score
timeFrame: 0 and 36 months
measure: Median change in MPN Symptom Assessment Form Total Symptom Score (MPN-SAF TSS)
timeFrame: 0 and 36 months
measure: Median change in FACT-BMT Questionnaire
timeFrame: 0 and 36 months
measure: Disease-free survival of patients who receive hematopoietic stem cell transplantation (HCT)
timeFrame: 5 years
measure: Disease-free survival of patients who receive best available non-transplant therapies (BAT)
timeFrame: 5 years
measure: Number of patients who receive hematopoietic stem cell transplantation (HCT) in remission (complete and partial)
timeFrame: 3 years
measure: Number of patients who receive best available non-transplant therapies (BAT) in remission (complete and partial)
timeFrame: 3 years
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Halifax
country: Canada
facility: Nova Scotia Health Authority
state: Nova Scotia
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
Study officials:
affiliation: Princess Margaret Cancer Centre
name: Vikas Gupta, M.D.
role: PRINCIPAL_INVESTIGATOR
References: