Study of Stem Cell Transplant vs. Non-Transplant Therapies in High-Risk Myelofibrosis (ALLO-BAT)

University Health Network, Toronto

Status

Active, not recruiting

Conditions

Myelofibrosis

Bone Marrow Cancer

High-Risk Cancer

Treatments

Biological: Hematopoietic stem cell transplant

Drug: Ruxolitinib

Drug: Hydroxyurea

Study type

Observational

Funder types

Other

Identifiers

NCT04217356

ALLO-BAT (Other Identifier)

19-6362

Details and patient eligibility

About

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.

Full 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.

Enrollment

90 estimated patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

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