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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04217356
Recruitment Status : Not yet recruiting
First Posted : January 3, 2020
Last Update Posted : January 3, 2020
Sponsor:
Information provided by (Responsible Party):
University Health Network, Toronto

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.

Condition or disease Intervention/treatment
Myelofibrosis High-Risk Cancer Biological: Hematopoietic stem cell transplant Drug: Ruxolitinib Drug: Hydroxyurea

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.

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Study Type : Observational
Estimated Enrollment : 90 participants
Observational Model: Cohort
Time Perspective: Prospective
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)
Estimated Study Start Date : February 10, 2020
Estimated Primary Completion Date : February 10, 2025
Estimated Study Completion Date : August 10, 2025


Group/Cohort Intervention/treatment
Hematopoietic stem cell transplant (HCT)
Standard of care hematopoietic stem cell transplant with a matched donor.
Biological: Hematopoietic stem cell transplant
Intravenous infusion of hematopoietic stem cells from a 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.
Drug: Ruxolitinib
Ruxolitinib is type of drug called a janus kinase (JAK) inhibitor. Ruxolitinib is taken orally (by mouth).
Other Name: JAKAVI

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




Primary Outcome Measures :
  1. Number of patients allocated to hematopoietic stem cell transplantation (HCT) [ Time Frame: 5 years ]
  2. Number of patients allocated to best available non-transplant therapies (BAT) [ Time Frame: 5 years ]
  3. Overall survival rate of patients who receive hematopoietic stem cell transplantation (HCT) [ Time Frame: 5 years ]
    Time from study allocation to death or last follow up.

  4. Overall survival rate of patients who receive best available non-transplant therapies (BAT) [ Time Frame: 5 years ]
    Time from study allocation to death or last follow up.


Secondary Outcome Measures :
  1. Median change in Patient Global Impression of Change (PGIC) score [ Time Frame: 0 and 36 months ]
    Range from -3 to 3. Positive number equals increase in quality of life.

  2. Median change in MPN Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) [ Time Frame: 0 and 36 months ]
    Range from 0 to 10. Increase equals worsening of symptoms.

  3. Median change in FACT-BMT Questionnaire [ Time Frame: 0 and 36 months ]
    Range from 1 to 4. Increase equals increase in quality of life.

  4. Disease-free survival of patients who receive hematopoietic stem cell transplantation (HCT) [ Time Frame: 5 years ]
    Time from allocation to study arm to death/acute myeloid leukemia transformation or last follow up.

  5. Disease-free survival of patients who receive best available non-transplant therapies (BAT) [ Time Frame: 5 years ]
    Time from allocation to study arm to death/acute myeloid leukemia transformation or last follow up.

  6. Number of patients who receive hematopoietic stem cell transplantation (HCT) in remission (complete and partial) [ Time Frame: 3 years ]
  7. Number of patients who receive best available non-transplant therapies (BAT) in remission (complete and partial) [ Time Frame: 3 years ]

Biospecimen Retention:   Samples With DNA
Blood samples for future research related to hematological (blood) cancers and their treatments.


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04217356


Contacts
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Contact: Vikas Gupta, M.D. 416-946-2885 vikas.gupta@uhn.ca

Locations
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Canada, Alberta
Foothills Medical Centre
Calgary, Alberta, Canada, T2N2T9
Contact: Sonia Cerquozzi, M.D.    403-944-5948      
Principal Investigator: Sonia Cerquozzi, M.D.         
Cross Cancer Institute
Edmonton, Alberta, Canada, T6G2G3
Contact: Elena Liew, M.D.    780-417-1584      
Principal Investigator: Elena Liew, M.D.         
Canada, British Columbia
St. Paul's Hospital
Vancouver, British Columbia, Canada, V6E1M7
Contact: Lynda Foltz, M.D.    604-682-2344 ext 64986      
Principal Investigator: Lynda Foltz, M.D.         
Canada, Nova Scotia
Nova Scotia Health Authority
Halifax, Nova Scotia, Canada, B3H2Y9
Contact: Mahmoud Elsawy, M.D.    902-473-7006      
Principal Investigator: Mahmoud Elsawy, M.D.         
Canada, Ontario
Princess Margaret Cancer Centre
Toronto, Ontario, Canada, M5G2M9
Contact: Vikas Gupta, M.D.    416-946-2885      
Principal Investigator: Vikas Gupta, M.D.         
Sponsors and Collaborators
University Health Network, Toronto
Investigators
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Principal Investigator: Vikas Gupta, M.D. Princess Margaret Cancer Centre
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Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT04217356    
Other Study ID Numbers: 19-6362
ALLO-BAT ( Other Identifier: Princess Margaret Cancer Centre )
First Posted: January 3, 2020    Key Record Dates
Last Update Posted: January 3, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Primary Myelofibrosis
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Hydroxyurea
Antineoplastic Agents
Antisickling Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors