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Trial record 1 of 1 for:    M20-178; NCT04468984
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Study of Oral Navitoclax Tablet in Combination With Oral Ruxolitinib Tablet to Assess Change in Spleen Volume in Adult Participants With Relapsed/Refractory Myelofibrosis (TRANSFORM-2)

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ClinicalTrials.gov Identifier: NCT04468984
Recruitment Status : Recruiting
First Posted : July 13, 2020
Last Update Posted : October 27, 2021
Sponsor:
Information provided by (Responsible Party):
AbbVie

Tracking Information
First Submitted Date  ICMJE July 10, 2020
First Posted Date  ICMJE July 13, 2020
Last Update Posted Date October 27, 2021
Actual Study Start Date  ICMJE August 31, 2020
Estimated Primary Completion Date April 8, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 10, 2020)
Percentage of Participants who achieve Spleen Volume Reduction of at least 35% at Week 24 (SVR35W24) [ Time Frame: At Week 24 ]
Reduction in spleen volume is measured by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT), per International Working Group (IWG) criteria.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 26, 2021)
  • Percentage of Participants who achieve at least 50% Reduction in Total Symptom Score (TSS) [ Time Frame: Baseline (Week 0) Up to Week 24 ]
    Reduction in TSS is measured by Myelofibrosis Symptom Assessment Form (MFSAF) v4.0.
  • Percentage of Participants who achieve Spleen Volume Reduction of at least 35% (SVR35) [ Time Frame: Baseline (Week 0) Up to Week 97 ]
    Reduction in spleen volume is measured by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT), per International Working Group (IWG) criteria.
  • Duration of SVR35 [ Time Frame: Baseline (Week 0) Up to Week 97 ]
    Duration of SVR35 is defined as the time between the date of first response of spleen volume reduction of 35% achievement to the date of disease progression, or to the date of death, whichever occurs first.
  • Change in Fatigue [ Time Frame: Baseline (Week 0) Up to Week 24 ]
    Change in fatigue will be assessed using the Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form (SF) 7a.
  • Time to Deterioration of Physical Functioning [ Time Frame: Baseline (Week 0) Up to Week 97 ]
    Time to deterioration of physical functioning is measured by the physical functioning domain of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30, or death.
  • Proportion of Participants who achieved Anemia Response [ Time Frame: Baseline (Week 0) Up to Week 97 ]
    The rate of anemia response will be assessed according to current International Working Group-Myeloproliferative Neoplasms Research and European LeukemiaNet (IWG-MRT/ELN) criteria.
  • Overall Survival [ Time Frame: Up to approximately 3 years ]
    Overall survival is defined as the time from start of study to the date of death from any cause.
  • Leukemia-Free Survival [ Time Frame: Up to approximately 3 years ]
    Leukemia free survival is the time from start of study to the date of development of leukemia.
  • Overall Response of Clinical Improvement [ Time Frame: Baseline (Week 0) Up to Week 97 ]
    Clinical improvement is defined as the achievement of anemia, spleen or symptoms response without progressive disease, per International Working Group (IWG) criteria.
  • Percentage of Participants who achieve Reduction in Grade of Bone Marrow Fibrosis [ Time Frame: Baseline (Week 0) Up to Week 97 ]
    Change in grade of bone marrow fibrosis will be measured per the European consensus grading system through bone marrow biopsy.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 10, 2020)
  • Percentage of Participants who achieve at least 50% Reduction in Total Symptom Score (TSS) [ Time Frame: Baseline (Week 0) Up to Week 24 ]
    Reduction in TSS is measured by Myelofibrosis Symptom Assessment Form (MFSAF) v4.0.
  • Percentage of Participants who achieve Spleen Volume Reduction of at least 35% (SVR35) [ Time Frame: Baseline (Week 0) Up to Week 96 ]
    Reduction in spleen volume is measured by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT), per International Working Group (IWG) criteria.
  • Duration of SVR35 [ Time Frame: Baseline (Week 0) Up to Week 96 ]
    Duration of SVR35 is defined as the time between the date of first response of spleen volume reduction of 35% achievement to the date of disease progression, or to the date of death, whichever occurs first.
  • Change in Fatigue [ Time Frame: Baseline (Week 0) Up to Week 96 ]
    Change in fatigue will be assessed using the Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form (SF) 7a.
  • Time to Deterioration of Physical Functioning [ Time Frame: Baseline (Week 0) Up to Week 96 ]
    Time to deterioration of physical functioning is measured by the physical functioning domain of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-30.
  • Proportion of Participants who achieved Anemia Response [ Time Frame: Baseline (Week 0) Up to Week 96 ]
    The rate of anemia response will be assessed according to current International Working Group-Myeloproliferative Neoplasms Research and European LeukemiaNet (IWG-MRT/ELN) criteria.
  • Overall Survival [ Time Frame: Up to approximately 3 years ]
    Overall survival is defined as the time from start of study to the date of death from any cause.
  • Leukemia-Free Survival [ Time Frame: Up to approximately 3 years ]
    Leukemia free survival is the time from start of study to the date of development of leukemia.
  • Overall Response Rate (ORR) [ Time Frame: Baseline (Week 0) Up to Week 96 ]
    ORR is defined as percentage of participants with documented response of partial response (PR) or better, according to the International Working Group (IWG) criteria.
  • Composite Response Rate [ Time Frame: Baseline (Week 0) Up to Week 96 ]
    Achievement of anemia, spleen or symptoms response without progressive disease, per International Working Group (IWG) criteria.
  • Percentage of Participants who achieve Reduction in Grade of Bone Marrow Fibrosis [ Time Frame: Baseline (Week 0) Up to Week 96 ]
    Change in grade of bone marrow fibrosis will be measured per the European consensus grading system through bone marrow biopsy.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Oral Navitoclax Tablet in Combination With Oral Ruxolitinib Tablet to Assess Change in Spleen Volume in Adult Participants With Relapsed/Refractory Myelofibrosis
Official Title  ICMJE A Randomized, Open-Label, Phase 3 Study Evaluating Efficacy and Safety of Navitoclax in Combination With Ruxolitinib Versus Best Available Therapy in Subjects With Relapsed/Refractory Myelofibrosis (TRANSFORM-2)
Brief Summary

Myelofibrosis (MF) is a bone marrow illness that affects blood-forming tissues in the body. MF disturbs the body's normal production of blood cells, causing extensive scarring in the bone marrow. This leads to severe anemia, weakness, fatigue, and an enlarged spleen. The purpose of this study is to assess safety and change in spleen volume when navitoclax is given in combination with ruxolitinib, as compared to best available therapy, for adult participants with MF.

Navitoclax is an investigational drug (not yet approved) being developed for the treatment of MF. The study has 2 arms - A and B. In Arm A, participants will receive navitoclax in combination with ruxolitinib. In Arm B, participants will receive the best available therapy (BAT) for MF. Adult participants with a diagnosis of relapsed/refractory (R/R) MF will be enrolled. Approximately 330 participants will be enrolled in approximately 210 sites across the world.

In Arm A, participants will receive oral navitoclax tablet once daily with oral ruxolitinib tablet twice daily. In Arm B, participants will receive the BAT as identified by the investigator. Treatment will continue until clinical benefit is not seen, participants cannot tolerate the study drugs, or participants withdraw consent. The approximate treatment duration is about 3 years.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of treatment will be checked by medical assessments, blood and bone marrow tests, checking for side effects, and completing questionnaires.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Myelofibrosis (MF)
Intervention  ICMJE
  • Drug: Navitoclax
    Tablet; Oral
    Other Name: ABT-263
  • Drug: Ruxolitinib
    Tablet; Oral
  • Drug: Best Available Therapy (BAT)
    Tablet/Capsule; Oral or Solution for Subcutaneous Injection
Study Arms  ICMJE
  • Experimental: Arm A: Navitoclax + Ruxolitinib
    Participants will receive navitoclax tablets once daily and ruxolitinib tablets twice daily.
    Interventions:
    • Drug: Navitoclax
    • Drug: Ruxolitinib
  • Active Comparator: Arm B: Best Available Therapy (BAT)
    Participants will receive one of the BAT options, per the investigator's discretion.
    Intervention: Drug: Best Available Therapy (BAT)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 10, 2020)
330
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 25, 2029
Estimated Primary Completion Date April 8, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Inclusion Criteria:

  • Must be able to complete the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 on at least 4 out of 7 days prior to randomization.

    -- Has at least 2 symptoms with a score >= 3 or a total score of >= 12, as measured by the MFSAF v4.0.

  • Documented diagnosis of primary myelofibrosis (MF) as defined by the World Health Organization (WHO) classification, post polycythemia vera (PPV)-MF, or post essential thrombocytopenia (PET)-MF .
  • Classified as intermediate-2 or high-risk MF, as defined by the Dynamic International Prognostic Scoring System Plus (DIPSS+).
  • Must currently be on treatment or have received prior treatment with a single Janus Kinase 2 (JAK2) inhibitor, ruxolitinib, and meet one of the following criteria (in addition to the minimum splenomegaly and symptom burden also required for eligibility):

    • Treatment with ruxolitinib for >= 24 weeks that was stopped due to lack of spleen response (refractory), or loss of spleen response or symptom control after a previous response (relapsed), or was continued despite relapsed/refractory status.
    • Treatment with ruxolitinib for < 24 weeks with documented disease progression while on therapy as defined by any of the following:

      • Appearance of new splenomegaly that is palpable to at least 5 cm below the left costal margin (LCM) in participants with no evidence of splenomegaly prior to the initiation of ruxolitinib.
      • A >= 100% increase in the palpable distance below the LCM in participants with measurable spleen distance 5 to 10 centimeters (cm) prior to the initiation of ruxolitinib.
      • A >= 50% increase in the palpable distance below the LCM in participants with measurable spleen distance > 10 cm prior to the initiation of ruxolitinib.
      • A spleen volume increase of >= 25% (as assessed by Magnetic Resonance Imaging [MRI] or Computed Tomography [CT] scan) in participants with a spleen volume assessment prior to the initiation of ruxolitinib.
  • Prior or current treatment with ruxolitinib for >= 28 days with intolerance defined as new RBC transfusion requirement (at least 2 units/month for 2 months) while receiving a total daily ruxolitinib dose of >= 30 mg but unable to reduce dose further due to lack of efficacy.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
  • Splenomegaly defined as palpable spleen measurement >= 5 cm below left costal margin or spleen volume >= 450 cm3 as assessed centrally by MRI or CT scan.
  • Baseline platelet count >= 100 × 10^9/L.

Exclusion Criteria:

  • Received prior treatment with a BH3-mimetic compound, bromodomain and extra-terminal (BET) inhibitor, or prior use of > 1 JAK2 inhibitor or stem cell transplant.
  • Eligible for allogeneic stem cell transplantation at the time of study entry.
  • Receiving medication that interferes with coagulation or platelet function within 3 days prior to the first dose of study drug or during the study treatment period except for low dose aspirin (up to 100 mg daily) and low molecular weight heparin (LMWH).
  • Receiving anticancer therapy for an active malignancy or MF including chemotherapy, radiation therapy, hormonal therapy within 30 days prior to first dose of study drug, and during the study treatment period (other than any overlapping therapy as part of the selected BAT).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: ABBVIE CALL CENTER 844-663-3742 abbvieclinicaltrials@abbvie.com
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   Bulgaria,   Canada,   Croatia,   Czechia,   Denmark,   France,   Germany,   Greece,   Hungary,   Israel,   Italy,   Japan,   Korea, Republic of,   New Zealand,   Poland,   Puerto Rico,   Russian Federation,   Serbia,   South Africa,   Spain,   Sweden,   Switzerland,   Taiwan,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04468984
Other Study ID Numbers  ICMJE M20-178
2020-000557-27 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
URL: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html
Responsible Party AbbVie
Study Sponsor  ICMJE AbbVie
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: ABBVIE INC. AbbVie
PRS Account AbbVie
Verification Date October 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP