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Phase 2 N=27 Randomized Quadruple-blind Treatment

A Phase 2 Study of RO7490677 In Participants With Myelofibrosis

Primary Myelofibrosis · Polycythemia Vera · Post-Essential Thrombocythemia Myelofibrosis

Enrolled (actual)
27
Serious AEs
38.4%
Results posted
Jan 2022
Primary outcome: Primary: Stage 1 Main Phase: Overall Response Rate (ORR) — 37.5; 14.3; 33.3; 50.0 Percentage of Participants

Study Design & Population

Study type
Interventional
Phase
Phase 2
Interventions
RO7490677 (Biological); Ruxolitinib (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Hoffmann-La Roche
Primary completion
Jul 2020

Outcome Measures

OutcomeResultp-value
PRIMARY
Stage 1 Main Phase: Overall Response Rate (ORR)
37.5; 14.3; 33.3; 50.0
PRIMARY
Stage 2 Main Phase: Bone Marrow Response Rate (BMRR)
30.3; 31.3; 25.0
PRIMARY
Stage 1 Main + Open-Label Extension (OLE): ORR
50.0; 71.4; 50.0; 66.7
PRIMARY
Stage 2 Main + Open-Label Extension (OLE): BMRR
30.3; 34.4; 25.0
SECONDARY
Stage 1 Main Phase: BMRR
37.5; 14.3; 16.7; 50.0
SECONDARY
Stage 1 Main Phase: Modified Myeloproliferative Neoplasms Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) Changes
23.1; 16.9; 26.8; 15.3; -5.3; 5.7
SECONDARY
Stage 2 Main Phase: BMRR
30.3; 31.3; 25.0
SECONDARY
Stage 2 Main Phase: BMRR - Reduction of Bone Marrow Fibrosis by Visit
10.7; 24.0; 19.2; 23.8; 11.8; 10.5
SECONDARY
Stage 2 Main Phase: Duration of Bone Marrow Improvement
NA; 12.0; 12.1
SECONDARY
Stage 2 Main Phase: Hemoglobin Improvement
15.2; 15.6; 6.3
SECONDARY
Stage 2 Main Phase: Platelet Improvement
27.3; 34.4; 37.5
SECONDARY
Stage 2 Main Phase: Symptom Improvement
5; 2; 1; 6; 3; 2
SECONDARY
Stage 2 Main Phase: Percentage of Participants With Complete Response (CR), Partial Response (PR), Clinical Improvement (CI), Stable Disease (SD), and Progressive Disease (PD) According to IWG-MRT Criteria
0; 0; 0; 0; 0; 0

Summary

RO7490677 is an investigational drug that is being developed for possible use in the treatment of myelofibrosis (MF), a disease in which the bone marrow, which is the organ in the body that makes blood cells, is replaced by fibrosis, or excess scar tissue. The purpose of this study is to gather information on whether RO7490677 has an effect on the MF disease, whether it is safe in patients with MF, and how well it is tolerated.

Eligibility Criteria

Inclusion Criteria

  • Participants must be ≥18 years of age at the time of signing the Informed Consent Form (ICF);
  • Participants must voluntarily sign an ICF;
  • Participants must have a pathologically confirmed diagnosis of PMF as per the WHO diagnostic criteria or post ET/PV MF;
  • At least Grade 2 marrow fibrosis according to the WHO Grading of Bone Marrow Fibrosis;
  • Intermediate-1, intermediate -2, or high risk disease according to the IWG -MRT Dynamic International Prognostic Scoring System
  • A bone marrow biopsy must be performed within four weeks prior to Cycle 1 Day 1 treatment to establish the baseline fibrosis score;
  • Participants must not be candidates for ruxolitinib based on EITHER:
  • Platelet count 55 years, must have a negative serum pregnancy test within four weeks prior to the first dose of study drug and must agree to use adequate methods of birth control throughout the study. Adequate methods of contraception are outlined in the protocol.
  • Ability to adhere to the study visit schedule and all protocol requirements;
  • Must have adequate organ function as demonstrated by the following:
  • ALT (SGPT) and/or AST (SGOT) ≤ 3x upper limit of normal (ULN), or ≤ 4 x ULN (if upon judgment of the treating physician, it is believed to be due to extramedullary hematopoiesis [EMH] related to MF);
  • Direct bilirubin ≤ 1.5 x ULN; or ≤ 2x ULN (if upon judgment of the treating physician, it is believed to be due to EMH related to MF);
  • Serum creatinine ≤ 2.5 mg/dL x ULN.

Exclusion Criteria

  • White blood cell count > 25 x 10e9/L or > 10% peripheral blood blasts;
  • Other invasive malignancies within the last 3 years, except non- melanoma skin cancer and localized cured prostate and cervical cancer;
  • History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months;
  • Presence of active serious infection;
  • Any serious, unstable medical or psychiatric condition that would prevent, (as judged by the Investigator) the participant from signing the informed consent form or any condition, including the presence of laboratory abnormalities, which places the participant at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study;
  • Known history of human immunodeficiency virus (HIV), or known active hepatitis A, B, or C infection;
  • Organ transplant recipients other than bone marrow transplant;
  • Women who are pregnant or lactating.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01981850). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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