AzTrials
AzTrials

Primary MyelofibrosisPhase 1NCT03895112

MPN-RC 118 AVID200 in Myelofibrosis

A Phase 1 study testing AVID200 in people with Primary Myelofibrosis and Post-essential Thrombocythemia Myelofibrosis, run by John Mascarenhas at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Increased levels of TGF-β1 were detected in serum, plasma and BM and positively correlated with both grade of BMF and extent of leukemic cell infiltration in the marrow. TGF-β likely plays a dual role in promoting myelofibrosis and myeloproliferation, both of which are the bone marrow morphologic hallmark of MF. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
AVID200
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
1 siteUnited States
Study dates
15 Feb 2019to 16 May 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subjects must be ≥18 years of age at the time of signing the Informed Consent Form (ICF)
  • Subjects must voluntarily sign an ICF
  • Subjects must have a pathologically confirmed diagnosis of PMF as per the WHO diagnostic criteria or post ET/PV MF (note that all diagnoses must include the presence of at least Grade 2 marrow fibrosis according to the European Consensus on Grading of Bone Marrow Fibrosis (see Table 6) with intermediate -2 or high risk disease according to the IWG-MRT Dynamic International Prognostic Scoring System (DIPSS) (see Table 7)
  • A bone marrow biopsy must be performed within the 30 day screening period, however, a bone marrow biopsy obtained within 90 days of screening without intervening treatments and approved by the study chair may suffice.
  • Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
  • Life expectancy of at least six months
Show all 21Show fewer
  • At least two weeks must have elapsed between the last dose of any MF-directed drug treatments (including investigational therapies and excluding hydroxyurea) and study enrollment
  • Not eligible for ruxolitinib therapy due to a platelet count <50 x 109/L, previously treated and lack/loss of response as defined by at least one of the following:
  • Treatment for ≥3 months with inadequate efficacy response defined as <10% spleen volume reduction by MRI or <30% decrease from baseline in spleen length by physical examination or regrowth to these parameters following an initial response; and/or
  • Treatment for ≥28 days complicated by either
  • Development of a red blood cell transfusion requirement (at least 2 units/month for 2 months) ii. National Cancer Institute (NCI) CTCAE grade ≥ 3 AEs of thrombocytopenia, anemia, hematoma, and/or hemorrhage while being treated with a dosage of < 20 mg BID
  • Recovery to ≤ Grade 1 or baseline of any toxicities due to prior systemic treatments, excluding alopecia
  • Women of child bearing potential (WCBP), defined as a sexually mature woman not surgically sterilized or not post-menopausal for at least 24 consecutive months if ≤55 years or 12 months if >55 years, must have a negative serum pregnancy test at screening and cycle 1 day 1 and must agree to use adequate methods of birth control throughout the study. Adequate methods of contraception include use of oral contraceptives or Depo-Provera, with an additional barrier method (diaphragm with spermicidal gel or condoms with spermicide), double-barrier methods (diaphragm with spermicidal gel and condoms with spermicide), partner vasectomy, and total abstinence.
  • Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
  • 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 extra-medullary hematopoiesis related to MF or documented Gilbert's syndrome);
  • Serum creatinine ≤ 2.0 mg/dL;
  • Platelet count ≥25 x 109/L
  • Ability to adhere to the study visit schedule and all protocol requirements
  • Ability to understand and the willingness to sign a written informed consent

Who cannot join

  • Other invasive malignancies within the last 3 years, except non-melanoma skin cancer and localized cured prostate and cervical cancer.
  • Previous exposure to galunisertib, fresolimumab, sotatercept, or luspatercept.
  • History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months
  • Have moderate or severe cardiovascular disease:
  • have the presence of cardiac disease, including a myocardial infarction within 6 months prior to study entry, unstable angina pectoris, New York Heart Association Class III/IV congestive heart failure, or uncontrolled hypertension
  • have documented major ECG abnormalities (not responding to medical treatments)
Show all 12Show fewer
  • Have predisposing conditions that are consistent with development of aneurysms of the ascending aorta or aortic stress (for example, family history of aneurysms, Marfan-Syndrome, bicuspid aortic valve, evidence of damage to the large vessels of the heart documented by CT scan/MRI with contrast)
  • Presence of active serious infection;
  • Any serious, unstable medical or psychiatric condition that would prevent, (as judged by the Investigator) the subject from signing the informed consent form or any condition, including the presence of laboratory abnormalities, which places the subject 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Icahn School of Medicine at Mount Sinai

    New York, New York, 10029

Other trials in United States

About this study

Official title: Phase I Study of AVID200 in Patients With Myelofibrosis (Myeloproliferative Neoplasms Research Consortium [MPN-RC] 118)

Increased levels of TGF-β1 were detected in serum, plasma and BM and positively correlated with both grade of BMF and extent of leukemic cell infiltration in the marrow. TGF-β likely plays a dual role in promoting myelofibrosis and myeloproliferation, both of which are the bone marrow morphologic hallmark of MF. AVID200 is a drug that targets TGF-β1 and TGF-β3. The study team hypothesizes that inhibiting the TGF-β signaling pathway in MF will decrease the fibrogenic stimuli leading to myelofibrosis and concomitantly interrupt myeloproliferation and restore normal hematopoiesis.

This is a first in human, open-label, multicenter, Phase I/Ib trial of AVID200. Patients must have intermediate-2 or higher primary myelofibrosis (PMF), post-essential thrombocythemia or polycythemia-vera related MF (Post ET/PV MF). This study will enroll up to 24 patients. AVID200 is delivered by IV infusion on day 1 of each 3 week cycle.

Read the detailed description

This is a first in human, open-label, multicenter, Phase I/Ib trial of AVID200. To date, there is no therapy for MF evaluated in the clinic that clearly demonstrates the ability to target the malignant HSC and result in effective and reproducible bone marrow morphologic, cytogenetic and molecular responses. Medicinal therapies that result in disease course modification are urgently needed in this chronic and progressive myeloid malignancy. TGF-β likely plays a dual role in promoting myelofibrosis and myeloproliferation, both of which are the bone marrow morphologic hallmark of MF. The study team proposes that inhibiting the TGF-β signaling pathway in MF will decrease the fibrogenic stimuli leading to myelofibrosis and concomitantly interrupt myeloproliferation and restore normal hematopoiesis. AVID200 is a fusion protein containing TGF-β receptor ectodomains fused to a human Fc IgG domain. AVID200 is a potent TGFβ trap with antibody-like properties which has pM potency against two of the three TGFβ ligands, TGFβ1 and β3.

Being tested
AVID200
Keywords
Therapeutic, Fibrosis, Splenomegaly, Myeloproliferative neoplasms research consortium, Intravenous Infusion, Phase 1
Medical subject headings
Primary Myelofibrosis, Fibrosis, Splenomegaly

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AVID200Drug

    dose cohorts of 21-day cycles

Study groups in NCT03895112
Study groupRoleWhat they receive
AVID200Experimentalintravenous in dose cohorts of 70mg/m2 or 180 mg/m2
Receives: Drug: AVID200

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximally tolerated dose (MTD) of AVID200

    Cohorts of 3 patients with a maximum evaluable sample size of 12 patients and a target toxicity rate of 30% to estimate the MTD. Each cycle is 21 days.

    Measured: After 6 cycles (Each cycle is 21 days)

  2. Number of patients with response eligibility for Phase 1b

    Subjects attaining at least a CI (clinical improvement) by IWG/ELN criteria, or a decrease in bone marrow fibrosis by ≥1 grade with otherwise stable disease, will be allowed to continue AVID200 in the extension phase of the trial.

    Measured: After 6 cycles

Secondary outcomes (4)

  1. IWG/ELN criteria

    response by IWG/ELN criteria at the end of Cycle 6 and Cycle 12. The IWG/ELN criteria: CR (complete remission), PR (partial remission), Clinical improvement, Anemia response, Spleen response, Symptoms response, PD (progressive disease), SD (stable disease), Relapse, Cytogenetic remission, and Molecular remission

    Measured: After 6 cycles and after 12 cycles (Each cycle is 21 days)

  2. Bone marrow fibrosis grade

    bone marrow fibrosis grade at the end of Cycle 6 and 12. Bone marrow fibrosis (MF) is graded as MF-0 to MF-3, with higher number indicating more disease.

    Measured: up to 37 days after 13 cycles (Each cycle is 21 days)

  3. Myelofibrosis Symptom Assessment Form (MFSAF)

    MF-SAFv4.0,each of the items are scored 0 to 10, with total summation from 0 to 100, with higher score indicating more symptoms.

    Measured: up to 37 days after 13 cycles (Each cycle is 21 days)

  4. EORTC QLQ-C30

    EORTC QLQ-C30, 28 item scored from 1 (not at all) to 4 (very much), and 2 items scored 1 (very poor) to 7 (excellent). Total score from 28 - 126, with higher score indicating poorer health

    Measured: up to 37 days after 13 cycles (Each cycle is 21 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Mar 2019
  2. Study start15 Feb 2019
  3. Primary completion16 May 2022
  4. Study completion16 May 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03895112
Sponsor's protocol ID
GCO 07-0548-01401
Other IDs
P01CA108671, MPN-RC 118
Status last verified
Feb 2023
First submitted
22 Mar 2019
Last updated
10 Feb 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Varricchio L, Mosoyan G, Elghaity-Beckley S, Mia MB, Handa S, Salib C, Mascarenhas J, Hoffman R. Thrombocytopenia in myelofibrosis is characterized by inflammatory megakaryocytes with reduced G6B expression. Blood. 2025 Sep 25;146(13):1612-1624. doi: 10.1182/blood.2024027363.

    PubMed 40643151

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AVID200 in people with Primary Myelofibrosis and Post-essential Thrombocythemia Myelofibrosis, run by John Mascarenhas at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximally tolerated dose (MTD) of AVID200 (time frame: After 6 cycles (Each cycle is 21 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03895112, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in