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A Phase I/II Study of OPN-305 in Second-line Lower Risk Myelodysplastic Syndrome

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. Read our disclaimer for details. Identifier: NCT02363491
Recruitment Status : Completed
First Posted : February 16, 2015
Last Update Posted : January 28, 2019
M.D. Anderson Cancer Center
Montefiore Medical Center
H. Lee Moffitt Cancer Center and Research Institute
New York Presbyterian Hospital
Information provided by (Responsible Party):
Opsona Therapeutics Ltd.

Brief Summary:
The dose-confirming part of this study, comprising at least 10 patients is designed as a single center, prospective, single arm, open label in patients who have failed or are unresponsive to Azacitidine (AZA) or Decitabine (they may also have additionally failed an Erythropoiesis Stimulating Agent (ESA) followed by a dose expansion part with at least 44 patients; the objective of the whole study being to assess the safety, efficacy, pharmacokinetics and pharmacodynamics of intravenously infused multiple doses of OPN-305 in low and intermediate-1 risk myelodysplastic syndrome (second and third line Lower risk MDS).

Condition or disease Intervention/treatment Phase
Myelodysplastic Syndrome Drug: OPN-305 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 96 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Prospective, Open Label Phase I/II Study to Assess the Safety and Efficacy of Cycles of Intravenously Infused Doses of OPN-305 in Second-line or Third-line Lower (Low and Intermediate-1) Risk Myelodysplastic Syndrome (MDS)
Study Start Date : January 2015
Actual Primary Completion Date : December 2018
Actual Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: OPN-305
Drug: OPN-305
For the dose confirming part of the study, patients will receive a starting dose of 5 mg/kg OPN-305.

Primary Outcome Measures :
  1. Establishment of the dose and dose frequency based on dose-limiting toxicity and bone marrow receptor occupancy of OPN-305 in low and intermediate -1 (Lower) risk MDS [ Time Frame: 8 weeks ]
  2. Tolerability of OPN-305 as monotherapy based on adverse events [ Time Frame: 16 weeks/32 weeks (if there is no AZA add-back) ]
  3. Tolerability of OPN-305 as monotherapy and in combination with AZA based on adverse events [ Time Frame: 32 weeks ]

Secondary Outcome Measures :
  1. Hematological response based on International Working Group (IWG) 2000/2006 [ Time Frame: week 36 ]
  2. Cytokine levels in serum (TNFα, IL-1β, IL-6, IL-10, IL-12, IL-18, IL-23 and IFN-γ) [ Time Frame: day 1 and week 4 ]
  3. Immunogenicity of OPN-305 (Measurement of anti drug antibodies and neutralizing antibodies) [ Time Frame: day 1, weeks 4, 8, 16, 24 and 32 ]
  4. Incidence of infections [ Time Frame: 36 weeks ]
  5. Pharmacokinetic profile of OPN-305 (maximum concentration (Cmax)) [ Time Frame: day 1, weeks 4, 8, 12, 16, 20, 24, 28, 32 ]
  6. Pharmacokinetic profile of OPN-305 (time at which Cmax is attained (tmax)) [ Time Frame: day 1, weeks 4, 8, 12, 16, 20, 24, 28, 32 ]
  7. OPN-305 receptor occupancy in peripheral monocytes, bone marrow cells and stroma [ Time Frame: screening (bone marrow only), day 1 (blood only), wks 4 (blood only), 8, 12 (blood only), 16, 20 (blood only), 24 (blood only), 28 (blood only), 32 and 36 (blood only) ]
  8. Correlation of clinical response with cytogenical observations [ Time Frame: wk 36 ]
  9. Quality of life MD Anderson Symptom Inventory (MDASI) - Acute Myeloid Leukemia (AML)/Myelodysplastic syndrome (MDS) questionnaire [ Time Frame: wk 36 ]

    MDASI is MD Anderson symptom inventory. It has two scales

    1. Severity of symptoms scale 0-10 with 0 being not present and 10 being as bad as you can imagine
    2. How symptoms interfere with life scale 0-10 with 0 did not interfere and 10 interfere completely

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Written informed consent
  • Age ≥ 18 years
  • Diagnosis of MDS (de novo or secondary) by bone marrow aspirate based on the World Health Organization (WHO) classification - Low and Intermediate-1 risk categories MDS using the IPSS (International Prognostic Scoring System)
  • AZA/decitabine (this applies to standard of care and investigational drugs) failure (Dose confirming and Dose expansion parts):
  • defined as discontinuation due to any of the following:

    • Lack of response after at least 4 cycles
    • Loss of response (patient must have received therapy for at least 4 cycles)
    • Progressive disease
    • Adverse events

Note: Patients are eligible if additionally they have failed an ESA

  • HMA Naïve group:

    • Never received a hypomethylating agent for MDS
    • Failed or ceased to respond to ESA(s)
    • ESA ineligible; defined as endogenous serum erythropoietin level > 200 U/L for subjects not previously treated with ESAs
  • Red blood cell transfusion dependent defined as ≥ 2 Red blood cells (RBC) units required in the 8 weeks prior to starting in the study. In addition, there should be no 8 consecutive weeks without red blood cell transfusions in the 16 weeks prior to enrolment.
  • Life expectancy ≥ 3 months
  • Eastern Cooperative Oncology Group (ECOG) performance status Grade 0-2
  • Serum bilirubin levels ≤2 x upper limits of normal (ULN)
  • Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels ≤2.5 x ULN
  • Del 5q patients who have failed or are not eligible for Revlimid
  • Creatinine clearance >30 ml/min calculated by the Cockcroft-Gault formula
  • Willingness to comply with the protocol procedures for the duration of the study, including scheduled follow-up visits and examinations
  • Negative urine β-human chorionic gonadotropin (β-HCG) pregnancy test for fertile women at screening and confirmed by serum pregnancy test in the 48 hours prior to OPN-305 administration
  • If sexually active female, patient must be/have one of the following:
  • Post-menopausal defined as the absence of menses for at least one year (serum Follicle-stimulating hormone (FSH) ≥20IU/L can also be measured according to local practice),OR
  • Surgically sterile defined as a bilateral tubal ligation at least 6 months prior to administration of study drug, bilateral oophorectomy, or complete hysterectomy, OR
  • Using an effective means of contraception that is planned to continue for the duration of treatment and for a further 3 months.
  • If sexually active male, patient must: Agree to use an effective means of contraception (per site-specific guidelines) that is planned to continue until 6 months after the last dose of OPN-305.Agree not to donate sperm until 6 months after the last dose of OPN-305

Exclusion Criteria:

  • Diagnosis of MDS by bone marrow aspirate of Intermediate-2 and High risk category MDS based on the World Health Organization (WHO) classification using the IPSS (International Prognostic Scoring System)
  • Patients with 5q deletion (del) MDS eligible for Revlimid (lenalidomide)
  • Hypomethylating agent (HMA) Naïve group:

    • Have received a hypomethylating agent for MDS
    • Have not failed or ceased to respond to an ESA
    • Are not ESA ineligible as defined in inclusion criteria
  • Prior history of acute leukemia or AML
  • Unable/unwilling to undergo bone marrow sampling
  • Prior history of bone marrow transplantation
  • Prior malignancy (other than non-invasive malignancy including in situ cervical cancer, Bowen's disease, basal cell cancer of the skin and non-invasive or excised skin squamous cell carcinoma) unless treated with curative intent and without evidence of disease for 3 years before randomization
  • Active viral or bacterial infections: this includes any infections that are being actively treated even if the signs and symptoms appear to have resolved. Courses of antibiotics or anti-viral treatment should be completed before the patients is enrolled
  • Unstable angina, congestive heart failure [NYHA (New York Heart Association) >class II], uncontrolled hypertension [diastolic > 100 mmHg], uncontrolled cardiac arrhythmia, or recent (within 1 year) myocardial infarction, uncontrolled diabetes mellitus
  • Clinical Evidence of Central Nervous System (CNS) disease
  • Less than 4 weeks since any therapy for MDS
  • Prior history of anaphylaxis to similar products
  • History or presence of a medical condition or disease or substance abuse that in the investigator's assessment would place the patient at an unacceptable risk for study participation
  • Lactating or pregnant woman

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 identifier (NCT number): NCT02363491

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United States, Florida
Research Site
Tampa, Florida, United States, 33613
United States, New York
Research Site
Bronx, New York, United States, 10467
Research Site
New York, New York, United States, 10021
United States, Texas
Research Site
Houston, Texas, United States, 77030
Sponsors and Collaborators
Opsona Therapeutics Ltd.
M.D. Anderson Cancer Center
Montefiore Medical Center
H. Lee Moffitt Cancer Center and Research Institute
New York Presbyterian Hospital
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Principal Investigator: Guillermo Garcia Manero, MD M.D. Anderson Cancer Center

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Responsible Party: Opsona Therapeutics Ltd. Identifier: NCT02363491     History of Changes
Other Study ID Numbers: OPN-305-106
First Posted: February 16, 2015    Key Record Dates
Last Update Posted: January 28, 2019
Last Verified: January 2019
Additional relevant MeSH terms:
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Myelodysplastic Syndromes
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions