Polycythemia Vera, Post-Polycythemic Myelofibrosis PhasePhase 1NCT02871323
Durvalumab in Treating Patients With Primary, Post-Polycythemia Vera, or Post-Essential Thrombocythemia Myelofibrosis
A Phase 1 study testing Durvalumab and Laboratory Biomarker Analysis in people with Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase and Primary Myelofibrosis, run by Northwestern University at 1 site in United States.
Trial summary
The main purpose of this investigational research study is to determine how safe and tolerable the study drug, MEDI4736 (Durvalumab), is in patients with myelofibrosis (MF). The study drug belongs to a group of drugs called immune checkpoint inhibitors, which have shown promise in other forms of cancer, such as… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase, Primary Myelofibrosis
- What is being tested?
- Durvalumab and Laboratory Biomarker Analysis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2016to Nov 2016
- 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
- Patients must have a histologically confirmed diagnosis of primary myelofibrosis (PMF), post-polycythemia vera (post-PV) myelofibrosis (MF), or post-essential thrombocythemia (post-ET) MF using World Health Organization Criteria
- Patients must have disease that requires therapy, including intermediate-1, intermediate-2, or high-risk disease according to the International Prognostic Scoring System (IPSS) or Dynamic-IPSS
- Patients must be resistant to, intolerant of, or ineligible for Janus kinase (JAK)2 inhibitor therapy, or have refused such therapy
- Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
- Patients must have adequate organ and bone marrow function within 14 days prior to registration, as defined below:
- Absolute neutrophil count >= 1.0 x 10^9/L
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- Platelets >= 75 x 10^9/L
- Total bilirubin =< institutional upper limit of normal (ULN) (or =< 3 X ULN if Gilbert's syndrome present or if bilirubin increase related to MF)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase[SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SPGT]) =< 2.5 X institutional ULN
- Creatinine clearance >= 50 mL/min/1.73 m^2 (calculated by estimated glomerular filtration rate [eGFR] from EPIC)
- Female subjects who are pregnant or breast-feeding are not eligible; should a female patient become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; likewise, should a female partner of a male patient become pregnant or suspect she is pregnant while participating in the study, he should inform his treating physician and the female partner should call her physician immediately
- Female of child bearing potential (FOCBP) must have a negative pregnancy test (serum or urine) within 7 days prior to registration on study; NOTE: A FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
- Has not undergone a hysterectomy or bilateral oophorectomy
- Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months)
- Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study
Who cannot join
- Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis, Crohn's disease], diverticulitis with the exception of a prior episode that has resolved or diverticulosis, celiac disease, irritable bowel disease, or other serious gastrointestinal chronic conditions associated with diarrhea; systemic lupus erythematosus; Wegener's syndrome [granulomatosis with polyangiitis]; myasthenia gravis; Graves' disease; rheumatoid arthritis; hypophysitis, uveitis; etc.) within the past 3 years prior to the start of treatment
- The following are exceptions to this criterion: subjects with vitiligo or alopecia; subjects with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement; or subjects with psoriasis not requiring systemic treatment
- Known human immunodeficiency virus (HIV), hepatitis C virus (HCV) or evidence of active hepatitis B virus (HBV)
- Current or prior use of immunosuppressive medication within 14 days prior to first dose of durvalumab; the following are exceptions to this criterion: intranasal, inhaled, topical or local steroid injections (eg. intra-articular injection); steroids as premedication for hypersensitivity reactions; systemic corticosteroid at physiologic doses not to exceed 10 mg/day of prednisone or equivalent; (NOTE: If systemic corticosteroids are part of the treatment regimen for the indication under study, the systemic corticosteroid is permitted)
- Female subjects who are pregnant, breast-feeding or female patients of reproductive potential who are not employing an effective method of birth control from starting dose of durvalumab (cycle 1 day 1), including dosing interruptions through 90 days after receipt of the last dose of durvalumab are not eligible; female subjects should agree to refrain from egg cell donation while taking durvalumab and for at least 90 days after the last dose of durvalumab
- Male subjects who are not employing an effective method of birth control from starting dose of durvalumab (cycle 1 day 1), including dosing interruptions through 90 days after receipt of the last dose of durvalumab are not eligible; male subjects should agree to refrain from sperm donation while taking durvalumab and for at least 90 days after the last dose of durvalumab; should a female partner of a male patient become pregnant or suspect she is pregnant while participating in the study, he should inform his treating physician and the female partner should call her physician immediately
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- History of hypersensitivity to durvalumab or any excipient
- Receipt of live attenuated vaccination within 30 days prior the first dose of durvalumab
- Patients may not be receiving any other investigational agents within 2 weeks prior to registration
- Patients who have had prior exposure to checkpoint blockade therapy, such as anti-PD-1/PD-L1, anti-cytotoxic T-lymphocyte associated protein 4 (CTLA4), anti-CD137, and anti-OX40 antibody therapy, are not eligible
- Patients who have an inter-current illness including, but not limited to any of the following, are not eligible:
- Severe hypertension that is not controlled on medication (>= 140/90 mmHg for 3 consecutive readings)
- Ongoing or active infection requiring systemic treatment
- Congestive heart failure with New York Heart Association (NYHA) classification of 3
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness/social situations that would limit compliance with study requirements
- Patients with another malignancy, unless they have been disease free for 3 years prior to registration (with the exception of squamous cell carcinoma or basal cell carcinoma of the skin or cervical intraepithelial neoplasia)
- Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints
- Unwilling or unable to comply with the protocol
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1, Single Arm, Single Center Pilot Study of Medi4736, an Anti-Pdl1 Therapy, for Patients With Myelofibrosis
The main purpose of this investigational research study is to determine how safe and tolerable the study drug, MEDI4736 (Durvalumab), is in patients with myelofibrosis (MF). The study drug belongs to a group of drugs called immune checkpoint inhibitors, which have shown promise in other forms of cancer, such as melanoma and lung cancer. One of the effects that this drug has is to activate the patient's own natural immune system. The purpose of this study is to examine the safety and tolerability of the study drug, to study how effective it is at treating patients with myelofibrosis, and to explore how certain markers in the patient's blood and/or bone marrow may be affected by the study drug.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the safety profile of anti-programmed cell death 1 ligand 1 (PDL1) therapy in patients with myelofibrosis.
SECONDARY OBJECTIVES:
- Changes in MF symptom burden. II. Changes in spleen size. III. Blood and/or bone marrow samples.
TERTIARY OBJECTIVES:
- To determine the rate of lymphocyte subset response to anti-PDL1 therapy, as measured by the percent increase in cluster of differentiation (CD)4+CD25+PD-L1+ T-lymphocytes and CD4+CD62L+CD127+ T lymphocytes in post-treatment peripheral blood samples.
II. To characterize changes in the cytokine profile in response to anti-PDL1 therapy.
III. To measure soluble PDL1 by enzyme-linked immunosorbent assay (ELISA) in post-treatment blood and/or bone marrow samples and programmed cell death-1 (PD1)/PDL1 by immunohistochemistry on bone marrow samples and correlate with treatment response.
OUTLINE:
Patients receive durvalumab intravenously (IV) over approximately 1 hour on day 1. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients with stable disease (SD), no new inter-current illness, and no unacceptable toxicity, may continue treatment beyond 3 courses.
Patients will be followed every 3 months for up to two years starting from Day 1.
- Being tested
- Durvalumab, Laboratory Biomarker Analysis
- Keywords
- Myelofibrosis Transformation in Essential Thrombocythemia
- Medical subject headings
- Polycythemia Vera, Primary Myelofibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DurvalumabBiological
Also called Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736
Given IV
Laboratory Biomarker AnalysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (durvalumab) | Experimental | Patients receive durvalumab IV over approximately 1 hour on day 1. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients with SD, no new inter-current illness, and no unacceptable toxicity, may continue treatment beyond 3 courses. Receives: Biological: Durvalumab; Other: Laboratory Biomarker Analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Adverse Events
To determine the safety profile of anti-PDL1 therapy in patients with myelofibrosis, adverse events will be assessed by number, frequency, and severity according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
Measured: Up to 2 years
Secondary outcomes (4)
Changes in MF symptom burden
Changes in MF symptom burden will be assessed using the validated Patient Reported Outcome tool called the Myeloproliferative Neoplasm (MPN)-Symptom Assessment Form (SAF).
Measured: Baseline up to 2 years
Changes in spleen size
Change in spleen size will be assessed by physical examination (palpation) OR ultrasound as part of standard of care.
Measured: Baseline up to 2 years
Response to anti-PDL1 treatment in blood
Response to anti-PDL1 treatment will be defined in accordance with the revised/modified International Working Group (IWG) Response Criteria and will be assessed by blood samples.
Measured: Up to 2 years
Response to anti-PDL1 treatment in bone marrow
Response to anti-PDL1 treatment will be defined in accordance with the revised/modified International Working Group (IWG) Response Criteria and will be assessed by bone marrow samples.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2016 (estimated)
- Study startNov 2016
- Primary completionNov 2016 (estimated)
Why it stopped: PI decided to withdraw the study after it opened for enrollment but before any patients were enrolled
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Polycythemia Vera, Post-Polycythemic Myelofibrosis PhaseStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Collaborators
- Celgene, The Leukemia and Lymphoma Society, National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Brady Stein, MD, MHS, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02871323
- Sponsor's protocol ID
- NU 16H05
- Other IDs
- STU00202833, NU 16H05, P30CA060553, NCI-2016-01024
- Status last verified
- Aug 2019
- First submitted
- 9 Aug 2016
- Last updated
- 20 Aug 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Single Arm, Single Center Pilot Study of Medi4736, an Anti-Pdl1 Therapy, for Patients With Myelofibrosis
- ClinicalTrials.gov ID
- NCT02871323
- Acronym / sponsor ID
- NU 16H05
- Keywords
- Myelofibrosis Transformation in Essential Thrombocythemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: PI decided to withdraw the study after it opened for enrollment but before any patients were enrolled
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Collaborators
- Celgene, The Leukemia and Lymphoma Society, National Cancer Institute (NCI)
- Study start
- Nov 2016
- Primary completion
- Nov 2016 (estimated)
- First posted
- 18 Aug 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main purpose of this investigational research study is to determine how safe and tolerable the study drug, MEDI4736 (Durvalumab), is in patients with myelofibrosis (MF). The study drug belongs to a group of drugs called immune checkpoint inhibitors, which have shown promise in other forms of cancer, such as melanoma and lung cancer. One of the effects that this drug has is to activate the patient's own natural immune system. The purpose of this study is to examine the safety and tolerability of the study drug, to study how effective it is at treating patients with myelofibrosis, and to explore how certain markers in the patient's blood and/or bone marrow may be affected by the study drug.
Detailed description
PRIMARY OBJECTIVES:
- To determine the safety profile of anti-programmed cell death 1 ligand 1 (PDL1) therapy in patients with myelofibrosis.
SECONDARY OBJECTIVES:
- Changes in MF symptom burden. II. Changes in spleen size. III. Blood and/or bone marrow samples.
TERTIARY OBJECTIVES:
- To determine the rate of lymphocyte subset response to anti-PDL1 therapy, as measured by the percent increase in cluster of differentiation (CD)4+CD25+PD-L1+ T-lymphocytes and CD4+CD62L+CD127+ T lymphocytes in post-treatment peripheral blood samples.
II. To characterize changes in the cytokine profile in response to anti-PDL1 therapy.
III. To measure soluble PDL1 by enzyme-linked immunosorbent assay (ELISA) in post-treatment blood and/or bone marrow samples and programmed cell death-1 (PD1)/PDL1 by immunohistochemistry on bone marrow samples and correlate with treatment response.
OUTLINE:
Patients receive durvalumab intravenously (IV) over approximately 1 hour on day 1. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients with stable disease (SD), no new inter-current illness, and no unacceptable toxicity, may continue treatment beyond 3 courses.
Patients will be followed every 3 months for up to two years starting from Day 1.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (durvalumab) | Experimental | Biological: Durvalumab, Other: Laboratory Biomarker AnalysisPatients receive durvalumab IV over approximately 1 hour on day 1. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients with SD, no new inter-current illness, and no unacceptable toxicity, may continue treatment beyond 3 courses. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Patients must have a histologically confirmed diagnosis of primary myelofibrosis (PMF), post-polycythemia vera (post-PV) myelofibrosis (MF), or post-essential thrombocythemia (post-ET) MF using World Health Organization Criteria
- Patients must have disease that requires therapy, including intermediate-1, intermediate-2, or high-risk disease according to the International Prognostic Scoring System (IPSS) or Dynamic-IPSS
- Patients must be resistant to, intolerant of, or ineligible for Janus kinase (JAK)2 inhibitor therapy, or have refused such therapy
- Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
- Patients must have adequate organ and bone marrow function within 14 days prior to registration, as defined below:
Key exclusion criteria (20 listed)
- Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis, Crohn's disease], diverticulitis with the exception of a prior episode that has resolved or diverticulosis, celiac disease, irritable bowel disease, or other serious gastrointestinal chronic conditions associated with diarrhea; systemic lupus erythematosus; Wegener's syndrome [granulomatosis with polyangiitis]; myasthenia gravis; Graves' disease; rheumatoid arthritis; hypophysitis, uveitis; etc.) within the past 3 years prior to the start of treatment
- Known human immunodeficiency virus (HIV), hepatitis C virus (HCV) or evidence of active hepatitis B virus (HBV)
- Current or prior use of immunosuppressive medication within 14 days prior to first dose of durvalumab; the following are exceptions to this criterion: intranasal, inhaled, topical or local steroid injections (eg. intra-articular injection); steroids as premedication for hypersensitivity reactions; systemic corticosteroid at physiologic doses not to exceed 10 mg/day of prednisone or equivalent; (NOTE: If systemic corticosteroids are part of the treatment regimen for the indication under study, the systemic corticosteroid is permitted)
- Female subjects who are pregnant, breast-feeding or female patients of reproductive potential who are not employing an effective method of birth control from starting dose of durvalumab (cycle 1 day 1), including dosing interruptions through 90 days after receipt of the last dose of durvalumab are not eligible; female subjects should agree to refrain from egg cell donation while taking durvalumab and for at least 90 days after the last dose of durvalumab
- Male subjects who are not employing an effective method of birth control from starting dose of durvalumab (cycle 1 day 1), including dosing interruptions through 90 days after receipt of the last dose of durvalumab are not eligible; male subjects should agree to refrain from sperm donation while taking durvalumab and for at least 90 days after the last dose of durvalumab; should a female partner of a male patient become pregnant or suspect she is pregnant while participating in the study, he should inform his treating physician and the female partner should call her physician immediately
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DurvalumabAlso: Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736Given IV | Biological | Treatment (durvalumab) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (durvalumab) |
Primary outcome
Incidence of Adverse Events
Time frame: Up to 2 years
To determine the safety profile of anti-PDL1 therapy in patients with myelofibrosis, adverse events will be assessed by number, frequency, and severity according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
4 secondary outcomes
Changes in MF symptom burden
Time frame: Baseline up to 2 years
Changes in spleen size
Time frame: Baseline up to 2 years
Response to anti-PDL1 treatment in blood
Time frame: Up to 2 years
Response to anti-PDL1 treatment in bone marrow
Time frame: Up to 2 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brady Stein, MD, MHS principal investigator
Northwestern University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Durvalumab and Laboratory Biomarker Analysis in people with Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase and Primary Myelofibrosis, run by Northwestern University 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 15 inclusion and 20 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: withdrawn, as of the sponsor's last update on 20 Aug 2019. 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 was withdrawn before enrolling participants, so there are no results.
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?
Incidence of Adverse Events (time frame: Up to 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Aug 2019.