Polycythemia VeraPhase 2NCT03287245
A Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Idasanutlin Monotherapy in Participants With Hydroxyurea-Resistant/Intolerant Polycythemia Vera
A Phase 2 study testing Idasanutlin in people with Polycythemia Vera, run by Hoffmann-La Roche at 11 sites in 4 countries.
Trial summary
This is an open-label, single-arm study of idasanutlin monotherapy in participants with hydroxyurea (HU)-resistant/intolerant Polycythemia vera (PV). The study will include two phases: initial phase and expansion phase. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Polycythemia Vera
- What is being tested?
- Idasanutlin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 11 sitesin 4 countries
- Study dates
- 21 Feb 2018to 3 Mar 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Documentation that the participant has met the revised 2016 World Health Organization (WHO) criteria for the diagnosis of polycythemia vera (PV)
- Hematocrit at screening and at initiation of idasanutlin greater than (>)40%
- Phlebotomy-dependent participants with splenomegaly by magnetic resonance imaging (MRI) or computerized tomography (CT) imaging (greater than or equal to [≥]450 cubic centimeters [cm^3]) or without splenomegaly (less than [<]450 cm^3 or prior splenectomy)
- Resistance to/intolerance to hydroxyurea according to modified European Leukemia Net (ELN) criteria
- For participants in the ruxolitinib intolerant or resistant group, in addition to previous hydroxyurea intolerance/resistance: Therapy-resistant PV after at least 6 months of treatment with ruxolitinib, as defined in the protocol; Ruxolitinib intolerance, as defined in the protocol; and Documentation of adverse events likely caused by ruxolitinib (assessment of attending physician) and that are of a severity that preclude further treatment with ruxolitinib (as per judgment of the attending physician and the patient)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
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- Participants must be willing to submit the blood sampling and bone marrow sampling for the pharmacokinetic (PK) and pharmacodynamic analyses and exploratory biomarkers
- Adequate hepatic and renal function
- Ability and willingness to comply with the study protocol procedures, including clinical outcome assessment measures
- For women of childbearing potential: agreement to use contraceptive methods that result in a failure rate of less than (<)1% per year during the treatment period and for at least 6 weeks after the last dose of idasanutlin
- For men: Agreement to use contraceptive measures, and agreement to refrain from donating sperm during the treatment period and for at least 90 days after the last dose of idasanutlin
Who cannot join
- Meets the criteria for post-PV myelofibrosis as defined by the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT)
- Blast phase disease (>20% blasts in the marrow or peripheral blood)
- Clinically-significant thrombosis within 3 months of screening
- Participants who must receive CYP2C8 inhibitors, substrates and inducers, strong CYP3A4 inducers, or OATP1B1/3 substrates while on study. These must be discontinued 7 days (inhibitors and substrates) or 14 days (inducers) prior to start of study medication
- Previously treated with murine double minute 2 (MDM2) antagonist therapies or receiving interferon-alpha, anagrelide, or ruxolitinib within 28 days or 5 half-lives (whichever is shorter), or hydroxyurea within 1 day, or receiving any other cytoreductive or investigational agents within 28 days or 5 half-lives (whichever is shorter) of initial dose. Aspirin is permitted per treatment guidelines for PV unless medically contraindicated
- Patients with evidence of electrolyte imbalance such as hypokalemia, hyperkalemia, hypocalcemia, hypercalcemia, hypomagnesemia, and hypermagnesemia of Grade >1 intensity, as per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0, prior to dosing on Cycle 1 Day 1. Treatment for correction of electrolyte imbalances is permitted to meet eligibility
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- Neutrophil count <1.5 × 10^9/Liter (L) prior to dosing on Cycle 1 Day 1
- Platelet count less than or equal to (≤)150 × 10^9/L prior to dosing on Cycle 1 Day 1
- Women who are pregnant or breastfeeding
- Ongoing serious non-healing wound, ulcer, or bone fracture
- History of major organ transplant
- Uncontrolled intercurrent illness including, but not limited to hepatitis, concurrent malignancy that could affect compliance with the protocol or interpretation of results, hepatitis A, B, and C, human immunodeficiency virus (HIV)-positive, ongoing or active infection, clinically significant cardiac disease (New York Heart Association Class III or IV), symptomatic congestive heart failure, unstable angina pectoris, ventricular arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Concurrent malignancy exceptions include: Curatively treated carcinoma in situ of the cervix, good-prognosis ductal carcinoma in situ of the breast, basal- or squamous-cell skin cancer, Stage I melanoma, or low-grade, early-stage localized prostate cancer. Any previously treated early-stage non-hematological malignancy that has been in remission for at least 2 years is also permitted.
- Patients with active gastrointestinal conditions (Crohn's disease, ulcerative colitis, diverticulosis associated colitis, and Behçet's disease)
- Clinically significant toxicity (other than alopecia) from prior therapy that has not resolved to Grade ≤1 (according to the NCI CTCAE, v4.0) prior to Cycle 1 Day 1
- Cardiovascular disease, such as: uncontrolled arterial hypertension; symptomatic congestive heart failure or ejection fraction below 55% at screening, or left ventricular hypertrophy; any significant structural abnormality of the heart at screening echocardiogram; unstable angina pectoris; presence or history of any type of supraventricular and ventricular arrhythmias, including lone atrial fibrillation or flutter
Trial locations and contacts
11 sites in 4 countries.
11 sites in 4 countries
United States5 sites
Cleveland Clinic Cancer Center
Independence, Ohio, 44131
University of Kansas Cancer Center; Westwood Cancer Center/BMT Output Clinic
Kansas City, Kansas, 66205
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
Mayo Clinic - Arizona
Phoenix, Arizona, 85054
University of Texas Health Sciences Center in San Antonio
San Antonio, Texas, 78229
Italy3 sites
ASST PAPA GIOVANNI XXIII; Ematologia
Bergamo, Lombardy, 24127
Az. Ospedaliero-Universitaria Careggi; CRIMM
Florence, Tuscany, 50134
Ospedale Di Circolo E Fondazione Macchi; Ematologia
Varese, Lombardy, 21100
Australia2 sites
Royal Adelaide Hospital; Haematology Clinical Trials
Adelaide, South Australia, 5000
Peter MacCallum Cancer Centre; Department of Haematology
Melbourne, Victoria, 3002
About this study
Official title: A Phase II, Single-Arm, Open-Label Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Idasanutlin Monotherapy in Patients With Hydroxyurea-Resistant/Intolerant Polycythemia Vera
This is an open-label, single-arm study of idasanutlin monotherapy in participants with hydroxyurea (HU)-resistant/intolerant Polycythemia vera (PV). The study will include two phases: initial phase and expansion phase. The initial phase will assess the safety and efficacy of idasanutlin monotherapy in ruxolitinib naïve and ruxolitinib-resistant or intolerant patients, respectively. If the initial phase shows promising results for ruxolitinib-resistant or intolerant patients, an expansion phase will be opened to further characterize the efficacy of idasanutlin.
- Conditions
- Polycythemia Vera
- Being tested
- Idasanutlin
- Keywords
- polycythemia vera, PV, P vera, myeloproliferative diseases, hematologic diseases, myeloproliferative neoplasm, MPN
- Medical subject headings
- Polycythemia Vera, Hematologic Diseases, Myeloproliferative Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IdasanutlinDrug
Also called RO5503781, RG7388
All participants will receive 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Intra-participant dose-escalation to 200 mg daily for 5 days may be permitted after Cycle 3 for those who demonstrate no hematocrit (Hct) control and/or for those with inadequately controlled leukocytosis and/or thrombocytosis in which the investigator judges that better control is important.
| Study group | Role | What they receive |
|---|---|---|
| Idasanutlin | Experimental | Two cohorts of ruxolitinib-naïve and ruxolitinib-resitant or intolerant participants will be enrolled to receive idasanutlin once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Receives: Drug: Idasanutlin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Ruxolitinib-Naïve Participants With Splenomegaly at Baseline Who Achieved Composite Response at Week 32
Composite response is defined as hematocrit (Hct) control without phlebotomy and ≥35% decrease in spleen size by imaging at Week 32. Hct control is defined as protocol-specified ineligibility for phlebotomy between Weeks 8 to 32 and ≤1 instance of phlebotomy eligibility between first dose and Week 8. Eligibility for phlebotomy is defined as a Hct of ≥45% that was ≥3% higher than baseline level or a Hct of >48%. One Cycle is 28 Days.
Measured: Week 32
Percentage of Ruxolitinib-Naïve Participants Without Splenomegaly at Baseline Who Achieved Hematocrit (Hct) Control Without Phlebotomy at Week 32
Hct control is defined as protocol-specified ineligibility for phlebotomy between Weeks 8 to 32 and ≤1 instance of phlebotomy eligibility between first dose and Week 8. Eligibility for phlebotomy is defined as a Hct level ≥45% that was ≥3% higher than baseline level or a Hct level of >48%.
Measured: Week 32
Percentage of All Ruxolitinib-Naïve Participants (Irrespective of Spleen Size) Who Achieved Hct Control Without Phlebotomy at Week 32
Hct control is defined as protocol-specified ineligibility for phlebotomy between Weeks 8 to 32 and ≤1 instance of phlebotomy eligibility between first dose and Week 8. Eligibility for phlebotomy is defined as a Hct level ≥45% that was ≥3% higher than baseline level or a Hct level of >48%.
Measured: Week 32
Percentage of All Ruxolitinib-Resistant or Intolerant Participants Who Achieved Hct Control Without Phlebotomy at Week 32
Hct control is defined as protocol-specified ineligibility for phlebotomy between Weeks 8 to 32 and ≤1 instance of phlebotomy eligibility between first dose and Week 8. Eligibility for phlebotomy is defined as a Hct level ≥45% that was ≥3% higher than baseline level or a Hct level of >48%.
Measured: From Baseline to Week 32 (Cycle 8 Day 28)
Secondary outcomes (36)
Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants Who Achieved Complete Hematologic Response at Week 32
Complete hematologic response requires all of the following: Hct control without phlebotomy; White blood cell (WBC) count ≤10 × 10^9/Liter (L) at Week 32; and Platelet count ≤400 × 10^9/L at Week 32. Hct control is defined as protocol-specified ineligibility for phlebotomy between Weeks 8 to 32 and ≤1 instance of phlebotomy eligibility between first dose and Week 8. Eligibility for phlebotomy is defined as a Hct level ≥45% that was ≥3% higher than baseline level or a Hct level of >48%.
Measured: Week 32 (Cycle 8 Day 28)
Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants Who Achieved Complete Hematologic Remission at Cycle 11 Day 28
Complete hematologic remission requires all of the following: Hct control without phlebotomy between Weeks 32 and Cycle 11 Day 28; WBC count ≤10 × 10^9/L at Cycle 11 Day 28; and Platelet count ≤400 × 10^9/L at Week 32. Hct control is defined as protocol-specified ineligibility for phlebotomy. Eligibility for phlebotomy is defined as a Hct level ≥45% that was ≥3% higher than baseline level or a Hct level of >48%.
Measured: Cycle 11 Day 28
Duration of Complete Hematologic Remission, With a Durable Responder Defined as a Participant in Remission at Week 32 and Cycle 11 Day 28
Complete hematologic remission requires all of the following: Hct control without phlebotomy between Week 32 (Cycle 8 Day 28) and Cycle 11 Day 28; WBC count ≤10 × 10^9/L at Cycle 11 Day 28; and Platelet count ≤400 × 10^9/L at Week 32. Hct control is defined as protocol-specified ineligibility for phlebotomy. Eligibility for phlebotomy is defined as a Hct level ≥45% that was ≥3% higher than baseline level or a Hct level of >48%
Measured: Week 32 (Cycle 8 Day 28), Cycle 11 Day 28
Percentage of Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly at Baseline by Response Per Modified European Leukemia Net (ELN) Criteria
Complete response (CR) includes all of the following: Hct <45% without phlebotomy; Platelet count ≤400 × 10^9/L; WBC count ≤10 × 10^9/L; Normal spleen size on imaging; and No disease-related symptoms. Partial response (PR): in participants who do not fulfill the criteria for CR: Hct <45% without phlebotomy or response in 3 or more of the other criteria. No response (NR): any response that does not satisfy partial response. Progressive disease (PD): increased bone marrow fibrosis from baseline, and/or transformation to myelofibrosis (MF), myelodysplastic syndrome (MDS) or acute leukemia.
All responders of each category grouped per timepoint include all categories mentioned above. There were no PD responses at any timepoint.
The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the end of study.
Measured: Baseline, Day 28 of Cycles 3, 5, 8, 11, 12, 14, 17, 20 and Final visit (28 days after post-last dose)
Percentage of Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly at Baseline by Response Per Modified ELN Criteria
Complete response (CR) includes all of the following: Hct <45% without phlebotomy; Platelet count ≤400 × 10^9/L; WBC count ≤10 × 10^9/L; Normal spleen size on imaging; and No disease-related symptoms. Partial response (PR): in participants who do not fulfill the criteria for CR: Hct <45% without phlebotomy or response in 3 or more of the other criteria. No response (NR): any response that does not satisfy partial response. Progressive disease (PD): increased bone marrow fibrosis from baseline, and/or transformation to myelofibrosis (MF), myelodysplastic syndrome (MDS) or acute leukemia.
All responders of each category grouped per timepoint include all categories mentioned above. There were no PD responses at any timepoint.
The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the end of study.
Measured: Baseline, Day 28 of Cycles 3, 5, 8, 11, 12, 14, 17, 20 and Final visit (28 days after post-last dose)
Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants (Irrespective of Spleen Size) by Response Per Modified ELN Criteria
Complete response (CR) includes all of the following: Hct <45% without phlebotomy; Platelet count ≤400 × 10^9/L; WBC count ≤10 × 10^9/L; Normal spleen size on imaging; and No disease-related symptoms. Partial response (PR): in participants who do not fulfill the criteria for CR: Hct <45% without phlebotomy or response in 3 or more of the other criteria. No response (NR): any response that does not satisfy partial response. Progressive disease (PD): increased bone marrow fibrosis from baseline, and/or transformation to myelofibrosis (MF), myelodysplastic syndrome (MDS) or acute leukemia.
All responders of each category grouped per timepoint include all categories mentioned above. There were no PD responses at any timepoint.
The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the end of study.
Measured: Baseline, Day 28 of Cycles 3, 5, 8, 11, 12, 14, 17, 20 and Final visit (28 days after post-last dose)
Percentage of Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly at Baseline With Durable Response Lasting at Least 12 Weeks From Week 32
The percentage of participants with a durable response lasting at least 12 weeks from Week 32 are analyzed by the type of response achieved: Hct control, complete hematologic response, ELN 2009 response criteria, and composite response, if applicable.
Reported result data start from Cycle 11 Day 28 which is 12 weeks after Week 32 (Cycle 8 Day 28). There was one timepoint for which the participants qualify. The study was pre-maturely terminated by the sponsor decision, therefore did not reach the end of study.
Measured: From Week 32 (Cycle 8 Day 28) and at least 12 Weeks after until end of study (up to 2 years)
Number of Participants With a Durable Response, in Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly at Baseline With Durable Response Lasting at Least 12 Weeks From Week 32
The number of participants with a durable response lasting at least 12 weeks from Week 32 is analyzed by the type of response achieved: Hct control, complete hematologic response, ELN 2009 response criteria, and composite response, if applicable.
Reported result data start from Cycle 11 Day 28 which is 12 weeks after Week 32 (Cycle 8 Day 28). There was one timepoint for which the participants qualify.
The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the planned end of study.
Measured: From Week 32 (Cycle 8 Day 28) and at least 12 weeks after until end of study (up to 2 years)
Percentage of Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly at Baseline With Durable Response Lasting at Least 12 Weeks From Week 32
The percentage of participants with a durable response lasting at least 12 weeks from Week 32 is analyzed by the type of response achieved: Hct control, complete hematologic response, ELN 2009 response criteria, and composite response, if applicable.
Reported result data start from Cycle 11 Day 28 which is 12 weeks after Week 32 (Cycle 8 Day 28). There was one timepoint for which the participants qualify. The study was pre-maturely terminated by the sponsor decision, therefore did not reach the end of study.
Measured: From Week 32 (Cycle 8 Day 28) and at least 12 Weeks after until end of study (up to 2 years)
Number of Participants With a Durable Response, in Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly at Baseline With Durable Response Lasting at Least 12 Weeks From Week 32
The number of participants with a durable response lasting at least 12 weeks from Week 32 is analyzed by the type of response achieved: Hct control, complete hematologic response, ELN 2009 response criteria, and composite response, if applicable.
Reported result data start from Cycle 11 Day 28 which is 12 weeks after Week 32 (Cycle 8 Day 28). There was one timepoint for which the participants qualify.
The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the planned end of study.
Measured: From Week 32 (Cycle 8 Day 28) and at least 12 weeks after until end of study (up to 2 years)
Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants (Irrespective of Spleen Size) With Durable Response Lasting at Least 12 Weeks From Week 32
The percentage of participants with a durable response lasting at least 12 weeks from Week 32 is analyzed by the type of response achieved: Hct control, complete hematologic response, ELN 2009 response criteria, and composite response, if applicable.
Reported result data start from Cycle 11 Day 28 which is 12 weeks after Week 32 (Cycle 8 Day 28). There was one timepoint for which the participants qualify. The study was pre-maturely terminated by the sponsor decision, therefore did not reach the end of study.
Measured: From Week 32 (Cycle 8 Day 28) and at least 12 Weeks after until end of study (up to 2 years)
Number of Participants With a Duration Response, in All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants (Irrespective of Spleen Size) With Durable Response Lasting at Least 12 Weeks From Week 32
The number of participants with a durable response lasting at least 12 weeks from Week 32 is analyzed by the type of response achieved: Hct control, complete hematologic response, ELN 2009 response criteria, and composite response, if applicable.
Reported result data start from Cycle 11 Day 28 which is 12 weeks after Week 32 (Cycle 8 Day 28). There was one timepoint for which the participants qualify.
The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the planned end of study.
Measured: From Week 32 (Cycle 8 Day 28) and at least 12 weeks after until end of study (up to 2 years)
Total Number of Participants With Adverse Events by Severity, Graded According to NCI CTCAE v4.0
An adverse event is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not considered related to the study drug. The adverse event severity grading scale for the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI CTCAE v4.0) will be used for assessing adverse event severity.
During the final analyses, the focus was on the Adverse Events of severity grades >/=3 as shown below. The extensive listings of all grade AEs are available at request.
The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the planned end of study.
Measured: Baseline to end of study (up to 2 years)
Percentage of Participants With Clinical Laboratory Abnormalities: Hematology Parameters.
Hematology parameter laboratory values falling outside the standard reference range were planned to be recorded as either high or low.
There was no clinical laboratory abnormalities identified. The study was pre-maturely terminated by the sponsor's decision, therefore did not reach the end of study.
Measured: Baseline to end of study (up to 2 years)
Percentage of Participants With Clinical Laboratory Abnormalities: Clinical Chemistry Parameters
Clinical chemistry parameter laboratory values falling outside the standard reference range were to be recorded as either high or low.
There was no clinical chemistry abnormalities identified. The study was pre-maturely terminated by the sponsor's decision, therefore did not reach the end of study.
Measured: Baseline to end of study (up to 2 years)
Percentage of Participants With Clinical Laboratory Abnormalities: Urinalysis Parameters
Urinalysis parameter laboratory values falling outside the standard reference range were planned to be recorded as either high or low.
There was no clinical laboratory (urinalysis) abnormalities identified. The study was pre-maturely terminated by the sponsor's decision, therefore did not reach the end of study.
Measured: Baseline to end of study (up to 2 years)
Change From Baseline in Electrocardiogram Parameters: PQ(PR), QRS, QT, QTcB, QTcF, and RR Durations
Single 12-lead ECGs was obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the planned end of study.
Measured: Baseline, Cycle 1 (Day 1, hours 4 and 6, Day 2 pre-dose and 24 Hour, Day 5 pre-dose, 4 and 6 Hour), Cycle 2 (Day 1 pre-dose only), Cycle 3 (Day 1 pre-dose, 4 and 6 Hour), Cycle 4 (Day 1 pre-dose and 4 Hour)
Change From Baseline in Heart Rate, as Measured by Electrocardiogram
Single 12-lead ECGs was obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the planned end of study.
Measured: Baseline, Cycle 1 (Day 1, hours 4 and 6, Day 2 pre-dose and 24 Hour, Day 5 pre-dose, 4 and 6 Hour), Cycle 2 (Day 1 pre-dose only), Cycle 3 (Day 1 pre-dose, 4 and 6 Hour), Cycle 4 (Day 1 pre-dose and 4 Hour)
Change From Baseline in Oral Temperature
Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The study was pre-maturely terminated by the sponsor's decision, therefore did not reach the end of study.
Measured: Baseline, Cycle 1 (Days 15 and 22), Cycle 2 and 3 (Days 1 and 15), Each Cycle 4-23 (Day 1 only) and Final Visit
Change From Baseline in Pulse Rate
Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the planned end of study.
Measured: Baseline, Cycle 1 (Days 15 and 22), Cycle 2 and 3 (Days 1 and 15), Each Cycle 4-23 (Day 1 only) and Final Visit
Change From Baseline in Respiratory Rate
Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the planned end of study.
Measured: Baseline, Cycle 1 (Days 15 and 22), Cycle 2 and 3 (Days 1 and 15), Each Cycle 4-23 (Day 1 only) and Final Visit
Change From Baseline in Systolic Blood Pressure
Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the planned end of study.
Measured: Baseline, Cycle 1 (Days 15 and 22), Cycle 2 and 3 (Days 1 and 15), Each Cycle 4-23 (Day 1 only) and Final Visit
Change From Baseline in Diastolic Blood Pressure
Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the planned end of study.
Measured: Baseline, Cycle 1 (Days 15 and 22), Cycle 2 and 3 (Days 1 and 15), Each Cycle 4-23 (Day 1 only) and Final Visit
Eastern Cooperative Oncology Group (ECOG) Performance Status Over Time
The ECOG performance status is a scale used to quantify cancer patients' general well-being and activities of daily life. The scale ranges from 0 to 5, with 0 denoting perfect health and 5 indicating death. The 6 categories are 0=Asymptomatic (Fully active, able to carry on all pre-disease activities without restriction), 1=Symptomatic but completely ambulatory, 2=Symptomatic, < 50% in bed during the day (Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours), 3=Symptomatic, > 50% in bed, but not bedbound (Capable of only limited self-care, confined to bed or chair 50% or more of waking hours), 4=Bedbound (Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair), 5=Death.
Only baseline data were collectable. The study was pre-maturely terminated by the sponsor's decision, therefore did not reach the planned end of study.
Measured: Baseline
Percentage of Participants With Concomitant Medications
Participants with Concomitant Medications used from 28 days prior to screening until the final visit or end of study (EOS) were reported.
The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study.
Measured: Overall Study Period
Maximum Serum Concentration Observed (Cmax) of Idasanutlin
Cmax is the maximum observed concentration of drug in blood. The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study.
Measured: Days 1, 2, and 5 of Cycles 1 and 4
Trough Concentration (Ctrough) of Idasanutlin
Ctrough is the measured concentration of a drug at the end of a dosing interval at steady state.
The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study.
Measured: Days 1, 2, and 5 of Cycles 1 and 4
Time of Maximum Concentration Observed (Tmax) of Idasanutlin
Tmax is the time elapsed from the time of drug administration to maximum plasma concentration.
The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study.
Measured: Days 1, 2, and 5 of Cycles 1 and 4
Clearance (CL) of Idasanutlin
CL is a measure of the body's elimination of a drug from plasma over time. The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study.
Measured: Days 1, 2, and 5 of Cycles 1 and 4
Apparent Clearance (CL/F) of Idasanutlin
CL/F is a measure of the body's elimination of a drug from plasma over time, after oral administration.
The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study.
Measured: Days 1, 2, and 5 of Cycles 1 and 4
Volume or Apparent Volume of Distribution (Vdss/F) of Idasanutlin
Vdss/F is the theoretical volume that would be necessary to contain the total amount of an administered drug at the same concentration that it is observed in the plasma.
The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study.
Measured: Days 1, 2, and 5 of Cycles 1 and 4
Area Under the Concentration-Time Curve (AUC) of Idasanutlin
AUC (from zero to infinity) represents the total drug exposure over time. The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study.
Measured: Days 1, 2, and 5 of Cycles 1 and 4
Half-life (t1/2) of Idasanutlin
t1/2 is defined as the time required for the drug plasma concentration to be reduced to half.
The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study.
Measured: Days 1, 2, and 5 of Cycles 1 and 4
Baseline and Mean Change From Baseline Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) Over Time
MPN-SAF Total Symptom Score is the sum of the following 10 items: early satiety, abdominal discomfort, inactivity, concentration issues, night sweats, Itching, Bone pain, Fever and Unintentional weight loss last 6 months and fatigue. The participant provides a severity score for each symptom on a scale of 0 as a minimum score (none/absent) to 10 (worst imaginable) as a maximum score.
Baseline (Cycle 1, Day 1) MPN-SAF total symptom score and the mean change from baseline score at each timepoint are reported. The change from baseline score was calculated by subtracting the post-baseline score from the baseline score.
The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the end of study.
Measured: Baseline (Cycle 1 Day 1), Cycle 2 Day 1, Days 28 of Cycles 3, 5, 8 (Week 32), 11, 14, 17 ) Day 28, Cycle 5 Day 28, End of Cycle 8 (Week 32), and Final Visit
Baseline and Mean Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores Over Time
Reported EORTC QLQ-C30 Scores include: Cognitive function, Diarrhea Emotional functioning, Nausea and vomiting, Social functioning, Physical functioning, Global health status/QoL and Role functioning. The questions use a 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale [1 'very poor' to 7 'Excellent']). Scores are averaged and transformed to 0-100 scale; higher score=better level of functioning or greater degree of symptoms.
The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the end of study.
Measured: Baseline (Cycle 1 Day 1), Cycle 2 Day 1, Cycles 3, 5, 8, 11, 14, 17, 20 Day 28 and Final Visit
Frequency Count of Participant Responses to the Patient Global Impression of Change (PGIC) Question Over Time
The PGIC is a one-item measure used to assess perceived treatment benefit. Participants were asked "Since the start of the treatment you've received in this study, your polycythemia vera (PV) symptoms are: 'very much improved', 'much improved', 'minimally improved', 'no change', 'minimally worse', 'much worse', and 'very much worse'.
The study was pre-maturely terminated by the sponsor's decision, therefore did not reach the end of study.
Measured: Cycle 2 Day 1, Cycle 3 Day 28, Cycle 5 Day 28, End of Cycle 8 (Week 32), and every 3 cycles thereafter (1 cycle is 28 days) until end of study (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 posted19 Sep 2017
- Study start21 Feb 2018
- Primary completion3 Mar 2020
- Study completion3 Mar 2020
Why it stopped: The Sponsor decided to discontinue the development of idasanutlin in the polycythemia vera indication.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Polycythemia VeraStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03287245
- Sponsor's protocol ID
- NP39761
- Other IDs
- 2017-000861-58, 2017
- Status last verified
- Dec 2021
- First submitted
- 8 Sep 2017
- Last updated
- 8 Dec 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Mascarenhas J, Passamonti F, Burbury K, El-Galaly TC, Gerds A, Gupta V, Higgins B, Wonde K, Jamois C, Kovic B, Huw LY, Katakam S, Maffioli M, Mesa R, Palmer J, Bellini M, Ross DM, Vannucchi AM, Yacoub A. The MDM2 antagonist idasanutlin in patients with polycythemia vera: results from a single-arm phase 2 study. Blood Adv. 2022 Feb 22;6(4):1162-1174. doi: 10.1182/bloodadvances.2021006043.
PubMed 34933330
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Single-Arm, Open-Label Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Idasanutlin Monotherapy in Patients With Hydroxyurea-Resistant/Intolerant Polycythemia Vera
- ClinicalTrials.gov ID
- NCT03287245
- Acronym / sponsor ID
- NP39761
- Conditions
- Polycythemia Vera
- Keywords
- polycythemia vera, PV, P vera, myeloproliferative diseases, hematologic diseases, myeloproliferative neoplasm, MPN
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The Sponsor decided to discontinue the development of idasanutlin in the polycythemia vera indication.
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 21 Feb 2018 (actual)
- Primary completion
- 3 Mar 2020 (actual)
- Study completion
- 3 Mar 2020 (actual)
- First posted
- 19 Sep 2017 (actual)
- Results
- Posted 27 May 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label, single-arm study of idasanutlin monotherapy in participants with hydroxyurea (HU)-resistant/intolerant Polycythemia vera (PV). The study will include two phases: initial phase and expansion phase. The initial phase will assess the safety and efficacy of idasanutlin monotherapy in ruxolitinib naïve and ruxolitinib-resistant or intolerant patients, respectively. If the initial phase shows promising results for ruxolitinib-resistant or intolerant patients, an expansion phase will be opened to further characterize the efficacy of idasanutlin.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Idasanutlin | Experimental | Drug: IdasanutlinTwo cohorts of ruxolitinib-naïve and ruxolitinib-resitant or intolerant participants will be enrolled to receive idasanutlin once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Documentation that the participant has met the revised 2016 World Health Organization (WHO) criteria for the diagnosis of polycythemia vera (PV)
- Hematocrit at screening and at initiation of idasanutlin greater than (>)40%
- Phlebotomy-dependent participants with splenomegaly by magnetic resonance imaging (MRI) or computerized tomography (CT) imaging (greater than or equal to [≥]450 cubic centimeters [cm^3]) or without splenomegaly (less than [<]450 cm^3 or prior splenectomy)
- Resistance to/intolerance to hydroxyurea according to modified European Leukemia Net (ELN) criteria
- For participants in the ruxolitinib intolerant or resistant group, in addition to previous hydroxyurea intolerance/resistance: Therapy-resistant PV after at least 6 months of treatment with ruxolitinib, as defined in the protocol; Ruxolitinib intolerance, as defined in the protocol; and Documentation of adverse events likely caused by ruxolitinib (assessment of attending physician) and that are of a severity that preclude further treatment with ruxolitinib (as per judgment of the attending physician and the patient)
Key exclusion criteria (15 listed)
- Meets the criteria for post-PV myelofibrosis as defined by the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT)
- Blast phase disease (>20% blasts in the marrow or peripheral blood)
- Clinically-significant thrombosis within 3 months of screening
- Participants who must receive CYP2C8 inhibitors, substrates and inducers, strong CYP3A4 inducers, or OATP1B1/3 substrates while on study. These must be discontinued 7 days (inhibitors and substrates) or 14 days (inducers) prior to start of study medication
- Previously treated with murine double minute 2 (MDM2) antagonist therapies or receiving interferon-alpha, anagrelide, or ruxolitinib within 28 days or 5 half-lives (whichever is shorter), or hydroxyurea within 1 day, or receiving any other cytoreductive or investigational agents within 28 days or 5 half-lives (whichever is shorter) of initial dose. Aspirin is permitted per treatment guidelines for PV unless medically contraindicated
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 |
|---|---|---|
| IdasanutlinAlso: RO5503781, RG7388All participants will receive 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Intra-participant dose-escalation to 200 mg daily for 5 days may be permitted after Cycle 3 for those who demonstrate no hematocrit (Hct) control and/or for those with inadequately controlled leukocytosis and/or thrombocytosis in which the investigator judges that better control is important. | Drug | Idasanutlin |
Primary outcome
Percentage of Ruxolitinib-Naïve Participants With Splenomegaly at Baseline Who Achieved Composite Response at Week 32
Time frame: Week 32
Composite response is defined as hematocrit (Hct) control without phlebotomy and ≥35% decrease in spleen size by imaging at Week 32. Hct control is defined as protocol-specified ineligibility for phlebotomy between Weeks 8 to 32 and ≤1 instance of phlebotomy eligibility between first dose and Week 8. Eligibility for phlebotomy is defined as a Hct of ≥45% that was ≥3% higher than baseline level or a Hct of >48%. One Cycle is 28 Days.
Percentage of Ruxolitinib-Naïve Participants Without Splenomegaly at Baseline Who Achieved Hematocrit (Hct) Control Without Phlebotomy at Week 32
Time frame: Week 32
Hct control is defined as protocol-specified ineligibility for phlebotomy between Weeks 8 to 32 and ≤1 instance of phlebotomy eligibility between first dose and Week 8. Eligibility for phlebotomy is defined as a Hct level ≥45% that was ≥3% higher than baseline level or a Hct level of >48%.
Percentage of All Ruxolitinib-Naïve Participants (Irrespective of Spleen Size) Who Achieved Hct Control Without Phlebotomy at Week 32
Time frame: Week 32
Hct control is defined as protocol-specified ineligibility for phlebotomy between Weeks 8 to 32 and ≤1 instance of phlebotomy eligibility between first dose and Week 8. Eligibility for phlebotomy is defined as a Hct level ≥45% that was ≥3% higher than baseline level or a Hct level of >48%.
Percentage of All Ruxolitinib-Resistant or Intolerant Participants Who Achieved Hct Control Without Phlebotomy at Week 32
Time frame: From Baseline to Week 32 (Cycle 8 Day 28)
Hct control is defined as protocol-specified ineligibility for phlebotomy between Weeks 8 to 32 and ≤1 instance of phlebotomy eligibility between first dose and Week 8. Eligibility for phlebotomy is defined as a Hct level ≥45% that was ≥3% higher than baseline level or a Hct level of >48%.
36 secondary outcomes
Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants Who Achieved Complete Hematologic Response at Week 32
Time frame: Week 32 (Cycle 8 Day 28)
Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants Who Achieved Complete Hematologic Remission at Cycle 11 Day 28
Time frame: Cycle 11 Day 28
Duration of Complete Hematologic Remission, With a Durable Responder Defined as a Participant in Remission at Week 32 and Cycle 11 Day 28
Time frame: Week 32 (Cycle 8 Day 28), Cycle 11 Day 28
Percentage of Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly at Baseline by Response Per Modified European Leukemia Net (ELN) Criteria
Time frame: Baseline, Day 28 of Cycles 3, 5, 8, 11, 12, 14, 17, 20 and Final visit (28 days after post-last dose)
Percentage of Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly at Baseline by Response Per Modified ELN Criteria
Time frame: Baseline, Day 28 of Cycles 3, 5, 8, 11, 12, 14, 17, 20 and Final visit (28 days after post-last dose)
Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants (Irrespective of Spleen Size) by Response Per Modified ELN Criteria
Time frame: Baseline, Day 28 of Cycles 3, 5, 8, 11, 12, 14, 17, 20 and Final visit (28 days after post-last dose)
Percentage of Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly at Baseline With Durable Response Lasting at Least 12 Weeks From Week 32
Time frame: From Week 32 (Cycle 8 Day 28) and at least 12 Weeks after until end of study (up to 2 years)
Number of Participants With a Durable Response, in Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly at Baseline With Durable Response Lasting at Least 12 Weeks From Week 32
Time frame: From Week 32 (Cycle 8 Day 28) and at least 12 weeks after until end of study (up to 2 years)
Percentage of Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly at Baseline With Durable Response Lasting at Least 12 Weeks From Week 32
Time frame: From Week 32 (Cycle 8 Day 28) and at least 12 Weeks after until end of study (up to 2 years)
Number of Participants With a Durable Response, in Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly at Baseline With Durable Response Lasting at Least 12 Weeks From Week 32
Time frame: From Week 32 (Cycle 8 Day 28) and at least 12 weeks after until end of study (up to 2 years)
Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants (Irrespective of Spleen Size) With Durable Response Lasting at Least 12 Weeks From Week 32
Time frame: From Week 32 (Cycle 8 Day 28) and at least 12 Weeks after until end of study (up to 2 years)
Number of Participants With a Duration Response, in All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants (Irrespective of Spleen Size) With Durable Response Lasting at Least 12 Weeks From Week 32
Time frame: From Week 32 (Cycle 8 Day 28) and at least 12 weeks after until end of study (up to 2 years)
Total Number of Participants With Adverse Events by Severity, Graded According to NCI CTCAE v4.0
Time frame: Baseline to end of study (up to 2 years)
Percentage of Participants With Clinical Laboratory Abnormalities: Hematology Parameters.
Time frame: Baseline to end of study (up to 2 years)
Percentage of Participants With Clinical Laboratory Abnormalities: Clinical Chemistry Parameters
Time frame: Baseline to end of study (up to 2 years)
Percentage of Participants With Clinical Laboratory Abnormalities: Urinalysis Parameters
Time frame: Baseline to end of study (up to 2 years)
Change From Baseline in Electrocardiogram Parameters: PQ(PR), QRS, QT, QTcB, QTcF, and RR Durations
Time frame: Baseline, Cycle 1 (Day 1, hours 4 and 6, Day 2 pre-dose and 24 Hour, Day 5 pre-dose, 4 and 6 Hour), Cycle 2 (Day 1 pre-dose only), Cycle 3 (Day 1 pre-dose, 4 and 6 Hour), Cycle 4 (Day 1 pre-dose and 4 Hour)
Change From Baseline in Heart Rate, as Measured by Electrocardiogram
Time frame: Baseline, Cycle 1 (Day 1, hours 4 and 6, Day 2 pre-dose and 24 Hour, Day 5 pre-dose, 4 and 6 Hour), Cycle 2 (Day 1 pre-dose only), Cycle 3 (Day 1 pre-dose, 4 and 6 Hour), Cycle 4 (Day 1 pre-dose and 4 Hour)
Change From Baseline in Oral Temperature
Time frame: Baseline, Cycle 1 (Days 15 and 22), Cycle 2 and 3 (Days 1 and 15), Each Cycle 4-23 (Day 1 only) and Final Visit
Change From Baseline in Pulse Rate
Time frame: Baseline, Cycle 1 (Days 15 and 22), Cycle 2 and 3 (Days 1 and 15), Each Cycle 4-23 (Day 1 only) and Final Visit
Change From Baseline in Respiratory Rate
Time frame: Baseline, Cycle 1 (Days 15 and 22), Cycle 2 and 3 (Days 1 and 15), Each Cycle 4-23 (Day 1 only) and Final Visit
Change From Baseline in Systolic Blood Pressure
Time frame: Baseline, Cycle 1 (Days 15 and 22), Cycle 2 and 3 (Days 1 and 15), Each Cycle 4-23 (Day 1 only) and Final Visit
Change From Baseline in Diastolic Blood Pressure
Time frame: Baseline, Cycle 1 (Days 15 and 22), Cycle 2 and 3 (Days 1 and 15), Each Cycle 4-23 (Day 1 only) and Final Visit
Eastern Cooperative Oncology Group (ECOG) Performance Status Over Time
Time frame: Baseline
Percentage of Participants With Concomitant Medications
Time frame: Overall Study Period
Maximum Serum Concentration Observed (Cmax) of Idasanutlin
Time frame: Days 1, 2, and 5 of Cycles 1 and 4
Trough Concentration (Ctrough) of Idasanutlin
Time frame: Days 1, 2, and 5 of Cycles 1 and 4
Time of Maximum Concentration Observed (Tmax) of Idasanutlin
Time frame: Days 1, 2, and 5 of Cycles 1 and 4
Clearance (CL) of Idasanutlin
Time frame: Days 1, 2, and 5 of Cycles 1 and 4
Apparent Clearance (CL/F) of Idasanutlin
Time frame: Days 1, 2, and 5 of Cycles 1 and 4
Volume or Apparent Volume of Distribution (Vdss/F) of Idasanutlin
Time frame: Days 1, 2, and 5 of Cycles 1 and 4
Area Under the Concentration-Time Curve (AUC) of Idasanutlin
Time frame: Days 1, 2, and 5 of Cycles 1 and 4
Half-life (t1/2) of Idasanutlin
Time frame: Days 1, 2, and 5 of Cycles 1 and 4
Baseline and Mean Change From Baseline Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) Over Time
Time frame: Baseline (Cycle 1 Day 1), Cycle 2 Day 1, Days 28 of Cycles 3, 5, 8 (Week 32), 11, 14, 17 ) Day 28, Cycle 5 Day 28, End of Cycle 8 (Week 32), and Final Visit
Baseline and Mean Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores Over Time
Time frame: Baseline (Cycle 1 Day 1), Cycle 2 Day 1, Cycles 3, 5, 8, 11, 14, 17, 20 Day 28 and Final Visit
Frequency Count of Participant Responses to the Patient Global Impression of Change (PGIC) Question Over Time
Time frame: Cycle 2 Day 1, Cycle 3 Day 28, Cycle 5 Day 28, End of Cycle 8 (Week 32), and every 3 cycles thereafter (1 cycle is 28 days) until end of study (up to 2 years)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Dec 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34933330Mascarenhas J, Passamonti F, Burbury K, El-Galaly TC, Gerds A, Gupta V, Higgins B, Wonde K, Jamois C, Kovic B, Huw LY, Katakam S, Maffioli M, Mesa R, Palmer J, Bellini M, Ross DM, Vannucchi AM, Yacoub A. The MDM2 antagonist idasanutlin in patients with polycythemia vera: results from a single-arm phase 2 study. Blood Adv. 2022 Feb 22;6(4):1162-1174. doi: 10.1182/bloodadvances.2021006043.
- Pioneeringhealthcare.com supports an online community of people impacted by Polycythemia Vera (PV, or P Vera), and provides explanations of medical terms and insights about the purpose of Roche's new clinical trial (NP39761) for patients with P Vera.Link provided by the sponsor.
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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.
Clinical Trials study director
Hoffmann-La Roche
11 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Idasanutlin in people with Polycythemia Vera, run by Hoffmann-La Roche at 11 sites in 4 countries.
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 11 inclusion and 15 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: stopped early, as of the sponsor's last update on 8 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, Italy, Australia, Canada. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Percentage of Ruxolitinib-Naïve Participants With Splenomegaly at Baseline Who Achieved Composite Response at Week 32 (time frame: Week 32). The study lists 4 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 NCT03287245, 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 8 Dec 2021.