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Trial record 1 of 15 for:    Idasanutlin
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A Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Idasanutlin Monotherapy in Participants With Hydroxyurea-Resistant/Intolerant Polycythemia Vera

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.
 
ClinicalTrials.gov Identifier: NCT03287245
Recruitment Status : Terminated (The Sponsor decided to discontinue the development of idasanutlin in the polycythemia vera indication.)
First Posted : September 19, 2017
Last Update Posted : April 3, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Polycythemia Vera Drug: Idasanutlin Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : February 21, 2018
Actual Primary Completion Date : March 3, 2020
Actual Study Completion Date : March 3, 2020


Arm Intervention/treatment
Experimental: Idasanutlin
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).
Drug: Idasanutlin
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.
Other Names:
  • RO5503781
  • RG7388




Primary Outcome Measures :
  1. Percentage of Ruxolitinib-Naïve Participants With Splenomegaly at Baseline who Achieved Composite Response at Week 32 [ Time Frame: From Baseline to Week 32 (Cycle 8 Day 28) ]
    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%.

  2. Percentage of Ruxolitinib-Naïve Participants Without Splenomegaly at Baseline who Achieved Hematocrit (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%.

  3. Percentage of All Ruxolitinib-Naïve Participants (Irrespective of Spleen Size) 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%.

  4. 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%.


Secondary Outcome Measures :
  1. Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants who Achieved Complete Hematologic Response at Week 32 [ Time Frame: From Baseline to Week 32 (Cycle 8 Day 28) ]
    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%.

  2. Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants who Achieved Complete Hematologic Remission at Cycle 11 Day 28 [ Time Frame: Baseline and from Week 32 (Cycle 8 Day 28) to Cycle 11 Day 28 (1 cycle is 28 days) ]
    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%.

  3. 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: Baseline, Week 32 (Cycle 8 Day 28), Cycle 11 Day 28, and every 3 cycles thereafter (1 cycle is 28 days) until end of study (up to 2 years) ]
    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%.

  4. 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, Cycle 3 Day 28, Cycle 5 Day 28, Cycle 8 Day 28 (Week 32), and every 3 cycles thereafter (1 cycle is 28 days) until end of study (up to 2 years) ]
    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.

  5. Percentage of Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly at Baseline by Response per Modified ELN Criteria [ Time Frame: Baseline, Cycle 3 Day 28, Cycle 5 Day 28, Cycle 8 Day 28 (Week 32), and every 3 cycles thereafter (1 cycle is 28 days) until end of study (up to 2 years) ]
    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.

  6. Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants (Irrespective of Spleen Size) by Response per Modified ELN Criteria [ Time Frame: Baseline, Cycle 3 Day 28, Cycle 5 Day 28, Cycle 8 Day 28 (Week 32), and every 3 cycles thereafter (1 cycle is 28 days) until end of study (up to 2 years) ]
    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.

  7. 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: Baseline, Cycle 3 Day 28, Cycle 5 Day 28, Week 32 (Cycle 8 Day 28), Cycle 11 Day 28, and every 3 cycles thereafter (1 cycle is 28 days) until end of study (up to 2 years) ]
    The percentage of participants with a durable response lasting at least 12 weeks from Week 32 will be analyzed by the type of response achieved: Hct control, complete hematologic response, ELN 2009 response criteria, and composite response, if applicable.

  8. Duration of 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: Baseline, Cycle 3 Day 28, Cycle 5 Day 28, Week 32 (Cycle 8 Day 28), Cycle 11 Day 28, and every 3 cycles thereafter (1 cycle is 28 days) until end of study (up to 2 years) ]
    The duration of response in participants with a durable response lasting at least 12 weeks from Week 32 will be analyzed by the type of response achieved: Hct control, complete hematologic response, ELN 2009 response criteria, and composite response, if applicable.

  9. 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: Baseline, Cycle 3 Day 28, Cycle 5 Day 28, Week 32 (Cycle 8 Day 28), Cycle 11 Day 28, and every 3 cycles thereafter (1 cycle is 28 days) until end of study (up to 2 years) ]
    The percentage of participants with a durable response lasting at least 12 weeks from Week 32 will be analyzed by the type of response achieved: Hct control, complete hematologic response, ELN 2009 response criteria, and composite response, if applicable.

  10. Duration of 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: Baseline, Cycle 3 Day 28, Cycle 5 Day 28, Week 32 (Cycle 8 Day 28), Cycle 11 Day 28, and every 3 cycles thereafter (1 cycle is 28 days) until end of study (up to 2 years) ]
    The duration of response in participants with a durable response lasting at least 12 weeks from Week 32 will be analyzed by the type of response achieved: Hct control, complete hematologic response, ELN 2009 response criteria, and composite response, if applicable.

  11. 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: Baseline, Cycle 3 Day 28, Cycle 5 Day 28, Week 32 (Cycle 8 Day 28), Cycle 11 Day 28, and every 3 cycles thereafter (1 cycle is 28 days) until end of study (up to 2 years) ]
    The percentage of participants with a durable response lasting at least 12 weeks from Week 32 will be analyzed by the type of response achieved: Hct control, complete hematologic response, ELN 2009 response criteria, and composite response, if applicable.

  12. Duration of 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: Baseline, Cycle 3 Day 28, Cycle 5 Day 28, Week 32 (Cycle 8 Day 28), Cycle 11 Day 28, and every 3 cycles thereafter (1 cycle is 28 days) until end of study (up to 2 years) ]
    The duration of response in participants with a durable response lasting at least 12 weeks from Week 32 will be analyzed by the type of response achieved: Hct control, complete hematologic response, ELN 2009 response criteria, and composite response, if applicable.

  13. Total Number of Participants With Adverse Events by Severity, Graded According to NCI CTCAE v4.0 [ Time Frame: From Baseline to end of study (up to 2 years) ]
    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.

  14. Percentage of Participants With Clinical Laboratory Abnormalities: Hematology Parameters [ Time Frame: From Baseline to end of study (up to 2 years) ]
    Hematology parameter laboratory values falling outside the standard reference range will be recorded as either high or low.

  15. Percentage of Participants With Clinical Laboratory Abnormalities: Clinical Chemistry Parameters [ Time Frame: From Baseline to end of study (up to 2 years) ]
    Clinical chemistry parameter laboratory values falling outside the standard reference range will be recorded as either high or low.

  16. Percentage of Participants With Clinical Laboratory Abnormalities: Urinalysis Parameters [ Time Frame: From Baseline to end of study (up to 2 years) ]
    Urinalysis parameter laboratory values falling outside the standard reference range will be recorded as either high or low.

  17. Change from Baseline in Electrocardiogram Parameters: PQ(PR), QRS, QT, QTcB, QTcF, and RR Durations [ Time Frame: Baseline, Cycle 1 Days 1, 2, and 5, Cycle 2 Day 1, Cycle 3 Day 1, and Day 1 of each cycle thereafter (1 cycle is 28 days) until end of study (up to 2 years) ]
  18. Change from Baseline in Heart Rate, as Measured by Electrocardiogram [ Time Frame: Baseline, Cycle 1 Days 1, 2, and 5, Cycle 2 Day 1, Cycle 3 Day 1, and Day 1 of each cycle thereafter (1 cycle is 28 days) until end of study (up to 2 years) ]
  19. Change from Baseline in Oral Temperature [ Time Frame: Baseline, Cycle 1 Days 1, 15, and 22, Days 1 and 15 of Cycles 2 and 3, and Day 1 of Cycle 4 and each cycle thereafter (1 cycle is 28 days) until end of study (up to 2 years) ]
  20. Change from Baseline in Pulse Rate [ Time Frame: Baseline, Cycle 1 Days 1, 15, and 22, Days 1 and 15 of Cycles 2 and 3, and Day 1 of Cycle 4 and each cycle thereafter (1 cycle is 28 days) until end of study (up to 2 years) ]
  21. Change from Baseline in Respiratory Rate [ Time Frame: Baseline, Cycle 1 Days 1, 15, and 22, Days 1 and 15 of Cycles 2 and 3, and Day 1 of Cycle 4 and each cycle thereafter (1 cycle is 28 days) until end of study (up to 2 years) ]
  22. Change from Baseline in Systolic Blood Pressure [ Time Frame: Baseline, Cycle 1 Days 1, 15, and 22, Days 1 and 15 of Cycles 2 and 3, and Day 1 of Cycle 4 and each cycle thereafter (1 cycle is 28 days) until end of study (up to 2 years) ]
  23. Change from Baseline in Diastolic Blood Pressure [ Time Frame: Baseline, Cycle 1 Days 1, 15, and 22, Days 1 and 15 of Cycles 2 and 3, and Day 1 of Cycle 4 and each cycle thereafter (1 cycle is 28 days) until end of study (up to 2 years) ]
  24. Eastern Cooperative Oncology Group (ECOG) Performance Status Over Time [ Time Frame: From Baseline to end of study (up to 2 years) ]
    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 (Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature), 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.

  25. Percentage of Participants With Concomitant Medications [ Time Frame: From Baseline to end of study (up to 2 years) ]
  26. Maximum Serum Concentration Observed (Cmax) of Idasanutlin [ Time Frame: Days 1, 2, and 5 of Cycles 1 and 4 ]
    Cmax is the maximum observed concentration of drug in blood.

  27. Trough Concentration (Ctrough) of Idasanutlin [ Time Frame: Days 1, 2, and 5 of Cycles 1 and 4 ]
    Ctrough is the measured concentration of a drug at the end of a dosing interval at steady state.

  28. Time of Maximum Concentration Observed (tmax) of Idasanutlin [ Time Frame: Days 1, 2, and 5 of Cycles 1 and 4 ]
    Tmax is the time elapsed from the time of drug administration to maximum plasma concentration.

  29. Clearance (CL) of Idasanutlin [ Time Frame: Days 1, 2, and 5 of Cycles 1 and 4 ]
    CL is a measure of the body's elimination of a drug from plasma over time.

  30. Apparent Clearance (CL/F) of Idasanutlin [ Time Frame: Days 1, 2, and 5 of Cycles 1 and 4 ]
    CL/F is a measure of the body's elimination of a drug from plasma over time, after oral administration.

  31. Volume or Apparent Volume of Distribution (Vdss/F) of Idasanutlin [ Time Frame: Days 1, 2, and 5 of Cycles 1 and 4 ]
    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.

  32. Area Under the Concentration-Time Curve (AUC) of Idasanutlin [ Time Frame: Days 1, 2, and 5 of Cycles 1 and 4 ]
    AUC (from zero to infinity) represents the total drug exposure over time.

  33. Half-life (t1/2) of Idasanutlin [ Time Frame: Days 1, 2, and 5 of Cycles 1 and 4 ]
    t1/2 is defined as the time required for the drug plasma concentration to be reduced to half.

  34. 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, 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) ]
    The MPN-SAF TSS is an assessment form to measure the severity of 9 clinically important symptoms of polycythemia vera. These include: early satiety, abdominal discomfort, inactivity, concentration issues, night sweats, itching, bone pain, fever, and weight loss. The participant provides a severity score for each additional symptom on a scale of 0 (none/absent) to 10 (worst imaginable). A tenth symptom, fatigue, is assessed using the "worst" fatigue item from the Brief Fatigue Inventory (BFI).

  35. 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, 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) ]
    EORTC QLQ-C30: includes functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most 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.

  36. 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) ]
    The PGIC is a one-item measure used to assess perceived treatment benefit. Participants will be 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'.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

  • 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
  • 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

Exclusion Criteria:

  • 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
  • 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

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 ClinicalTrials.gov identifier (NCT number): NCT03287245


Locations
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United States, Arizona
Mayo Clinic - Arizona
Phoenix, Arizona, United States, 85054
United States, Kansas
University of Kansas Cancer Center; Westwood Cancer Center/BMT Output Clinic
Kansas City, Kansas, United States, 66205
United States, New York
Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029
United States, Ohio
Cleveland Clinic Cancer Center
Independence, Ohio, United States, 44131
United States, Texas
University of Texas Health Sciences Center in San Antonio
San Antonio, Texas, United States, 78229
Australia, South Australia
Royal Adelaide Hospital; Haematology Clinical Trials
Adelaide, South Australia, Australia, 5000
Australia, Victoria
Peter MacCallum Cancer Centre; Department of Haematology
Melbourne, Victoria, Australia, 3002
Canada, Ontario
Princess Margaret Hospital; Department of Med Oncology
Toronto, Ontario, Canada, M5G 2M9
Italy
ASST PAPA GIOVANNI XXIII; Ematologia
Bergamo, Lombardia, Italy, 24127
Ospedale Di Circolo E Fondazione Macchi; Ematologia
Varese, Lombardia, Italy, 21100
Az. Ospedaliero-Universitaria Careggi; CRIMM
Firenze, Toscana, Italy, 50134
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
Additional Information:
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03287245    
Other Study ID Numbers: NP39761
2017-000861-58 ( EudraCT Number )
First Posted: September 19, 2017    Key Record Dates
Last Update Posted: April 3, 2020
Last Verified: April 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hoffmann-La Roche:
polycythemia vera
PV
P vera
myeloproliferative diseases
hematologic diseases
myeloproliferative neoplasm
MPN
Additional relevant MeSH terms:
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Polycythemia Vera
Polycythemia
Hematologic Diseases
Bone Marrow Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Neoplasms
Bone Marrow Diseases
Myeloproliferative Disorders