Open Label Study of Single Agent Oral RG7388 in Patients With Polycythemia Vera and Essential Thrombocythemia
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|ClinicalTrials.gov Identifier: NCT02407080|
Recruitment Status : Completed
First Posted : April 2, 2015
Last Update Posted : September 12, 2019
This research looks at two conditions, Essential Thrombocythemia (ET) and Polycythemia Vera (PV). ET causes people to produce too many blood cells called platelets and PV causes too many platelets and red blood cells to be made. Platelets are particles which circulate in the blood stream and normally prevent bleeding and bruising. Having too many platelets in the blood increases the risk of developing blood clots, which can result in life threatening events like heart attacks and strokes. When the number of red blood cells is increased in PV this will slow the speed of blood flow in the body and increase the risk of developing blood clots.
The purpose of Part A of this study is to test the safety and tolerability of drug RG7388 patients and identify the recommended phase II dose in a single agent dose escalation study. The investigators want to find out what effects, good and/or bad it has on the disease.
The purpose of Part B of this study is to test the safety and tolerability of the combination of RG7388 and Pegylated Interferon Alfa-2a or Pegasys in PV/ET patients from Part A who did not achieve at least a partial response by the end of three cycles of single agent RG7388.
Essential Thrombocythemia (ET) and Polycythemia Vera (PV) have been difficult diseases to treat. RG7388 is a selective inhibitor of the p53-MDM2 binding that frees p53 from negative control and activates the p53 pathway in cancer cells, leading to cell cycle arrest and apoptosis in vitro and in vivo. It has been used to treat solid tumors and Acute Myelogenous Leukemia (AML) in clinical trials. Pegasys is a drug that is the standard of care for patients who have Chronic Hepatitis B (CHB).
RG7388 is a drug that is not yet approved by the Federal Drug Administration (FDA) for the treatment of patients with essential thrombocythemia or polycythemia vera. Pegasys is a drug that is approved by the FDA for the treatment of CHB. The use of RG7388 alone and in combination with Pegasys is experimental.
|Condition or disease||Intervention/treatment||Phase|
|Polycythemia Vera Essential Thrombocythemia||Drug: RG7388 Drug: Pegasys||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||13 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Open Label Phase I Study of Single Agent Oral RG7388 in Patients With Polycythemia Vera and Essential Thrombocythemia (With Pilot Feasibility Study in Combination With Pegylated Interferon Alfa 2a for Patients Who do Not Respond to the Single Agent at Each Dose Level)|
|Study Start Date :||April 2015|
|Actual Primary Completion Date :||December 19, 2018|
|Actual Study Completion Date :||December 19, 2018|
Part A: RG7388 as a single agent; given at a starting dose of 100 mg each day for five days for the first cycle which will be 56 days.
Part B: combination of RG7388 and Pegasys if subject does not achieve at least a PR by the end of 3 cycles of single agent RG7388
RG7388 is supplied as film-coated tablets at dosage strengths of 50 mg, 200 mg, 300mg and 400 mg.
PEGASYS is supplied as a clear, sterile solution for subcutaneous (SQ) injection available in prefilled syringes. weekly doses at 45ug subcutaneously
Other Name: pegylated interferon alfa-2a
- The dose limiting toxicity of RG7388 [ Time Frame: up to 56 days ]
- The dose limiting toxicity of combination of RG7388 and Pegasys [ Time Frame: up to 2 years ]
- Hematologic response of PR + CR by modified ELN response criteria [ Time Frame: up to 2 years ]
- Molecular response by percent reduction in baseline JAK2V617F allele burden [ Time Frame: up to 2 years ]
- Changes in bone marrow histopathologic abnormalities [ Time Frame: up to 2 years ]
- Reduction in baseline reticulin/collagen fibrosis [ Time Frame: up to 2 years ]
- Incidence of venous and arterial thrombosis [ Time Frame: up to 2 years ]
- Changes in MPN related symptoms as measured by the MPN-SAF [ Time Frame: up to 2 years ]
- Pre-treatment wild type P53 status and MDM2 levels as predictors of response to therapy [ Time Frame: baseline ]
- Changes in mRNA levels of the following biomarkers : • MIC-1, PCNA, CDKN1A/p21, GDF15, TNFRSF10B/TRAIL-R2, TP53I3/PIG3, and GADD45 [ Time Frame: baseline and 2 years ]
- Pre-treatment wild type P53 status and MDM2 levels as predictors of response to combination therapy who failed RG7388 alone and were subsequently treated with combination therapy [ Time Frame: baseline ]
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): NCT02407080
|United States, District of Columbia|
|Georgetown University Medical Center|
|Washington, District of Columbia, United States, 20007|
|United States, New York|
|Icahn School of Medicine at Mount Sinai|
|New York, New York, United States, 10029|
|United States, North Carolina|
|Wake Forest University Baptist Medical Center|
|Winston-Salem, North Carolina, United States, 27157|
|Study Chair:||John Mascarenhas, MD||Icahn School of Medicine at Mount Sinai|
|Study Chair:||Ronald Hoffman, MD||Icahn School of Medicine at Mount Sinai|