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MyelofibrosisPhase 1NCT02493530

TGR-1202 + Ruxolitinib PMF PPV-MF PET-MF MDS/MPN Polycythemia Vera Resistant to Hydroxyurea

A Phase 1 study testing TGR-1202 and ruxolitinib in people with Myelofibrosis and Polycythemia Vera, run by Vanderbilt-Ingram Cancer Center at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a Phase 1, open-label, study of TGR-1202, a PI3K delta inhibitor, administered together with ruxolitinib in patients with myeloproliferative neoplasms (specifically: polycythemia vera, primary myelofibrosis, PPV-MF or PET-MF) and MDS/MPN. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Myelofibrosis, Polycythemia Vera
What is being tested?
TGR-1202 and ruxolitinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
5 sitesUnited States
Study dates
Jul 2015to May 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Must voluntarily sign an ICF; and must be able to meet all study requirements
  • For escalation, subjects must have a pathologically confirmed diagnosis of PPV-MF, PETMF, or PMF as per the EHA or WHO diagnostic criteria (note that all diagnoses must include the presence of at least Grade 1 marrow fibrosis according to the European Consensus on Grading of BM Fibrosis as well as int-1, int-2, or high risk disease according to the IWG-MRT Dynamic IPSS; Patients with PV may enter the trial if they meet the labeled indication for ruxolitinib (eg hydroxyurea resistant or refractory);
  • Escalation Stage 1 patients: who have not achieved normalization of splenomegaly, symptomology, or blood counts with at least 8 weeks therapy with a steady dose of ruxolitinib
  • Escalation Stage 2: patients who have not yet received therapy with any JAK-STAT inhibitory agents or patients on at least 8 weeks of a steady dose of ruxolitinib; patients with exposure to other JAK-STAT inhibitory agents are not eligible. After discussion with the study chair or designee, patients with suboptimal response on at least 8 weeks of a steady dose of ruxolitinib may be allowed to de-escalate ruxolitinib therapy in order to enter a safety cohort which is enrolling patients at a lower dose; patients must receive the lower dose of ruxolitinib for at least 7 consecutive days without event before adding TGR-1202. If the patient completed screening evaluations including bone marrow biopsy/aspirate prior to ruxolitinib de-escalation, it need not be repeated after de-escalation provided that all evaluations occurred within 28 days prior to the first dose of TGR-1202.
  • For expansion,
  • subjects may have a pathologically confirmed diagnosis of MF or PV as noted above in #2. There are also two expansion cohorts for patients with MDS/MPN (CMML, aCML, RARS-T or MDS/MPN-U) which warrants treatment. Patients with these diagnoses may be eligible, provided they are able to obtain ruxolitinib from commercial supply.
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  • patients who have not yet received therapy with any JAK-STAT inhibitory agents or patients on at least 8 weeks of a steady dose of ruxolitinib; patients with exposure to other JAK-STAT inhibitory agents are not eligible.
  • A bone marrow biopsy must be performed within four weeks prior to Cycle 1 Day 1 treatment to establish the baseline fibrosis score, and consent is required prior to that bone marrow biopsy to assure tissue is collected for protocol mandated testing;
  • Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2;
  • Life expectancy of at least six months;
  • Recovery to ≤ Grade 1 or baseline of any toxicities due to prior systemic treatments, excluding alopecia and anemia/thrombocytopenia assessed to be related to Ruxolitinib exposure;
  • Women of child bearing potential (WCBP), defined as a sexually mature woman not surgically sterilized or not post-menopausal for at least 24 consecutive months if ≤55 years or 12 months if >55 years, must have a negative serum pregnancy test within 72 hours prior to the first dose of study drug and must agree to use highly effective methods of birth control throughout the study. Highly effective methods of contraception include total abstinence, sterilization of patient and/or patient's partner, or use of combination of two methods, including barrier methods (double barrier method is acceptable), IUD or IUS, and hormonal implants or combined oral contraceptives
  • Must have adequate organ function as demonstrated by the following:
  • ALT (SGPT) and/or AST (SGOT) ≤ 3x upper limit of normal (ULN), or ≤ 4 x ULN (if upon judgment of the treating physician, it is believed to be due to extramedullary hematopoiesis [EMH] related to MF); Total bilirubin ≤ 1.5 x ULN; or ≤ 2x ULN (if upon judgment of the treating physician, it is believed to be due to EMH related to MF); Serum creatinine ≤ 2.5 mg/dL x ULN; Hgb ≥ 8 g/dL; Plt ≥ 30k; ANC ≥ 750/uL

Who cannot join

  • Patients who meet any of the following criteria will be excluded from trial entry:
  • Other invasive malignancies within the last 2 years, except non-melanoma skin cancer and localized cured prostate, cervical cancer, and DCIS
  • History of cerebral vascular accident, unstable angina, myocardial infarction, or ventricular arrhythmia within the last 6 months;
  • Any serious, unstable medical or psychiatric condition that would prevent, (as judged by the Investigator) the subject properly providing informed consent or any condition which would jeopardize compliance with the protocol
  • Known history of human immunodeficiency virus (HIV), or known active hepatitis A, B, or C infection (hepatitis B carriers with normal LFTs and undetectable viral loads are allowed);
  • Organ transplant recipients other than bone marrow transplant;
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  • Women who are pregnant or lactating;
  • Autologous hematologic stem cell transplant within 3 months of study entry. Allogeneic stem cell transplant within 6 months. Grade II, or greater, active graft versus-host disease.
  • Use of an investigational drug within 21 days or 5 half-lives (whichever is shorter) prior to the first dose of TGR-1202. For investigational drugs for which 5 half-lives is less than 21 days, a minimum of 10 days between termination of the investigational drug and administration of TGR-1202 is required.
  • Previous therapy with GS-1101 (CAL-101), IPI-145 or any drug that specifically inhibits PI3K or mTOR within last 6 months;
  • Any major surgery, chemotherapy, or immunotherapy within the last 21 days (limited palliative radiation is allowed ≥ 2 weeks); concurrent hydroxyurea is allowed if less than 2 grams daily and on stable dose for ≥14 days prior to study entry;
  • Patient has received wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) ≤ 28 days or limited field radiation for palliation ≤ 14 days prior to starting trial medications or has not recovered from side effects of such therapy;
  • Ongoing immunosuppressive therapy (prednisone or equivalent ≤10 mg daily allowed as clinically warranted). Patients are allowed to use topical or inhaled corticosteroids;
  • Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol
  • Concurrent condition that in the investigator's opinion would jeopardize compliance with the protocol.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • University of Colorado Cancer Center

    Aurora, Colorado, 80045

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Vanderbilt-Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Mayo Clinic - Arizona

    Phoenix, Arizona, 85054

  • Mays Cancer Center at University of Texas Health San Antonio

    San Antonio, Texas, 78229

Other trials in United States

About this study

Official title: A Phase 1 Dose Escalation and Expansion Study of TGR-1202 + Ruxolitinib in Subjects With Primary Myelofibrosis (PMF), Post-Polycythemia Vera MF (PPV-MF), Post-Essential Thrombocythemia MF (PET-MF), MDS/MPN, or Polycythemia Vera Resistant to Hydroxyurea

This is a Phase 1, open-label, study of TGR-1202, a PI3K delta inhibitor, administered together with ruxolitinib in patients with myeloproliferative neoplasms (specifically: polycythemia vera, primary myelofibrosis, PPV-MF or PET-MF) and MDS/MPN.

Read the detailed description

The escalation will include 2 initial sequential stages. Stage 1 will include myelofibrosis or hydroxyurea-resistant/refractory PV patients already taking therapeutic levels of ruxolitinib, but who are not achieving maximal response at the highest tolerated dose of ruxolitinib as discussed among investigators. Only TGR-1202 will be escalated in a modified 3+3 dose escalation algorithm to determine the MTD of TGR-1202 to be given with any given dose of ruxolitinib.

Stage 2 will include myelofibrosis or hydroxyurea-resistant/refractory PV patients who have never been on JAK-STAT inhibitory agents, and includes simultaneously initiation of both ruxolitinib and TGR-1202. In Stage 2, JAK Inhibitor naïve patients will receive TGR-1202 at the recommended dose established in Cohort 1, and ruxolitinib. As patients in Stage 1 will be on ruxolitinib at different doses, dose levels in Stage 2 will expand to meet requirements for safety analysis.

Being tested
TGR-1202, ruxolitinib
Keywords
MDS/MPN
Medical subject headings
Primary Myelofibrosis, Polycythemia Vera

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TGR-1202Drug

    Stage 1 will include myelofibrosis or hydroxyurea-resistant/refractory PV patients already taking therapeutic levels of ruxolitinib, but who are not achieving maximal response at highest tolerated dose of ruxolitinib.

    Stage 2 will include myelofibrosis or hydroxyurea-resistant/refractory PV patients who have never been on JAK-STAT inhibitory agents, and includes simultaneously initiation of both ruxolitinib and TGR-1202. TGR-1202 will be administered at or below the recommended dose established in Stage 1.

    Expansion will commence after proper combination doses of both agents is established.

  • ruxolitinibDrug

    Also called Jakafi

Study groups in NCT02493530
Study groupRoleWhat they receive
Escalation and expansionExperimentalTGR1202 and Ruxolitinib combination
Receives: Drug: TGR-1202; Drug: ruxolitinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety of TGR1202 in combination with ruxolitinib

    All patients who have received at least one dose of TGR-1202 will be included in the safety population. All clinical safety data (vital signs, routine laboratory tests, and adverse events) will be tabulated and listed. The safety and tolerability of TGR-1202 and ruxolitinib will be evaluated by means of drug-related dose limiting toxicity, adverse event (AE) reports, physical examinations and laboratory safety evaluations.

    Measured: </=12 months

Secondary outcomes (3)

  1. Overall response

    Number of patients in each response category, polycythemia IWG response criteria, IWG-MRT response criteria, IWG MDS/MPN response criteria summarized as follows for target lesion criteria (see IWG for additional details): complete response (CR), normalization of bone marrow, peripheral counts, spleen size, and symptoms; partial response (PR); Hematologic improvement (HI), or progressive disease (PD). Patients are categorized according to the best response achieved prior to occurrence of progressive disease, where best response hierarchy is CR>PR>HI>SD>PD.

    Measured: EOT - 12 months

  2. Total symptom score (MPN-TSS)

    The myeloproliferative neoplasm - total symptoms score (MPN-TSS) is a validated tool in measurement in symptoms for patients with these diseases and we will measure patient reported outcomes with this validated tool

    Measured: 16 weeks of therapy

  3. Blood levels of TGR1202 in combination with ruxolitinib (Pharmacokinetics)

    The PK parameters (including AUC (0-∞), AUC (0- τ), Cmax, tmax, λz, and t½) of TGR-1202 and ruxolitinib following will be assessed by analysis of TGR-1202 plasma concentrations during the dose escalation phase of the study.

    Measured: 30 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Jul 2015 (estimated)
  2. Study startJul 2015
  3. Primary completion21 Mar 2023
  4. Study completionMay 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02493530
Sponsor's protocol ID
VICC HEM 1538
Status last verified
Aug 2025
First submitted
1 Jul 2015
Last updated
19 May 2026
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing TGR-1202 and ruxolitinib in people with Myelofibrosis and Polycythemia Vera, run by Vanderbilt-Ingram Cancer Center at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 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: finished, as of the sponsor's last update on 19 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Safety of TGR1202 in combination with ruxolitinib (time frame: </=12 months). 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 NCT02493530.

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 19 May 2026.

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