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Primary MyelofibrosisPhase 2NCT01790295

Ruxolitinib Prior to Transplant in Patients With Myelofibrosis

A Phase 2 study testing Ruxolitinib Pre- Hematopoietic cell transplantation (HCT) in people with Primary Myelofibrosis and Post Polycythemia Vera Myelofibrosis, run by John Mascarenhas at 8 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The purpose of this study is to find out if giving the study drug Ruxolitinib (INC424) prior to a combination of other chemotherapeutic drugs (Fludarabine and Busulfan) before infusing another person's hematopoietic stem cells (bone marrow transplantation) will be successful in people who have advanced primary… Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
Ruxolitinib Pre- Hematopoietic cell transplantation (HCT)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
8 sitesin 3 countries
Study dates
Nov 2013to 26 Oct 2017
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 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Documented diagnosis of primary myelofibrosis according to WHO criteria or post PV myelofibrosis or post ET myelofibrosis as per IWG-MRT criteria
  • Age 18-70 years
  • Intermediate-2/ high-risk disease as per Dynamic IPSS (DIPSS) criteria OR Intermediate-1 risk disease with one of the following additional unfavorable features known to impact the survival adversely
  • Red cell transfusion dependency
  • Unfavorable Karyotype
  • Platelet count <100 x 109/l
Show all 19Show fewer
  • Blasts in the PB and BM ≤10% prior to study enrollment
  • Availability of a suitable matched related (6/6 or 5/6) or unrelated donor (10/10 or 9/10 antigen or allele matched).
  • Able to give informed written consent
  • ECOG Performance status of 0-2.
  • Life expectancy >3 months
  • Off all MF-directed therapy including investigational agents for at least 2 weeks prior to study enrollment and recovered from all toxicities*
  • Adequate organ function
  • Adequate renal function - creatinine <1.5 x IULN
  • Adequate hepatic function - AST/ALT <2.5 x IULN, Total Bilirubin <1.5 x IULN
  • Adequate hematopoietic function - Platelet ≥50 x 109/l and ANC ≥1.0 x 109/l
  • LVEF >40% (MUGA or echocardiogram) Normal per Institutional standard
  • Adequate pulmonary function with DLCO >50%
  • A patient who has been on stable dose of Ruxolitinib and has received ruxolitinib ≤6 months prior to the study entry will be considered potentially eligible for the study with the caveat that there is no evidence of loss of response (>5cm increase in spleen size from the nadir).

Who cannot join

  • Any previous JAK2 inhibitor treatment prior to study enrollment, with the exception of Ruxolitinib
  • Hypersensitivity to JAK inhibitor
  • Clinical or laboratory evidence of cirrhosis
  • Prior allogeneic transplant for any hematopoietic disorder
  • >20% blast in the PB or BM prior to HCT or had leukemic transformation (>20% blasts in PB or BM any time prior to HCT)
  • Syngeneic donor
Show all 15Show fewer
  • Cord Blood transplant
  • Active uncontrolled infection
  • H/o another malignancy within 5-years of date of HCT except h/o basal cell or squamous cell carcinoma of skin or PV or ET
  • Known HIV positive
  • Pregnancy at the time of BMT
  • Any other concurrent illness which in investigator's opinion puts the patient at excessive risk of treatment related toxicities
  • Unable to give informed consent
  • Active infection with hepatitis A,B or C virus
  • Subjects who require therapy with a strong CYP3A4 inhibitor prior to enrollment to this study

Trial locations and contacts

8 sites in 3 countries.

8 sites in 3 countries

United States6 sites
  • Emory Hospital

    Atlanta, Georgia, 30322

  • Northwestern University, Robert h. Lurie Comprehensive Cancer Center

    Chicago, Illinois, 60611

  • Ohio State University

    Columbus, Ohio, 43210

  • Icahn School of Medicine at Mount Sinai

    New York, New York, 10029

  • University of Kansas Cancer Center

    Westwood, Kansas, 66205

  • Wake Forest Baptist Medical Center

    Winston-Salem, North Carolina, 27103

Other trials in United States

Canada1 site
  • Princess Margaret Cancer Centre, University of Toronto

    Toronto, M5G 2M9

Other trials in Canada

United Kingdom1 site
  • University of Oxford

    Oxford, OX3 9DS

Other trials in United Kingdom

About this study

Official title: Exploring the Potential of Dual Kinase JAK 1/2 Inhibitor Ruxolitinib (INC424) With Reduced Intensity Allogeneic Hematopoietic Cell Transplantation in Patients With Myelofibrosis

The purpose of this study is to find out if giving the study drug Ruxolitinib (INC424) prior to a combination of other chemotherapeutic drugs (Fludarabine and Busulfan) before infusing another person's hematopoietic stem cells (bone marrow transplantation) will be successful in people who have advanced primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF) or post-essential thrombocythemia myelofibrosis (PET-MF), collectively known as myelofibrosis (MF). MF is a disorder in which bone marrow tissue develops in abnormal sites because the bone marrow itself undergoes fibrosis or scarring. This study plans to evaluate whether adding the drug Ruxolitinib will further aid in reducing pre-transplant spleen size, improve physical performance levels and reduce adverse events (side effects) related to the transplant. Ruxolitinib is a drug that is approved by the FDA for the treatment of patients with advanced forms of myelofibrosis. Using Ruxolitinib prior to stem cell transplantation is experimental.

Read the detailed description

A two- stage Simon Phase II study will be conducted in each of two groups of patients: related and unrelated donor transplants. In each donor transplant group, the first stage of this design will include 11 patients evaluated for death or graft failure by 100 days post-transplant. In each stratum, we will enroll additional patients (up to 20%) of stratum total to take into account exclusions due to donor failure (such as donor deemed unsuitable for stem cell donation due to medical or other reasons) only. Those patients who have toxicities related to Ruxolitinib and not been able to reach HCT due to these toxicities will be included in the estimation of overall failure rates. Only those patients who are excluded based on donor related issues without any regimen related complications will be excluded from the estimation of failure rates. However, all data on these patients will be reported.

Being tested
Ruxolitinib Pre- Hematopoietic cell transplantation (HCT)
Keywords
Myelofibrosis, Stem cell transplant, Ruxolitinib
Medical subject headings
Primary Myelofibrosis

What participants receive

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

  • Ruxolitinib Pre- Hematopoietic cell transplantation (HCT)Drug

    Also called Ruxolitinib \Pre- Hematopoietic cell transplantation (HCT), INC424

    Ruxolitinib (INC424) tablets will be started 60 days (day -65) prior to start of conditioning chemotherapy. The starting dose of Ruxolitinib will be determined according to baseline platelet count and will be modified according to platelet count at follow-up. The drug will be given in the maximum tolerated dose as defined in the protocol for 56 days, followed by 4 days of taper, and will be stopped completely at the planned start of conditioning therapy (starting on day -5) i.e. 5 days prior to stem cell infusion. The drug will be supplied as 5 mg tablets.

Study groups in NCT01790295
Study groupRoleWhat they receive
Ruxolitinib Pre- Hematopoietic cell transplantation (HCT)ExperimentalRuxolitinib (INC424) tablets will be started 62 days (day -67) prior to start of conditioning chemotherapy. The starting dose of Ruxolitinib will be determined according to baseline platelet count and will be modified according to platelet count at follow-up. The drug will be given in the maximum tolerated dose as defined in the protocol for 56 days, followed by 4 days of taper, and will be stopped completely at the planned start of conditioning therapy (starting on day -5) i.e. 5 days prior to stem cell infusion. The drug will be supplied as 5 mg tablets.
Receives: Drug: Ruxolitinib Pre- Hematopoietic cell transplantation (HCT)

What is being measured

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

  1. Percent of Participants With 100-day Survival Without Graft Failure

    The feasibility of combining Ruxolitinib (INC424) with a Reduced intensity conditioning (RIC) regimen likely to produce success post transplantation, success being defined as patient being alive, and without graft failure at day 100-post allogeneic stem cell transplantation (in patients who receive (a) related donor transplant and in those who receive (b) an unrelated donor transplant.

    Measured: Day 100-post allogeneic stem cell transplantation

Secondary outcomes (19)
  1. Time to Neutrophil Recovery

    Neutrophil recovery will be defined as first of the three consecutive days with neutrophil count ≥0.5 x 109/l.

    Measured: up to 4 years

  2. Platelet Recovery

    Platelet recovery will be defined as first of the 7 days with platelet count ≥20 x 109/l, without platelet transfusion support and both maintained for 30 days without transfusion support or myeloid cytokine support.

    Measured: up to 4 years

  3. Percent of Participants With Non-relapse Mortality (NRM)

    NRM will be defined as death in first 30 days due to any cause, and subsequently death due to any cause without the recurrence or progression of myelofibrosis. Cumulative incidence of NRM will be calculated taking relapse/progression as competing event.

    Measured: 100 days

  4. Percent of Participants With Non-relapse Mortality (NRM)

    NRM will be defined as death in first 30 days due to any cause, and subsequently death due to any cause without the recurrence or progression of myelofibrosis. Cumulative incidence of NRM will be calculated taking relapse/progression as competing event.

    Measured: 1-year post transplant

  5. Percent of Participants With Graft Versus Host Disease (GvHD)

    Acute and chronic GvHD. GvHD is a potentially serious complication of allogeneic stem cell transplantation.

    Stage Skin Liver (bilirubin) Gut (stool output/day)

    0 No GVHD rash < 2 mg/dl < 500 ml/day or persistent nausea.

    1. Maculopapular rash< 25% body surface area (BSA) 2-3 mg/dl 500-999 ml/day
    2. Maculopapular rash 25 - 50% BSA 3.1-6 mg/dl 1000-1500 ml/day
    3. Maculopapular rash > 50% BSA 6.1-15 mg/dl Adult: >1500 ml/day
    4. Generalized erythroderma plus bullous formation >15 mg/dl Severe abdominal pain with or without ileus Grade I Stage 1-2 None None II Stage 3 or Stage 1 or Stage 1 III - Stage 2-3 or Stage 2-4 IV Stage 4 or Stage 4 -

    Measured: 1-year post transplant

  6. Chimerism Studies

    Will check percentage of donor versus recipient blood cells to determine efficacy of donor engraftment

    Measured: 30 days post transplant

  7. Chimerism Studies

    Will check percentage of donor versus recipient blood cells to determine efficacy of donor engraftment

    Measured: 60 days post transplant

  8. Chimerism Studies

    Will check percentage of donor versus recipient blood cells to determine efficacy of donor engraftment

    Measured: 100 days post transplant

  9. Number of Participants With Remission Status According to IWG-MRT Criteria

    Remission status according to International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) criteria

    Remission defined as:

    Bone marrow:* Age-adjusted normocellularity; <5% blasts; ≤grade 1 MF and Peripheral blood: Hemoglobin ≥100 g/L and <UNL; neutrophil count ≥ 1 × 109/L and <UNL; Platelet count ≥100 × 109/L and <UNL; <2% immature myeloid cells and Clinical: Resolution of disease symptoms; spleen and liver not palpable; no evidence of extramedullary hematopoiesis (EMH)

    Measured: Day 100 post transplant

  10. Number of Participants With Remission Status at 6 Months Post Transplant

    Remission defined as:

    Bone marrow:* Age-adjusted normocellularity; <5% blasts; ≤grade 1 MF† and Peripheral blood: Hemoglobin ≥100 g/L and <UNL; neutrophil count ≥ 1 × 109/L and <UNL; Platelet count ≥100 × 109/L and <UNL; <2% immature myeloid cells‡ and Clinical: Resolution of disease symptoms; spleen and liver not palpable; no evidence of EMH

    Measured: 6 months post transplant

  11. Number of Participants With Remission Status at 12 Months Post Transplant

    Remission defined as:

    Bone marrow:* Age-adjusted normocellularity; <5% blasts; ≤grade 1 MF† and Peripheral blood: Hemoglobin ≥100 g/L and <UNL; neutrophil count ≥ 1 × 109/L and <UNL; Platelet count ≥100 × 109/L and <UNL; <2% immature myeloid cells‡ and Clinical: Resolution of disease symptoms; spleen and liver not palpable; no evidence of EMH

    Measured: 12 months post transplant

  12. Number of Participants With Relapse/Progression (Defined as Per IWG-MRT Criteria)

    Relapse/progression defined as:

    Peripheral blood: Hemoglobin ≥100 g/L and <UNL; neutrophil count ≥1 × 109/L and <UNL; platelet count ≥100 × 109/L and <UNL; <2% immature myeloid cells‡ and Clinical: Resolution of disease symptoms; spleen and liver not palpable; no evidence of EMH or Bone marrow:* Age-adjusted normocellularity; <5% blasts; ≤grade 1 MF†, and peripheral blood: Hemoglobin ≥85 but <100 g/L and <UNL; neutrophil count ≥1 × 109/L and <UNL; platelet count ≥50, but <100 × 109/L and <UNL; <2% immature myeloid cells‡ and Clinical: Resolution of disease symptoms; spleen and liver not palpable; no evidence of EMH

    Measured: 1-year post transplant

  13. Number of Participants With Progression-free Survival

    Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

    Measured: 1-year post transplant

  14. Number of Overall Survival

    Measured: 1-year post transplant

  15. Mean Change in the Brief Fatigue Inventory Score

    Mean change in the Brief Fatigue Inventory score (BFI) from baseline to 48 months to assess impact of allogeneic stem cell transplant on myelofibrosis associated symptoms and overall quality of life. The BFI is a 9 item scored from 0 (no fatigue) -10 (as bad as you can imagine), items are averaged with total score from 0-10, with higher score indicating more fatigue.

    Measured: baseline and 48 months

  16. Expression Profiling and Measurements of Cytokines Prior to Start of Ruxolitinib, Prior to Start of Chemotherapy for Conditioning

    Measured: 30 days post transplant

  17. Expression Profiling and Measurements of Cytokines Prior to Start of Ruxolitinib, Prior to Start of Chemotherapy for Conditioning

    Measured: 100 days post transplant

  18. Association of Cytokines Levels With Acute and Chronic GvHD

    Measured: 30 days post transplant

  19. Association of Cytokines Levels With Acute and Chronic GvHD

    Measured: 100 days post transplant

Timeline

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

  1. First posted13 Feb 2013 (estimated)
  2. Study startNov 2013
  3. Primary completion26 Oct 2017
  4. Study completion26 Oct 2017

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01790295
Sponsor's protocol ID
GCO 12-1809
Other IDs
MPD-RC 114
Status last verified
Feb 2019
First submitted
8 Feb 2013
Last updated
20 Mar 2019
Data monitoring committee
Yes

Publications

  • Gupta V, Kosiorek HE, Mead A, Klisovic RB, Galvin JP, Berenzon D, Yacoub A, Viswabandya A, Mesa RA, Goldberg J, Price L, Salama ME, Weinberg RS, Rampal R, Farnoud N, Dueck AC, Mascarenhas JO, Hoffman R. Ruxolitinib Therapy Followed by Reduced-Intensity Conditioning for Hematopoietic Cell Transplantation for Myelofibrosis: Myeloproliferative Disorders Research Consortium 114 Study. Biol Blood Marrow Transplant. 2019 Feb;25(2):256-264. doi: 10.1016/j.bbmt.2018.09.001. Epub 2018 Sep 8.

    PubMed 30205231

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ruxolitinib Pre- Hematopoietic cell transplantation (HCT) in people with Primary Myelofibrosis and Post Polycythemia Vera Myelofibrosis, run by John Mascarenhas at 8 sites in 3 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 19 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 20 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States, Canada, United Kingdom. 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 20 Mar 2019). 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?

Percent of Participants With 100-day Survival Without Graft Failure (time frame: Day 100-post allogeneic stem cell transplantation). 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 NCT01790295, 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 20 Mar 2019.

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