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Primary MyelofibrosisPhase 1NCT02917096

Ruxolitinib Phosphate and Chemotherapy Given Before and After Reduced Intensity Donor Stem Cell Transplant in Treating Patients With Myelofibrosis

A Phase 1 study testing Allogeneic Hematopoietic Stem Cell Transplantation, Fludarabine and Fludarabine Phosphate in people with Primary Myelofibrosis and Secondary Myelofibrosis, run by City of Hope Medical Center at 1 site 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 pilot clinical trial studies the side effects and best dose of ruxolitinib phosphate when given together with chemotherapy before and after a donor stem cell transplant in treating patients with myelofibrosis. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Allogeneic Hematopoietic Stem Cell Transplantation, Fludarabine and Fludarabine Phosphate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteUnited States
Study dates
13 Nov 2016to 31 Aug 2023
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 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Primary or secondary myelofibrosis intermediate or high risk by Dynamic International Prognostic Scoring System (DIPSS) in chronic or accelerated phase
  • Performance status of >= 70% on the Karnofsky scale
  • The effects of chemotherapy, ruxolitinib on the developing fetus are unknown; for this reasonWomen of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for 1 year following transplant as per City of Hope standard operating procedure (SOP) for allogeneic transplantation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
  • Bone marrow and peripheral blood studies must be available for confirmation of diagnosis; cytogenetics, flow cytometry, and molecular studies (such as JAK-2, MPL and CALR mutational status) will be obtained as per standard practice
  • Bone marrow aspirates/biopsies should be performed within 30 +/- 3 days from registration to confirm disease remission status
  • All candidates for this study must have a human leukocyte antigen (HLA) (A, B, C, DR) identical siblings who is willing to donate bone marrow for primed blood stem cells or an 8/8 allele-matched unrelated donor
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  • All ABO blood group combinations of the donor/recipient are acceptable since even major ABO compatibilities can be dealt with by various techniques (red cell exchange or plasma exchange)
  • A cardiac evaluation with an electrocardiogram showing no ischemic changes or abnormal rhythm and an ejection fraction of 50% established by multi-gated acquisition scan (MUGA) or echocardiogram
  • Patients must have creatinine of less than or equal to 1.5 mg/dL or creatinine clearance > 60 ml/min
  • A bilirubin of up to 2.0 mg/dL, excluding patients with Gilbert's disease
  • Patients should also have a serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) less than 5 times the upper limit of normal
  • Pulmonary function test including diffusion capacity of the lung for carbon monoxide (DLCO) will be performed; forced expiratory volume in 1 second (FEV1) and DLCO should be greater than 50% of predicted normal value
  • All subjects must have the ability to understand and the willingness to sign a written informed consent that has been approved by the City of Hope Institutional Review Board (COH IRB); the patient, a family member and transplant staff physician (physician, nurse, social worker) will meet at least once prior to the subject signing consent; during this meeting all pertinent information with respect to risks and benefits to donor and recipient will be presented; alternative treatment modalities will be discussed; the risks are explained in detail in the enclosed consent form
  • Prior therapy with hydroxyurea, interferon, anagrelide, ruxolitinib, hypomethylating agents, revlimid, thalidomide, steroids, other JAK inhibitors is allowed; for acute myeloid leukemia (AML) patients who are back in chronic phase myeloproliferative neoplasm (MPN), prior induction therapy is allowed

Who cannot join

  • Patients should not have any uncontrolled illnesses including ongoing or active infection
  • Patients may not be receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to ruxolitinib
  • Pregnant women are excluded from this study because ruxolitinib is an agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ruxolitinib, breastfeeding should be discontinued if the mother is treated with ruxolitinib
  • Patients with active 2nd malignancies other than myelofibrosis, AML, excised skin cancer, early stage cervical and prostate cancer
  • Previous allogeneic hematopoietic stem cell transplantation
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  • Any psychiatric, social or compliance issues that, in the treating physician opinion, will interfere with completion of the transplant treatment and follow up
  • Patients who have been treated with chemotherapy or radiation within two weeks of planned study enrollment; this does not include hydroxyurea, which may be continued until start of conditioning therapy; ruxolitinib may be continued at principal investigator's discretion during conditioning
  • Non-compliance; defined as any subject, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study

Trial locations and contacts

1 site in 1 country.

United States1 site

  • City of Hope Medical Center

    Duarte, California, 91010

Other trials in United States

About this study

Official title: Pilot Open-Label Study of Safety and Efficacy of Ruxolitinib Given Peri-Transplant During Reduced Intensity Allogeneic Hematopoietic Cell Transplantation (HCT) in Patients With Myelofibrosis

This pilot clinical trial studies the side effects and best dose of ruxolitinib phosphate when given together with chemotherapy before and after a donor stem cell transplant in treating patients with myelofibrosis. Ruxolitinib phosphate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fludarabine phosphate and melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ruxolitinib phosphate together with chemotherapy before and after a donor stem cell transplant may help stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. The donated stem cells may also replace the patient?s immune cells and help destroy any remaining cancer cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Among the dose levels tested, to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of ruxolitinib phosphate (ruxolitinib), when given as part of reduced intensity allogeneic hematopoietic cell transplant (HCT), in patients with myelofibrosis.

II. To determine if the addition of ruxolitinib is safe by evaluation of toxicities including: type, frequency, severity, attribution, time course and duration.

SECONDARY OBJECTIVES:

  1. To characterize and evaluate hematologic recovery, donor cell engraftment and immune reconstitution by cell count and flow cytometry of lymphocyte subsets.

II. To estimate the cumulative incidence of acute graft-versus-host disease (aGVHD) and non-relapse mortality (NRM) at 100-days post transplant.

III. To estimate the cumulative incidence of chronic GVHD at 1- and 2-years post transplant.

IV. To estimate the probabilities of overall and progression-free survival (OS/PFS) at 1- and 2-years post transplant.

  1. To characterize changes in aGVHD biomarkers (Reg-3 alpha, soluble tumor necrosis factor receptor I [sTNF RI], IL2R alpha), janus associated kinases (JAK)-regulated pro-inflammatory cytokines (i.e. IL-6, TNF alpha, CRP, beta 2microglobulin) and STAT3 phosphorylation (downstream of JAK signaling) over time and by aGVHD status/grade.

OUTLINE: This is a dose-escalation study of ruxolitinib phosphate.

PREPARATIVE REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days -9 to -5, melphalan IV over 20 minutes on day -4, and ruxolitinib phosphate orally (PO) twice daily (BID) on days -3 to 30 with a taper for 2-3 weeks in the absence of disease progression or unacceptable toxicity.

GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously beginning on day -3 and convert to PO daily when the patient is able to tolerate and absorb oral medications. Patients also receive sirolimus PO daily beginning on day -3. Treatment continues in the absence of GVHD.

STEM CELL TRANSPLANT: Patients undergo allogeneic HCT on day 0.

After completion of study treatment, patients are followed up for 2 years.

Medical subject headings
Primary Myelofibrosis

What participants receive

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

  • Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery

    Also called Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT

    Undergo allogeneic HCT

  • FludarabineDrug

    Also called Fluradosa

    Given IV

  • Fludarabine PhosphateDrug

    Also called 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • MelphalanDrug

    Also called Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard

    Given IV

  • Pharmacological StudyOther

    Correlative studies

  • RuxolitinibDrug

    Also called INCB-18424, INCB18424, Oral JAK Inhibitor INCB18424

    Given PO

  • Ruxolitinib PhosphateDrug

    Also called INCB-18424 Phosphate, Jakafi

    Given PO

  • SirolimusDrug

    Also called AY 22989, RAPA, Rapamune, Rapamycin

    Given PO

  • TacrolimusDrug

    Also called FK 506, Fujimycin, Hecoria, Prograf

    Given IV and PO

Study groups in NCT02917096
Study groupRoleWhat they receive
Treatment (ruxolitinib phosphate, chemotherapy,allogeneic HCT)ExperimentalPREPARATIVE REGIMEN: Patients receive fludarabine phosphate IV on days -9 to -5, melphalan IV over 20 minutes on day -4, and ruxolitinib phosphate PO BID on days -3 to 30 with a taper for 2-3 weeks in the absence of disease progression or unacceptable toxicity. Patients being treated with ruxolitinib phosphate prior to allogeneic HCT as standard therapy may continue receiving ruxolitinib phosphate. GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously beginning on day -3 and convert to PO daily when the patient is able to tolerate and absorb oral medications. Patients also receive sirolimus PO daily beginning on day -3. Treatment continues in the absence of GVHD. STEM CELL TRANSPLANT: Patients undergo allogeneic HCT on day 0.
Receives: Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Fludarabine; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Drug: Melphalan; Other: Pharmacological Study; Drug: Ruxolitinib; Drug: Ruxolitinib Phosphate; Drug: Sirolimus; Drug: Tacrolimus

What is being measured

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

  1. Maximum tolerated dose of ruxolitinib phosphate, defined as less than or equal to 1 of 6 dose limiting toxicities, graded according to the Bearman criteria and the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03

    Will be summarized in terms of type (organ affected, or laboratory determination) severity, time of onset, duration, probable associates with the study treatment and reversibility or outcome.

    Measured: Up to 45 days post stem cell infusion

Secondary outcomes (8)

  1. Engraftment (recovery of granulopoiesis and megakaryopoiesis)

    Defined as absolute neutrophil count >= 0.5 x 10^3/ul sustained for 3 consecutive lab values on different days with no subsequent decline, and platelets >= 20 K/ul independent of platelet transfusion support.

    Measured: Up to 100 days post stem cell infusion

  2. Cumulative incidence of acute graft-versus-host disease (aGVHD), graded and staged according to the Consensus Grading

    Will be calculated using the Gray method with prior death or relapse considered competing events.

    Measured: Up to 100 days post stem cell infusion

  3. Cumulative incidence of chronic GVHD, graded and staged according to the Consensus Grading

    Will be calculated using the Gray method with prior death or relapse considered competing events.

    Measured: Up to 100 days post stem cell infusion

  4. Incidence of infections

    Will be reported by site of disease, date of onset, severity and resolution, if any.

    Measured: Up to 100 days post stem cell infusion

  5. Overall survival

    Will be calculated using the Kaplan-Meier method.

    Measured: From the day of stem cell infusion until death, or last follow-up, whichever occurs first, assessed for up to 2 years

  6. Progression-free survival

    Will be calculated using the Kaplan-Meier method.

    Measured: From the day of stem cell infusion to the date of death, disease relapse/progression, or last follow-up, whichever occurs first, assessed for up to 2 years

  7. Cumulative incidence of relapse/progression

    Will be calculated as a competing risk using the Gray method.

    Measured: Up to 2 years

  8. Non-relapse mortality, defined as death occurring in a patient from causes other than relapse or progression

    Will be calculated as a competing risk using the Gray method.

    Measured: 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.

  1. First posted28 Sep 2016 (estimated)
  2. Study start13 Nov 2016
  3. Primary completion16 Apr 2020
  4. Study completion31 Aug 2023

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
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02917096
Sponsor's protocol ID
16337
Other IDs
NCI-2016-01400, 16337
Status last verified
Dec 2023
First submitted
26 Sep 2016
Last updated
12 Dec 2023
Results posted
No
Data monitoring committee
Yes

Publications

  • Ali H, Tsai NC, Synold T, Mokhtari S, Tsia W, Palmer J, Stiller T, Al Malki M, Aldoss I, Salhotra A, Rahmanuddin S, Pullarkat V, Cai JL, Stein A, Forman SJ, Marcucci G, Mei M, Snyder DS, Nakamura R. Peritransplantation ruxolitinib administration is safe and effective in patients with myelofibrosis: a pilot open-label study. Blood Adv. 2022 Mar 8;6(5):1444-1453. doi: 10.1182/bloodadvances.2021005035.

    PubMed 34581764

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Allogeneic Hematopoietic Stem Cell Transplantation, Fludarabine and Fludarabine Phosphate in people with Primary Myelofibrosis and Secondary Myelofibrosis, run by City of Hope Medical Center at 1 site 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 9 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 12 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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?

Maximum tolerated dose of ruxolitinib phosphate, defined as less than or equal to 1 of 6 dose limiting toxicities, graded according to the Bearman criteria and the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 (time frame: Up to 45 days post stem cell infusion). 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 NCT02917096, 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 12 Dec 2023.

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