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Use Of A Response-Adapted Ruxolitinib-Containing Regimen For The Treatment Of Hemophagocytic Lymphohistiocytosis

Primary Purpose

Hemophagocytic Lymphohistiocytosis

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Ruxolitinib
Dexamethasone
Etoposide
Sponsored by
St. Jude Children's Research Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hemophagocytic Lymphohistiocytosis focused on measuring Hemophagocytic lymphohistiocytosis, Newly Diagnosed, Frontline therapy, Refractory, Relapsed, Response-adapted, Salvage therapy

Eligibility Criteria

6 Weeks - 22 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Frontline Arm:

  1. Patient is ≥6 weeks and ≤22 years of age.
  2. Patient weighs ≥3 kg.
  3. Patient is able to take medication PO and/or patient or parent is willing to have NG tube placed if patient is unable to take medications PO.
  4. Patient has active HLH if ≥5 of 8 HLH-2004 diagnostic criteria listed below OR patient has known fHLH (e.g., patient has pathogenic/likely pathogenic germline variant(s) in genes such as PRF1, UNC13D, STX11, STXBP2, LYST, RAB27A, XIAP, SH2D1A, NLCR4) and meets ≥4 of the HLH-2004 diagnostic criteria listed below:

    • Fever
    • Splenomegaly
    • Cytopenias affecting ≥2 of 3 cell lineages in the peripheral blood (hemoglobin <9 g/dL, platelets <100 × 10^9/L, neutrophils <1000 × 10^6/L)
    • Hypertriglyceridemia (fasting triglycerides ≥265 mg/dL) or hypofibrinogenemia (fibrinogen ≤150 g/dL)
    • Presence of hemophagocytosis in BM or other tissues
    • Low or absent NK-cell activity OR decreased CD107a mobilization
    • Ferritin ≥500 ng/mL
    • Soluble IL-2 receptor (CD25) ≥2400 U/mL
  5. Patient has not received prior HLH therapy, except steroids (any dose is allowed, but patient must not have been treated for more than 2 consecutive weeks) OR anakinra (any dose or length of therapy is allowed).
  6. Patient, parent, or legal authorized representative (LAR) must provide informed consent.

Inclusion Criteria: Salvage Arm:

  1. Patient is ≥6 weeks and ≤22 years of age.
  2. Patient weighs ≥3 kg.
  3. Patient or parent is willing to have the NG tube placed if patient is unable to take medications PO.
  4. Patient has past history of HLH, defined as meeting ≥5 of 8 HLH- 2004 diagnostic criteria for those with no known HLH-associated mutations, OR ≥4 of 8 HLH-2004 diagnostic criteria for those with known familial disease.
  5. Patient must have active HLH at the time of eligibility assessment, defined as 3 or more of the following Relapsed/Refractory HLH Criteria:

    • Fever
    • Splenomegaly (recurrent or worsening)
    • Neutrophils <1000 × 10^6/L × 2 assessments over at least 3 days OR platelets <100 × 10^9/L × 2 assessments over at least 3 days, OR need for platelet transfusions
    • Hypofibrinogenemia (fibrinogen <150 g/dL)
    • Soluble IL-2 receptor level ≥ 2400 U/L
    • Worsening CNS symptoms OR new abnormal brain magnetic resonance imaging (MRI) findings deemed consistent with CNS HLH by the primary treating physician OR CSF cell count >5 (with or without hemophagocytosis) OR CSF protein higher than the institutional upper limit of normal OR CSF neopterin higher than the institutional upper limit of normal
    • Presence of hemophagocytosis in the BM or other tissues
    • Increasing ferritin × 2 assessments over at least 3 days (both levels must be >2000 ng/dL)
  6. Patient must be deemed by the primary treating physician to have not responded to prior therapy by either not having or maintaining a response
  7. Patient must have received prior HLH-directed therapy:

    • At least 2 weeks of steroids (equivalent to at least 5 mg/m^2/day dexamethasone or 1 mg/kg/day methylprednisolone) AND at least 2 doses of etoposide (with at least 7 days between the last etoposide dose and starting ruxolitinib); OR
    • At least 1 dose of ATG (with at least 7 days between the last ATG dose and starting ruxolitinib)
  8. Patient or parent/LAR must provide informed consent.

Exclusion Criteria: Frontline and Salvage Arms:

  1. Patient is <6 weeks or >22 years of age.
  2. Patient weighs <3 kg.
  3. Patient has isolated CNS disease.
  4. Life expectancy is <2 weeks.
  5. Patient is likely to require <4 weeks of therapy (i.e., HSCT is imminent).
  6. Patients with creatinine clearance (CrCl) <15 mL/min who are NOT receiving dialysis.
  7. Patient has evidence of severe organ dysfunction, defined as: Severe liver dysfunction (ALT >1000 U/L), OR Cardiorespiratory failure requiring any ionotropic support OR extracorporeal life support, OR high frequency oscillatory ventilation, other forms of respiratory support or ventilation are allowed if the patient is not on vasopressors)
  8. Patient with pre-existing rheumatologic disorder.
  9. Patient with known active malignancy.
  10. Patient with previous HSCT, except when HSCT was for treatment of HLH.
  11. Patient is pregnant or lactating.
  12. Patients who expect to conceive or father children within the projected duration of the study and/or who are unwilling to use highly effective methods of contraception throughout the duration of the study, starting with the screening visit through the end of the treatment visit.
  13. Patient has suspected or known fungal disease.
  14. Patient is unable to tolerate administration of drugs PO or NG.
  15. Patient is taking rifampin or St. John's Wort.
  16. Patient is taking another investigational agent or is enrolled on another treatment protocol.
  17. Patient, parent, or LAR are unable or unwilling to provide informed consent.

Additional Exclusion Criteria for the Frontline Arm:

  1. Patient has or is receiving treatment with a JAK inhibitor (including ruxolitinib), ATG, alemtuzumab, etoposide, tocilizumab, emapalumab or any other HLH-directed therapy other than steroids or anakinra (as defined in the Frontline Arm Inclusion Criteria, #5).

Additional Exclusion Criteria for the Salvage Arm:

  1. Patient has or is receiving treatment with a JAK inhibitor (including ruxolitinib), tocilizumab, alemtuzumab, OR emapalumab within the last 3 months.
  2. Patient has received therapy on the Frontline Arm of this trial.

Sites / Locations

  • Phoenix Children's HospitalRecruiting
  • Children's Hospital of Orange CountyRecruiting
  • University of California San FranciscoRecruiting
  • Children's National Medical CenterRecruiting
  • John Hopkins UniversityRecruiting
  • Dana-Farber Cancer InstituteRecruiting
  • Cohen Children's Medical CenterRecruiting
  • Levine Children's HospitalRecruiting
  • Children's Hospital of PhiladelphiaRecruiting
  • St. Jude Children's Research HospitalRecruiting
  • Children's Wisconsin/Medical College of WisconsinRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Frontline Arm

Salvage Arm

Arm Description

Safety Phase: Patients with newly diagnosed HLH will receive ruxolitinib PO or NGT, dexamethasone, PO or IV and etoposide IV. Expansion Phase: Patients with newly diagnosed HLH treatment will begin with ruxolitinib PO or NGT at the MTD dose. Dexamethasone will be administered PO or IV. Etoposide IV will be added based on disease response.

Patients with relapsed/refractory HLH will receive ruxolitinib PO or NGT and dexamethasone PO or IV. Etoposide IV will be added based on disease response.

Outcomes

Primary Outcome Measures

Complete Response (CR)/Complete Response with Incomplete Hematologic Recovery (CRi)
Will be reported as number and percentage of patients meeting CR/CRi criteria at the end of 8 weeks of therapy
Adverse events (AEs) associated with the ruxolitinib-containing regimen
Cumulative incidence will be estimated by the Kalbfleisch-Prentice method for severe toxicities that lead to morbidity and mortality.
Adverse events (AEs) associated with the ruxolitinib-containing regimen
Cumulative incidence will be estimated by the Kalbfleisch-Prentice method for severe toxicities that lead to morbidity and mortality.

Secondary Outcome Measures

Overall Response (CR/CRi plus Partial Response [PR]))
Will be reported as number and percentage/proportion of patients meeting response (CR/CRi plus PR) criteria at the end of 8 weeks of therapy
Survival to eight weeks
The proportion (probability) of patients surviving to the end of 8 weeks will be estimated by sample proportions along with the 95% exact binomial CIs in the Frontline and Salvage Arms, respectively.
Survival to allogeneic hematopoietic stem cell transplantation (HSCT) in patients for whom an allogeneic HSCT is planned
The proportion (probability) of surviving to HSCT will be estimated by sample proportions along with 95% exact binomial CIs in the Frontline and Salvage Arms, respectively.
Survival to one year after initiation of the treatment protocol
One-year Overall Survival (OS) rate will be estimated in all patients
Survival one year after HSCT
One-year post-HSCT Overall Survival (OS) rate will be estimated in patients who receive transplantation, in the Frontline and Salvage Arms, respectively.
Time to Response (CR/CRi or PR)
The mean time to CR/PR including CRi for week 8 response evaluation (will be estimated by the sample mean along with 95% CIs, in the Frontline and Salvage Arms, respectively. The median time will be estimated by the sample median along with the 95% finite- sample CI.

Full Information

First Posted
September 2, 2020
Last Updated
September 21, 2023
Sponsor
St. Jude Children's Research Hospital
Collaborators
Incyte Corporation, North American Consortium for Histiocytosis, Cures Within Reach
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1. Study Identification

Unique Protocol Identification Number
NCT04551131
Brief Title
Use Of A Response-Adapted Ruxolitinib-Containing Regimen For The Treatment Of Hemophagocytic Lymphohistiocytosis
Official Title
Use Of A Response-Adapted Ruxolitinib-Containing Regimen For The Treatment Of Hemophagocytic Lymphohistiocytosis
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 13, 2021 (Actual)
Primary Completion Date
August 2025 (Anticipated)
Study Completion Date
August 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
St. Jude Children's Research Hospital
Collaborators
Incyte Corporation, North American Consortium for Histiocytosis, Cures Within Reach

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study is a multi-site Phase Ib/II, 2-arm non-randomized clinical trial to determine the efficacy and tolerability of a response-adapted regimen combining ruxolitinib, dexamethasone, and etoposide as Frontline therapy for patients with newly diagnosed hemophagocytic lymphohistiocytosis (HLH) or as Salvage therapy for patients with relapsed/refractory HLH. Primary Objective To determine the efficacy and tolerability of a response-adapted ruxolitinib-containing regimen for patients with newly diagnosed HLH. Secondary Objectives To describe the efficacy and tolerability of a response-adapted ruxolitinib-containing regimen for patients with relapsed/refractory HLH. To describe the overall response and outcome for patients with newly diagnosed or relapsed/refractory HLH who are treated with this response-adapted ruxolitinib-containing regimen. Exploratory Objectives To estimate the pharmacokinetic (PK) parameters of ruxolitinib, assess covariates of ruxolitinib pharmacokinetics, and test whether the drug's effectiveness is correlated with systemic drug exposure. To query specific immunologic biomarkers and determine whether the levels of these biomarkers correlate with disease response and outcome.
Detailed Description
Frontline Arm: Safety Phase and Expansion Phase Safety Phase: The Frontline Arm will begin with a Safety Phase to identify a feasible and safe dose of ruxolitinib to be given in combination with the "gold standard" HLH-directed agents dexamethasone and etoposide. For this part of the trial, a minimum of 6 newly diagnosed HLH patients will be included. These patients will first receive ruxolitinib 25 mg/m^2/dose by mouth BID (twice a day), dexamethasone 5 mg/m^2/dose PO or IV BID, and etoposide 150 mg/m^2/dose IV weekly. Etoposide dosing is to be initiated within the first 24-48 hours. The first dose of dexamethasone and etoposide will be at least 8 hours after the first dose of ruxolitinib for PK testing purposes, but patients will not be excluded if dexamethasone has already been started before initiating ruxolitinib. The dose of ruxolitinib may be escalated or de-escalated as needed, based on observed toxicities and surrogates of disease response. Dexamethasone will be weaned every 2 weeks. In case of disease reactivation, patients will receive individualized re-intensification. Expansion Phase: When a dose of ruxolitinib deemed feasible and safe is identified, the Expansion Phase of the Frontline Arm will begin. Patients with newly diagnosed HLH in the Expansion Phase will receive ruxolitinib (at the maximally tolerated dose [MTD] established in the Safety Phase) and dexamethasone 5 mg/m^2/dose by mouth or IV BID. The first dose of dexamethasone will be given at least 8 hours after the first dose of ruxolitinib for PK testing purposes, but patients will not be excluded if dexamethasone has already been started before initiating of ruxolitinib. Disease response evaluations will be completed at 1, 2, 4, 6, and 8 weeks. Treatment will be individualized based on response. Patients whose HLH responds favorably after 1 week (SD 8) of therapy (e.g., favorable response (FR), Week 1) will remain on ruxolitinib and dexamethasone. As long as patients show a CR or partial response (PR) at Week 2 (SD15), ruxolitinib and dexamethasone are tolerated, and patients are clinically stable, they will remain on both agents for the remainder of the 8-week study period. Dexamethasone will be weaned every 2 weeks as tolerated. In case of disease reactivation, therapy will be re-intensified. Patients whose HLH responds unfavorably after 1 week (SD8) of therapy (e.g., unfavorable response, Week 1) will have etoposide added (150 mg/m^2/dose, IV weekly). If patient meets CR or PR at Week 2 (SD15), then combination treatment with ruxolitinib, dexamethasone, and etoposide will be continued until Week 4 disease evaluation (SD 29). If patients have a CR or PR at the Week 4 disease evaluation (SD 29) or later, further etoposide doses may be held at site PI discretion. Dexamethasone weaning may continue beyond the 8-week study period. Patients whose HLH does not respond favorably (e.g., exhibit non-response (NR), progressive disease (PD)) despite treatment with ruxolitinib, dexamethasone, and etoposide will be taken off treatment and salvage therapy will be considered and decided by the treating physician. Salvage Arm: Patients with relapsed/refractory HLH will be treated on the Salvage Arm. They will not be included in the Safety Phase; instead, they will be treated using the response-adapted approach. Patients may be enrolled on the Salvage Arm as the Safety Phase is ongoing. Patients will receive ruxolitinib 25 mg/m^2/dose by mouth BID and dexamethasone 5 mg/m^2/dose by mouth or IV BID. The first dose of dexamethasone will be given at least 8 hours after the first dose of ruxolitinib for PK testing purposes, but patients will not be excluded if dexamethasone has already been started before starting ruxolitinib. Disease response evaluations will be completed at 1, 2, 4, 6, and 8 weeks. Treatment will be individualized based on response as described for the Expansion Phase of the Frontline Arm. When the MTD of ruxolitinib has been determined on the Safety Phase of the Frontline Arm, it will be the dose used for any additional patients enrolled on the Salvage Arm. Any patients already on the Salvage Arm who show no adverse effects or toxicity at an assigned dose of 25 mg/m^2 BID will be continued on this dose for the 8 week study period. HLH Reactivation: For patients who initially respond favorably but then worsen (e.g., "reactivate") during the later phases of induction when dexamethasone is weaned, dexamethasone will be increased back to 5 mg/m^2/dose PO/IV BID (10 mg/m^2/day). If the patient is on a reduced dose of ruxolitinib due to prior toxicity(ies), the ruxolitinib dose may be increased to patient's starting dose, provided the prior toxicity(ies) has resolved for at least 1 week. Patients whose HLH responds favorably will continue to receive ruxolitinib and dexamethasone or ruxolitinib, dexamethasone and etoposide. Patients receiving ruxolitinib, dexamethasone and etoposide whose HLH responds unfavorably will be taken off treatment and be considered for an alternative salvage therapy. For patients receiving ruxolitinib and dexamethasone whose HLH responds unfavorably, etoposide may be added. If the response is favorable, the patient will continue on all 3 medications. If the response is unfavorable after adding etoposide, the patient will be taken off treatment and will be considered for an alternative salvage therapy. All patients with CNS disease will receive intrathecal (IT) MTX and hydrocortisone (HC), per age-based dosing, once per week for up to 4 weeks. Patients will be followed for one year after starting protocol therapy or 1 year after HSCT (for those undergoing HSCT).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophagocytic Lymphohistiocytosis
Keywords
Hemophagocytic lymphohistiocytosis, Newly Diagnosed, Frontline therapy, Refractory, Relapsed, Response-adapted, Salvage therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
62 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Frontline Arm
Arm Type
Experimental
Arm Description
Safety Phase: Patients with newly diagnosed HLH will receive ruxolitinib PO or NGT, dexamethasone, PO or IV and etoposide IV. Expansion Phase: Patients with newly diagnosed HLH treatment will begin with ruxolitinib PO or NGT at the MTD dose. Dexamethasone will be administered PO or IV. Etoposide IV will be added based on disease response.
Arm Title
Salvage Arm
Arm Type
Experimental
Arm Description
Patients with relapsed/refractory HLH will receive ruxolitinib PO or NGT and dexamethasone PO or IV. Etoposide IV will be added based on disease response.
Intervention Type
Drug
Intervention Name(s)
Ruxolitinib
Other Intervention Name(s)
Jakafi®
Intervention Description
Given orally (PO) or per nasogastric tube (NGT) twice a day for 8 weeks
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Other Intervention Name(s)
Decadron®, Hexadrol®, Dexone®, Dexameth®
Intervention Description
Given intravenously (IV) or orally (PO) twice a day for 8 weeks
Intervention Type
Drug
Intervention Name(s)
Etoposide
Other Intervention Name(s)
Etoposide Phosphate, VePesid®, Etopophos®, VP-16
Intervention Description
Given intravenously (IV) once a week for 8 weeks
Primary Outcome Measure Information:
Title
Complete Response (CR)/Complete Response with Incomplete Hematologic Recovery (CRi)
Description
Will be reported as number and percentage of patients meeting CR/CRi criteria at the end of 8 weeks of therapy
Time Frame
8 weeks
Title
Adverse events (AEs) associated with the ruxolitinib-containing regimen
Description
Cumulative incidence will be estimated by the Kalbfleisch-Prentice method for severe toxicities that lead to morbidity and mortality.
Time Frame
up to 8 weeks
Title
Adverse events (AEs) associated with the ruxolitinib-containing regimen
Description
Cumulative incidence will be estimated by the Kalbfleisch-Prentice method for severe toxicities that lead to morbidity and mortality.
Time Frame
up to 1 year after diagnosis
Secondary Outcome Measure Information:
Title
Overall Response (CR/CRi plus Partial Response [PR]))
Description
Will be reported as number and percentage/proportion of patients meeting response (CR/CRi plus PR) criteria at the end of 8 weeks of therapy
Time Frame
8 weeks
Title
Survival to eight weeks
Description
The proportion (probability) of patients surviving to the end of 8 weeks will be estimated by sample proportions along with the 95% exact binomial CIs in the Frontline and Salvage Arms, respectively.
Time Frame
8 weeks
Title
Survival to allogeneic hematopoietic stem cell transplantation (HSCT) in patients for whom an allogeneic HSCT is planned
Description
The proportion (probability) of surviving to HSCT will be estimated by sample proportions along with 95% exact binomial CIs in the Frontline and Salvage Arms, respectively.
Time Frame
up to 1 year
Title
Survival to one year after initiation of the treatment protocol
Description
One-year Overall Survival (OS) rate will be estimated in all patients
Time Frame
1 year after initiation of treatment
Title
Survival one year after HSCT
Description
One-year post-HSCT Overall Survival (OS) rate will be estimated in patients who receive transplantation, in the Frontline and Salvage Arms, respectively.
Time Frame
1 year post HSCT
Title
Time to Response (CR/CRi or PR)
Description
The mean time to CR/PR including CRi for week 8 response evaluation (will be estimated by the sample mean along with 95% CIs, in the Frontline and Salvage Arms, respectively. The median time will be estimated by the sample median along with the 95% finite- sample CI.
Time Frame
At weeks 2, 4, 6, and 8

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Weeks
Maximum Age & Unit of Time
22 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Frontline Arm: Patient is ≥6 weeks and ≤22 years of age. Patient weighs ≥3 kg. Patient is able to take medication PO and/or patient or parent is willing to have NG tube placed if patient is unable to take medications PO. Patient has active HLH if: Patient has ≥5 of 8 Diagnostic HLH criteria listed below, OR Patient has known fHLH (e.g., patient has pathogenic/likely pathogenic germline variant(s) in genes such as PRF1, UNC13D, STX11, STXBP2, LYST, RAB27A, XIAP, SH2D1A, NLCR4) and meets ≥4 of the diagnostic HLH criteria listed below, OR Patient has high likelihood of fHLH based on absent perforin, SAP, XIAP expression and meets ≥4 of the Diagnostic HLH Criteria listed below: Fever Splenomegaly (If present at any point prior to starting study drug) Cytopenias affecting ≥2 of 3 cell lineages in the peripheral blood (hemoglobin <9 g/dL, platelets <100 × 10^9/L, neutrophils <1000 × 10^6/L) Hypertriglyceridemia (fasting triglycerides ≥265 mg/dL) or hypofibrinogenemia (fibrinogen ≤150 g/dL) Presence of hemophagocytosis in BM or other tissues Low or absent NK-cell activity (if present at any point prior to starting study drug) OR decreased CD107a mobilization (if present at any point prior to starting study drug) Ferritin ≥500 ng/mL Soluble IL-2 receptor (CD25) ≥2400 U/mL Patient has not received prior HLH therapy, except steroids (any dose or length of therapy is allowed) OR anakinra (any dose or length of therapy is allowed). Patient, parent, or legal authorized representative (LAR) must provide informed consent. Inclusion Criteria: Salvage Arm: Patient is ≥6 weeks and ≤22 years of age. Patient weighs ≥3 kg. Patient or parent is willing to have the NG tube placed if patient is unable to take medications PO. Patient has past history of HLH, defined as meeting ≥5 of 8 HLH- 2004 diagnostic criteria for those with no known HLH-associated mutations, OR ≥4 of 8 HLH-2004 diagnostic criteria for those with known familial disease. Patient must have active HLH at the time of eligibility assessment, defined as 3 or more of the following Relapsed/Refractory HLH Criteria: Fever Splenomegaly (recurrent or worsening) Neutrophils <1000 × 10^6/L × 2 assessments over at least 3 days OR platelets <100 × 10^9/L × 2 assessments over at least 3 days, OR need for platelet transfusions Hypofibrinogenemia (fibrinogen <150 g/dL) Soluble IL-2 receptor level ≥ 2400 U/L Worsening CNS symptoms OR new abnormal brain magnetic resonance imaging (MRI) findings deemed consistent with CNS HLH by the primary treating physician OR CSF cell count >5 (with or without hemophagocytosis) OR CSF protein higher than the institutional upper limit of normal OR CSF neopterin higher than the institutional upper limit of normal Presence of hemophagocytosis in the BM or other tissues Increasing ferritin × 2 assessments over at least 3 days (both levels must be >2000 ng/dL) Patient must be deemed by the primary treating physician to have not responded to prior therapy by either not having or maintaining a response Patient must have received prior HLH-directed therapy: At least 2 weeks of steroids (equivalent to at least 5 mg/m^2/day dexamethasone or 1 mg/kg/day methylprednisolone) AND at least 2 doses of etoposide (with at least 7 days between the last etoposide dose and starting ruxolitinib); OR At least 1 dose of ATG (with at least 7 days between the last ATG dose and starting ruxolitinib) Patient or parent/LAR must provide informed consent. Exclusion Criteria: Frontline and Salvage Arms: Patient is <6 weeks or >22 years of age. Patient weighs <3 kg. Patient has isolated CNS disease. Life expectancy is <2 weeks. Patient is likely to require <4 weeks of therapy (i.e., HSCT is imminent). Patients with creatinine clearance (CrCl) <15 mL/min who are NOT receiving dialysis. Patient has evidence of severe organ dysfunction, defined as: Severe liver dysfunction (ALT >1000 U/L), OR Cardiorespiratory failure requiring any ionotropic support OR extracorporeal life support, OR high frequency oscillatory ventilation, other forms of respiratory support or ventilation are allowed if the patient is not on vasopressors) Patient with pre-existing rheumatologic disorder. Patient with known active malignancy. Patient with previous HSCT, except when HSCT was for treatment of HLH. Patient is pregnant or lactating. Patients who expect to conceive or father children within the projected duration of the study and/or who are unwilling to use highly effective methods of contraception throughout the duration of the study, starting with the screening visit through the end of the treatment visit. Patient has suspected or known fungal disease. Patient is unable to tolerate administration of drugs PO or NG. Patient is taking rifampin or St. John's Wort. Patient is taking another investigational agent or is enrolled on another treatment protocol. Patient, parent, or LAR are unable or unwilling to provide informed consent. Additional Exclusion Criteria for the Frontline Arm: Patient has or is receiving treatment with a JAK inhibitor (including ruxolitinib), ATG, alemtuzumab, etoposide, tocilizumab, emapalumab or any other HLH-directed therapy other than steroids or anakinra (as defined in the Frontline Arm Inclusion Criteria, #5). Additional Exclusion Criteria for the Salvage Arm: Patient has or is receiving treatment with a JAK inhibitor (including ruxolitinib) or alemtuzumab within the last 3 months. Patient has received therapy on the Frontline Arm of this trial.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Melissa Hines, MD
Phone
866-278-5833
Email
referralinfo@stjude.org
First Name & Middle Initial & Last Name or Official Title & Degree
Kim E. Nichols, MD
Phone
866-278-5833
Email
referralinfo@stjude.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Melissa Hines, MD
Organizational Affiliation
St. Jude Children's Research Hospital
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Kim E. Nichols, MD
Organizational Affiliation
St. Jude Children's Research Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Phoenix Children's Hospital
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85016
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michael Henry, MD
Phone
602-933-5011
Email
mhenry@phoenixchildrens.com
First Name & Middle Initial & Last Name & Degree
Michael Henry, MD
Facility Name
Children's Hospital of Orange County
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lilibeth Torno, MD
Phone
714-509-4348
Email
ltorno@choc.org
First Name & Middle Initial & Last Name & Degree
Lilibeth Torno, MD
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michelle Hermiston, MD
Phone
415-476-2413
Email
michelle.hermiston@ucsf.edu
First Name & Middle Initial & Last Name & Degree
Michelle Hermiston, MD
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Birte Wistinghausen, MD
Phone
202-476-5000
Email
bwistingha@childrensnational.org
First Name & Middle Initial & Last Name & Degree
Birte Wistinghausen, MD
Facility Name
John Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elias Zambidis, MD, PhD
Phone
410-502-4997
Email
ezambid1@jhmi.edu
First Name & Middle Initial & Last Name & Degree
Elias Zambidis, MD, PhD
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Barbara Degar, MD
Phone
617-632-5186
Email
Barbara_Degar@dfci.harvard.edu
First Name & Middle Initial & Last Name & Degree
Barbara Degar, MD
Facility Name
Cohen Children's Medical Center
City
New Hyde Park
State/Province
New York
ZIP/Postal Code
11040
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anshul Vagrecha, MD
Phone
718-470-3460
Email
avagrecha@northwell.edu
First Name & Middle Initial & Last Name & Degree
Anshul Vagrecha, MD
Facility Name
Levine Children's Hospital
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28203
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Gass, MD
Phone
980-442-2310
Email
David.Gass@atriumhealth.org
First Name & Middle Initial & Last Name & Degree
David Gass, MD
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Teachey, MD
Phone
267-426-5802
Email
teacheyd@chop.edu
First Name & Middle Initial & Last Name & Degree
David Teachey, MD
Facility Name
St. Jude Children's Research Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Melissa Hines, MD
Phone
866-278-5833
Email
referralinfo@stjude.org
First Name & Middle Initial & Last Name & Degree
Melissa Hines, MD
First Name & Middle Initial & Last Name & Degree
Kim E. Nichols, MD
Facility Name
Children's Wisconsin/Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Julie-An Talano, MD
Phone
414-955-4185
Email
jtalano@mcw.edu
First Name & Middle Initial & Last Name & Degree
Julie-An Talano, MD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.
IPD Sharing Time Frame
Data will be made available at the time of article publication.
IPD Sharing Access Criteria
Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.
Links:
URL
http://www.stjude.org
Description
St. Jude Children's Research Hospital
URL
http://www.stjude.org/protocols
Description
ClinicalTrials Open at St. Jude

Learn more about this trial

Use Of A Response-Adapted Ruxolitinib-Containing Regimen For The Treatment Of Hemophagocytic Lymphohistiocytosis

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