Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Polycythemia Vera

Polycythemia

Hematologic Diseases

Bone Marrow Neoplasms

Hematologic Neoplasms

Bone Marrow Diseases

Myeloproliferative Disorders

Chronic Myeloproliferative Disorders

Patients may self-administer daily ruxolitinib tablets qd or bid orally, without regard to food, in accordance with specified dosing schedule provided by the investigator.

Ruxolitinib

Novartis Pharmaceuticals

The purpose of this Cohort Treatment Plan is to allow access to ruxolitinib for eligible patients diagnosed with Polycythemia Vera. The patient's Treating Physician should follow the suggested treatment guidelines and comply with all local health authority regulations.

The requesting Treating Physician must submit a request for access to drug (often referred to as Compassionate Use) to Novartis which will review and approve by the medical team experienced with the drug and indication.

MAP to Provide Access to Ruxolitinib, for Patients With Polycythemia Vera

Treatment Plan for Managed Access Program (MAP) to Provide Access to Ruxolitinib, for Patients With Polycythemia Vera (PV)

Antineoplastic Agents

Antisickling Agents

All Drugs and Chemicals

Hydroxyurea

All patients will receive ruxolitinib at a starting dose of 10 mg twice daily which could be titrated to most appropriate dose. Dose was not to exceed 25 mg bid nor be less than 5 mg once a day

supplied as 5 mg, 10 mg and 20 mg tablets to be taken orally

The purpose of this open-label, single arm, multi-center Expanded Treatment Protocol (ETP) was to provide early access to ruxolitinib and evaluate safety information in patients with polycythemia vera (PV) who were hydroxyurea (HU) resistant or intolerant and who had no other standard treatment option, nor did they qualify for another clinical study for PV

Expanded Treatment Protocol (ETP) of Ruxolitinib in Patients With Polycythemia Vera Who Were Hydroxyurea Resistant or Intolerant and for Whom no Treatment Alternatives Was Available.

An Open-label, Multi-center, Expanded Treatment Protocol (ETP) of Ruxolitinib in Patients With Polycythemia Vera Who Are Hydroxyurea Resistant or Intolerant and for Whom no Treatment Alternatives Are Available.

Change in hematocrit levels from Baseline to each visit were measured

Change in spleen length from Baseline to each visit

The MPN-SAF (Appendix 6) was a disease specific questionnaire comprised of 10 items that measures fatigue related to MPN disease and the severity of nine of the most prevalent associated symptoms including: early satiety, abdominal discomfort, inactivity, concentration, night sweats, itching, bone pain, fever and weight loss. There were three recall periods used in this questionnaire, which were 24 hours for fatigue, the past week for symptoms of early satiety, abdominal discomfort, inactivity, concentration, night sweats, itching, bone pain and fever, and the past 6 months for weight loss, Each item was scored on a scale ranging from 0 (no fatigue/absent) to 10 (As bad as you can imagine/worst imaginable). The MPN-SAF TSS was computed as the average of the observed items multiplied by 10 to achieve a 0-to-100 scale.

The MPN-SAF TSS thus had a possible score range of 0 to 100.

All Patients

<= 60

Age, Customized

Sex: Female, Male

Caucasian

Asian

Other

Race/Ethnicity, Customized

Resistant to hydroxyurea

Intolerant to hydroxyurea

Definition of resistant or intolerant was based on physician's evaluation

Number of participants resistant or intolerant to hydroxyurea (HU)

1 phlebotomy

2 phlebotomies

>=3 phlebotomies

Missing

Number of participants' frequency of phlebotomy in 52 weeks prior to screening

Prior Hydroxyurea use

Prior other anti-neoplastic medications use

Other prior anti-neoplastic medications included busulfan, interferon, peginterferon, pipobroman, anagrelide, momelotinib, tioguanine, mercapturine and sodium phosphate

Number of participants' use of prior antineoplastic therapy

Study Director

Adverse events

Serious adverse events

Number of Participants With Adverse Events - All Grades

Week 4

Week 8

Week 12

Week 16

Week 20

Week 24

Week 36

Week 48

Week 60

Week 72

Week 84

Week 96

Baseline

Post-baseline

Change

Number of participants qualifying for evaluation of change from baseline varied across visits

Change From Baseline in Hematocrit Levels at All Visits

End of treatment

Change From Baseline in Spleen Length

Change From Baseline in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS)

Overall Study

Immune System Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Phase I - Starting dose of Ruxolitinib 50 mg by mouth twice a day for 28 day cycle.

Phase I dose of Ruxolitinib 100 mg by mouth twice a day for 28 day cycle.

Phase I dose of Ruxolitinib 200 mg by mouth twice a day for 28 day cycle.

Phase I - Starting dose of 50 mg by mouth twice a day for 28 day cycle.

Phase II - MTD reached in Phase I.

Srdan Verstovsek, MD

The goal of this clinical research study is to find the highest tolerable dose of ruxolitinib that can be given to patients with acute leukemia and to learn if the study drug can help control the disease. The safety of the drug will also be studied.

The Study Drug:

Ruxolitinib is designed to block a gene mutation that may be important in cancer cell growth and survival. By blocking the gene mutation, this may cause the cancer cells to die.

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you join this study. Up to 30 participants will be enrolled in the Phase I portion of the study, and up to 136 participants will be enrolled in Phase II.

If you are enrolled in the Phase I portion, the dose of ruxolitinib you receive will depend on when you joined this study. The first group of participants will receive the lowest dose level of ruxolitinib. Each new group will receive a higher dose of ruxolitinib than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of ruxolitinib is found.

If you are enrolled in the Phase II portion, you will receive ruxolitinib at the highest dose that was tolerated in the Phase I portion or at a lower dose.

Study Drug Administration:

You will take ruxolitinib tablet(s) by mouth 2 times a day on Days 1-28 of each 28-day study cycle.

You will be asked to keep a diary to record the doses taken. You will be asked to bring your diary and any unused drug to your next visit.

Study Visits:

On Days 1, 7, 14, and 21 of Cycle 1:

* You will have a physical exam.
* Blood (about 2 teaspoons) will be drawn for routine tests.
* You will be asked about any treatments you may have had, any other drugs you may be taking, and any side effects you may be having.
* On Day 14 only, you will have a bone marrow aspiration performed to check the status of the disease.

On Day 1 of Cycle 2:

* You will have a physical exam.
* You will be asked about any treatments you may have had, any other drugs you may be taking, and any side effects you may be having.
* Blood (about 2 teaspoons) will be drawn for routine tests.
* You will have a bone marrow aspiration performed to check the status of the disease.

During Cycles 2 and beyond, blood (about 2 teaspoons) will be drawn for routine tests at least every 1-2 weeks. This blood may be drawn at a clinic close to your home.

On Day 1 of Cycles 3, 6, 9, and beyond:

* You will have a physical exam.
* You will be asked about any treatments you may have had, any other drugs you may be taking, and any side effects you may be having.
* Blood (about 2 teaspoons) will be drawn for routine tests.
* You will have a bone marrow aspiration performed to check the status of the disease. On Day 1 of Cycle 3, this will only be done if your doctor thinks it is needed.

Length of Study:

You may continue taking the study drug for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drug if the disease gets worse or intolerable side effects occur.

Your participation on the study will be over once you have completed the end-of-study visit and the follow-up call.

End-of-Study Visit:

After your last dose of study drug, you will have an end-of-study visit. At this visit, the following tests and procedures will be performed:

* You will have a physical exam.
* You will be asked about any treatments you may have had, any other drugs you may be taking, and any side effects you may be having.
* Blood (about 2 teaspoons) will be drawn for routine tests.
* You will have a bone marrow aspiration performed to check the status of the disease.

Follow-Up:

About one month after your end-of-study visit, the study staff will call and ask about any side effects you may be having. This call should last about 5 minutes.

This is an investigational study. Ruxolitinib is FDA approved and commercially available for the treatment of intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera (post-PV) myelofibrosis and post-essential thrombocythemia (post-ET) myelofibrosis. Its use to treat acute leukemia is investigational.

Up to 166 patients will take part in this study. All will be enrolled at MD Anderson.

Phase I is a standard 3+3 design and will be used to determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD), and no formal evaluation of efficacy (response rate will be implemented. Patients in Phase I part who were treated at the MTD will be included toward patients assessed for response in the phase II stage.

Phase l/II Study of Ruxolitinib for Acute Leukemia

A Phase I/II Study to Determine the Safety and Efficacy of Ruxolitinib, a JAK1/JAK2 Inhibitor, in Subjects With Relapsed or Refractory Acute Leukemia

MTD defined as highest dose level at which no more than one out of six subject experiences dose limiting toxicity (DLT) during first cycle (28 days) of therapy. A non-hematologic DLT defined as a clinically significant grade 3 or 4 adverse event or abnormal laboratory value (according to Common Toxicity Criteria for Adverse Effects (CTCAE) criteria) assessed as related to study drug (and unrelated to disease progression, intercurrent illness, or concomitant medications) occurring during first 28 days on study. Participants who received at least 80% of the originally assigned doses in the first cycle were evaluable for DLT assessment of each cohort.

The MTD is defined as the highest dose level at which no more than one out of six subject experiences DLT during the first cycle (28 days) of therapy.

Response is defined as complete remission (CR) + complete remission with incomplete blood count (CRi) + Hematologic improvement (HI). Response was to be assessed for participants who were evaluated for the Phase II portion of this study. CR is absolute neutrophil count (ANC) \>/= 1x109/L and platelet count \>/= 100x109/L, absence of leukemia blast cells, normal marrow differential, and complete resolution of extramedullary disease. CRi is CR but platelets are \< 100x109/L or ANC is \<1x109/L. HI is described by the number of individual, positively affected cell lines without the use of growth factors and/or transfusions (lasting at least 4 weeks).

Incyte Corporation

M.D. Anderson Cancer Center

Phase I starting dose of Ruxolitinib 50 mg by mouth twice a day (BID) for 28 day cycle.

Ruxolitinib 50 mg BID

Ruxolitinib 100 mg BID

Ruxolitinib 200 mg BID

Total

Age, Continuous

United States

Region of Enrollment

Srdan Verstovsek, Professor, Leukemia

Number of Participants With Dose Limiting Toxicities (DLTs)

Phase I - Starting dose of Ruxolitinib 50 mg by mouth twice a day for 28 day cycle.

Phase II - MTD reached in Phase I.

Ruxolitinib: Phase I - Starting dose of 50 mg by mouth twice a day for 28 day cycle.

Phase II - MTD reached in Phase I.

Maximum Tolerated Dose (MTD) of Ruxolitinib

The study was stopped because of a lack of satisfactory clinical benefit, and did not go on to the Phase II portion. Therefore, data were not collected for this outcome measure.

Participants With a Response

Heart and Blood Diseases

Hemostatic Disorders

Blood Coagulation Disorders

Blood Platelet Disorders

Primary Myelofibrosis

Thrombocytosis

Thrombocythemia, Essential

Hemorrhagic Disorders

Vascular Diseases

Essential Thrombocythemia

Janus Kinase Inhibitors

LDE225

INC424

The purpose of this phase Ib/II clinical trial was to: a) evaluate the safety of the co-administration of LDE225 and INC424 in myelofibrosis patients and establish a maximum tolerated dose and/or Recommended Phase II dose of the combination and b) to assess the efficacy of the co-administration of LDE225 and INC424 on spleen volume reduction.

The study is considered to have been completed because the participants completed the study as per study design at the time of trial termination. If participants were already in extension phase until discontinuation criteria were met or alternative setting was available, they were considered as completed. The study was terminated due to one of the compounds being divested.

A Phase Ib/II Dose-finding Study to Assess the Safety and Efficacy of LDE225 + INC424 in Patients With MF

A Phase Ib/II, Open-label, Multi-center, Dose-finding Study to Assess the Safety and Efficacy of the Oral Combination of LDE225 and INC424 (Ruxolitinib) in Patients With Myelofibrosis

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.

A dose-limiting toxicity (DLT) was defined as an adverse event or abnormal laboratory value assessed as unrelated to disease progression, inter-current illness, or concomitant medications that met certain criteria as defined in the protocol.

Reduction in spleen volume as measured by magnetic resonance imaging/Cat Scan (MRI/CT) in Phase Ib expansion and Phase II Stage 1 patients

Plasma Concentration Time Curve: AUC0-24h: Area under the concentration-time curve from time zero to 24 hours extrapolate from AUClast\[mass x time x volume-1\]

AUC0-12h: Area under the concentration-time curve from time zero to 12 hours extrapolate from AUClast\[mass x time x volume-1\]. AUCinf: Area under the concentration-time curve from time zero to infinity with extrapolation of the terminal phase \[mass x time x volume-1\]. AUClast: Area under the concentration-time curve from time zero to the time of last measurable concentration \[mass x time x volume-1\].

Cmax: Maximum observed plasma concentration after drug administration \[mass x volume-

1\].

CL/F: Apparent total plasma clearance of drug after oral administration \[volume x time-1\]

The number of patients experiencing improvement in their bone marrow fibrosis by at least one grade and assessment of cellularity.

Phase Ib and Phase ll: Change in Pharmacodynamic Biomarkers: JAK2V617F allele burden

Summary of cytokine levels in Pharmacodynamic Biomarkers for all 26 collected at Week 25 Day 1 and Week 49 Day 1

The 7-day modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 is a 7-item PRO instrument based on the modified MFSAF v2.0 diary administered at specified visits. The first 6 items assess MF symptom severity at its worst as recalled in the 7 days prior to the clinic visit assessment. The symptoms measured include night sweats, itching, abdominal discomfort, pain under the ribs (left side), early satiety, \& bone/muscle pain. The 7th item captures MF-related inactivity in the past 7 days prior to the clinic visit assessment. All 7 items ask subjects to record their answers on an 11-point numeric rating scale (NRS), (0 = Absent, 10 = Worst Imaginable). The first 6 items of the instrument focus on MF symptoms \& are summed to create a Total Symptom score.

EORTC QLQ-C30 is the European Organization for Research \& Treatment of Cancer, Quality of Life (QoL) Questionnaire \& is one of the most widely used \& validated instruments to measure health-related QoL in subjects with cancer. The scale includes 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning \& social functioning), global health status/QoL \& 9 symptom scale/items (fatigue, nausea \& vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, \& financial difficulties). This instrument asks the subject to respond according to the past week, with the exception of the first 5 questions that represent physical functioning \& capture the subject's current status. The range of scores for all of the scales is from 0 to 100. For functional \& global health status/QoL scales, higher scores indicate better QoL \& level of functioning; for symptom scales, higher scores indicate greater level of symptoms or difficulties.

Racc: Accumulation ratio calculated as AUC0-12h on Week 9 Day 1 divided by AUC0-12h on Week 1 Day 1 \[fold\]

T1/2: Elimination half-life associated with the terminal slope (lambda_z) of a semi logarithmic concentration-time curve \[time\]

Vss/F: Apparent volume of distribution at steady state after oral administration \[volume\]

Participants who took a combination of LDE225 400mg and INC424 10mg in the dose escalation phase

LDE225 400 mg + INC424 10 mg

Participants who took a combination of LDED225 400mg and INC424 15mg in the dose escalation phase

LDE225 400 mg + INC424 15 mg

Participants who took a combination of LDED225 400mg and INC424 20mg in the dose escalation phase

LDE225 400 mg + INC424 20 mg

Participants who took a combination of LDED225 400mg and INC424 20mg in the dose expansion phase

LDE225 400 mg + INC424 20 mg (Dose Expansion)

Participants who took a combination of LDE225 400mg and INC424 10mg in the dose escalation phase.

LDE225 400mg + INC424 10 mg (Dose Escalation Phase)

LDE225 400mg + INC424 15 mg (Dose Escalation Phase)

Participants who took a combination of LDE225 400mg and INC424 20mg in the dose escalation phase.

LDE225 400mg + INC424 20mg (Dose Escalation Phase)

LDED225 400mg + INC424 20mg (Dose Expansion Phase)

Race (NIH/OMB)

Please refer to detailed description regarding reason for early termination of study.

LDE225 400mg + INC424 10mg (Dose Escalation Phase)

LDE225 400mg + INC424 15mg (Dose Escalation Phase)

Safety Analysis Set (SAS) included all participants in Phase Ib \& Phase II who received at least 1 dose of LDE225 and/or INC424 \& had at least 1 valid post-baseline safety assessment. DLT was measured in the Phase Ib dose escalation \& expansion phase, as part of the primary outcome. All participants in the safety set were considered for toxicities.

Number of Participants With Dose Limiting Toxicities (DLTs) (Phase 1b)

The Full Analysis Set (FAS) comprised all subjects in Phase Ib and Phase II who received at least one dose of LDE225 and/or INC424. The data disclosed includes only participants from Phase Ib dose expansion phase and Ph II Stage 1. This data does not include dose escalation Phase Ib participants.

Percentage of Patients Achieving >= 35% Reduction in Spleen Volume in Phase Ib Expansion and Phase II Stage 1

LDE225 (Week 1, Day 1) (n=6,10,4,24)

LDE225 (Week 9, Day 1) (n=6,6,4,14)

The Pharmacokinetic Analysis set (PAS) consisted of all subjects in Phase Ib and Phase II who received at least one (full or partial) dose of LDE225 and/or INC424 and provided at least one evaluable PK blood sample for LDE225 and/or INC424.

Phase Ib and Phase II: LDE225: Plasma Pharmacokinetics (PK) Parameter: Area Under the Curve(AUC0-24h)

AUC0-12h: Wk1 Day 1 (n=8,10,5,25)

AUC0-12h: Wk 9 Day 1 (n=8,9,4,20)

AUCinf: Wk1 Day 1 (n=7,9,4,16)

AUCinf: Wk 9 Day 1 (n=8,9,3,15)

AUClast: Wk1 Day 1 (n=8,10,5,26)

AUClast: Wk 9 Day 1 (n=8,9,4,20)

Phase Ib and Phase II: INC424: PK Parameters: Area Under the Curve for AUC0-12h, AUCinf & AUClast

LDE225 (Week 1, Day 1) (n=6,10,5,26)

LDE225 (Week 9, Day 1) (n=8,8,5,20)

INC424 (Week 1, Day 1) (n=8,10,5,27)

INC424 (Week 9, Day 1) (n=8,9,4,20)

The pharmacokinetic analysis set (PAS) consisted of all subjects in Phase Ib and Phase II who received at least one (full or partial) dose of LDE225 and/or INC424 and provided at least one evaluable PK blood sample for LDE225 and/or INC424.

Phase Ib and Phase II: LDE225 & INC424: PK Parameter: Maximum Plasma Concentration (Cmax)

Phase Ib and Phase II: LDE225 & INC424: Plasma PK Parameter: Time to Maximum Plasma Concentration (Tmax)

LDE225 (Week 1, Day 1) (n=5,5,1,12)

INC424 (Week 1, Day 1) (n=7,9,4,16)

INC424 (Week 9, Day 1) (n=0,0,0,0)

Phase Ib and Phase II: LDE225 & INC424:: Plasma Pharmacokinetics (PK) Parameters: Area Under the Curve(CL/F)

Baseline, grade 0 (n=0,0,0,1)

Baseline, grade 1 (n=0,1,0,4)

Baseline, grade 2 (n=4,6,3,8)

Baseline, grade 3 (n=3,3,0,8)

Baseline, missing grade (n=1,0,2,6)

Week 25 Day 1, grade 1 (n=1,1,0,1)

The Full Analysis Set (FAS) comprised all subjects in Phase Ib and Phase II who received at least one dose of LDE225 and/or INC424.

Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
MAP to Provide Access to Ruxolitinib, for Patients With Polycythemia Vera	NCT05269771	Polycythemia Ve...	Ruxolitinib	12 Years - 99 Years	Novartis
Expanded Treatment Protocol (ETP) of Ruxolitinib in Patients With Polycythemia Vera Who Were Hydroxyurea Resistant or Intolerant and for Whom no Treatment Alternatives Was Available.	NCT02292446	Polycythemia Ve...	Ruxolitinib	18 Years -	Novartis
Phase l/II Study of Ruxolitinib for Acute Leukemia	NCT01251965	Leukemia	Ruxolitinib	14 Years -	M.D. Anderson Cancer Center
A Phase Ib/II Dose-finding Study to Assess the Safety and Efficacy of LDE225 + INC424 in Patients With MF	NCT01787552	Primary Myelofi... Thrombocytosis Essential Throm... Polycythemia Ve... Myeloproliferat... Bone Marrow Dis... Hematologic Dis... Blood Coagulati... Blood Platelet ... Hemorrhagic Dis...	LDE225 INC424	18 Years -	Novartis
Ruxolitinib Efficacy and Safety in Patients With HU Resistant or Intolerant Polycythemia Vera vs Best Available Therapy.	NCT02038036	Polycythemia Ve...	Best Available ... Ruxolitinib	18 Years -	Novartis
Ruxolitinib Efficacy and Safety in Patients With HU Resistant or Intolerant Polycythemia Vera vs Best Available Therapy.	NCT02038036	Polycythemia Ve...	Best Available ... Ruxolitinib	18 Years -	Novartis
Ruxolitinib for Patients With Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)	NCT01895842	Leukemia	Ruxolitinib	18 Years -	M.D. Anderson Cancer Center
CINC424A2X01B Rollover Protocol	NCT02386800	Primary Myelofi... Polycythemia Ve... Graft Versus Ho... Acute Myeloid L... Thalassemia	ruxolitinib panobinostat	1 Month -	Novartis
Asian Phase II Study of INC424 in Patients With Primary Myelofibrosis (MF), Post-PV MF or Post-ET MF	NCT01392443	Primary Myelofi... Post-Polycythem... Post-Essential ...	Ruxolitinib	18 Years - 65 Years	Novartis
Ruxolitinib for Patients With Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)	NCT01895842	Leukemia	Ruxolitinib	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for inc424

Every month we try and update this database with for inc424 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for inc424

Every month we try and update this database with for inc424 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for inc424 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.