Neoplasms

Blood and Lymph Conditions

All Conditions

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Philadelphia Chromosome

Neoplasms by Histologic Type

Hematologic Diseases

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Disease Attributes

Myeloid Leukemia

Chronic Graft Versus Host Disease

Chronic Myeloid Leukemia

Chronic Myeloproliferative Disorders

All Drugs and Chemicals

Antineoplastic Agents

Amino Acids

Nilotinib

Imatinib Mesylate

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

The recommended dosing of nilotinib is 400 mg orally twice daily

The purpose of this Cohort Treatment Plan is to allow access to Nilotinib for eligible patients diagnosed with imatinib-intolerant and/or resistant Philadelphia Chromosome positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) or Chronic Myelogenous Leukemia in Accelerated Phase (CML-AP). The patient's Treating Physician should follow the suggested treatment guidelines and comply with all local health authority regulations.

Nilotinib, for Patients With CML-CP or CML-AP

Managed Access Program to Provide Access to Nilotinib, for Patients With Imatinib-intolerant and/or Resistant Ph+ Chronic Myelogenous Leukemia (CML) in Chronic Phase or CML in Accelerated Phase

Novartis Pharmaceuticals

Translocation, Genetic

Chromosome Aberrations

The planned dose of nilotinib 400 mg b.i.d (twice a day) was selected for the combination as this is the dose approved for the treatment of the patient population that will be included in the present study. The starting dose for LDE225 chosen for the current study is 400 mg once daily(q.d.). The maximum dose of LDE225 that will be tested in combination with nilotinib is 800 mg once dail.y

Nilotinib is an aminopyrimidine ATP-competitive inhibitor of the protein tyrosine kinaseactivity of BCR-ABL.

Nilotinib + LDE225

The purpose of this study is to determine the feasibility of administering the combination of nilotinib and LDE225 to patients with chronic or accelerated phase of chronic myeloid leukemia and to establish the maximum tolerated dose (MTD) and/or recommended Phase II dose level (RP2D) of LDE225 in combination with nilotinib.

Nilotinib and LDE225 in the Treatment of Chronic or Accelerated Phase Myeloid Leukemia in Patients Who Developed Resistance to Prior Therapy

A Single-arm Dose-finding Phase Ib Multicenter Study of the Oral Smoothened Antagonist LDE225 in Combination With Nilotinib in Chronic or Accelerated Phase of Chronic Myeloid Leukemia Patients Who Have Failed Prior Therapy With Other BCR-ABL Tyrosine-kinase Inhibitors

Determination of the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of nilotinib in combination with LDE225

Assessment of the safety and tolerability profile of nilotinib in combination with LDE225

Assessment of the PK characteristics of nilotinib administered in combination with LDE225

Determination of the kinetics of major molecular response

Determination of the kinetics of complete molecular response

Determination of major cytogenetic response rates

Determination of complete cytogenetic response rates

All patients will receive nilotinib 300mg bid po daily. Nilotinib dose is taken every 12 hours

nilotinib

This study is to determine the number of European Leukemia Network (ELN)guideline defined treatment failure events from time of study entry in CML-CP patients with low imatinib trough concentrations treated with nilotinib.

Study of Nilotinib in Ph+ CML-CP Patients With Low Imatinib Trough Plasma Concentrations

A Multi-center, Single Arm Study of Nilotinib in Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) Patients With Low Imatinib Trough Plasma Concentrations

Treatment failure events from time of study entry in Complete molecular response-Chronic phase (CML-CP) participants with low imatinib trough concentrations less than 850 nanogram per milliliter (\<850 ng/mL) treated with nilotinib as defined in European LeukemiaNet (ELN)-guideline.

Complete Cytogenetic Response (CCyR) is defined as 0% of Ph+ metaphases. A patient was counted as CCyR at 12 cycles if the patient met the CCyR criteria at the Cycle 12 Visit.

Major molecular response is defined as values equal or below 0.1% on the International Scale.

Complete Molecular Response is defined as a Bcr-Abl (a fusion of gene of Bcr and ABl genes) ratio ≤0.0032% on the International Scale Bcr = breakpoint cluster gene Abl = abelson proto-oncogene.

Durations of major/complete cytogenetic response is defined as the time from the first documentation of the major/ complete response to the first documentation of the disease progression.

Event-free survival was defined as the time from the date of randomization to the date of first occurrence of any of the following events on study treatment: loss of complete hematological response, confirmed loss of complete cytogenetic response (CCyR), confirmed loss of major molecular response (MMR), death from any cause during treatment, progression to the accelerated phase or blast crisis of chronic myelogenous leukemia (CML) per European Leukemia Network (ELN) criteria, whichever was earliest.

Progressions free survival is defined as time between Day 1 cycle 1 and time to first documented disease progression or death. Disease progression will be determined as per response criteria.

Overall survival time is defined as the time from the treatment start to the date of death due to any reason.

An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury.

Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical examination or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.

Participants received nilotinib 300 mg, BID po, every 12 hours in continuous 28-day cycle up to 2 years.

Age, Categorical

Sex: Female, Male

Caucasian

Race/Ethnicity, Customized

The study was terminated early due to slow enrollment.

Study Director

The overall number of participants considered for analysis was "0" due to the premature termination of the study and low enrollment; The efficacy and quality of life assessments were not collected and reported in the study.

Number of Treatment Failure Events up to 2 Years

European LeukemiaNet (ELN)-Defined Optimal Responses

Loss of Complete Cytogenetic Response (CCyR), Major Molecular Response (MMR) and Complete Molecular Response (CMR) on Nilotinib

Duration of Complete Cytogenetic Response (CCyR), Major Molecular Response (MMR) and Complete Molecular Response (CMR)Achieved on Nilotinib

Event-free Survival (EFS), Progression-free Survival (PFS) and Overall Survival (OS) up to 2 Years

European LeukemiaNet (ELN)-Defined Suboptimal Events

Number of Participants Reported Adverse Events

Participants received nilotinib 300 milligram (mg) twice daily (bid) through the mouth (po), every 12 hours in a continuous 28-day cycle up to 2 years.

Overall Study

administered orally at a dose of 300 mg twice daily for 24 months

The study was a local multicentric, open-label, non-randomized phase II study of nilotinib as a first line treatment in adult patients with newly-diagnosed Philadelphia chromosome-positive (Ph+) and chronic phase myeloid leukemia (CML-CP).

This was a multicenter, open-label, single-arm, phase 2 study of nilotinib as a frontline treatment for patients with Ph+ CMLCP. All patients received oral nilotinib 300 mg twice daily for a planned treatment duration of 24 months or until early discontinuation.

The primary efficacy end point was the cumulative rate of Major Molecular Response (MMR) in all participants by 12 months. Secondary efficacy end points included the rate of Complete Cytogenic Response (CCyR) at 6 and 12 months; cumulative rates of MMR up to 24 months; time to and durability of MMR; and cumulative rate of Complete Haematologic Response (CHR) by 12 months.

Patient evaluations, including hematologic assessments, were conducted every 15 days during the first 3 months, monthly until month 12, and then every 3 months until the end of the study (24 months). All efficacy analyses were performed in the intent-to treat population.

Study of Nilotinib as First Line Treatment in Philadelphia Chromosome Positive(Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)

A Phase II Multi-center, Open-label, Non-randomized Study of Nilotinib as First Line Treatment in Adult Patients With Newly Diagnosed Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)

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 review 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 availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Major Molecular Response (MMR) was defined as BCR-ABL1\^IS ≤0.1%, on the International Scale \[BCR-ABL1IS\]) by 12 months. BCR is the Breakpoint Cluster Region gene / BCR gene product and ABL is the Abelson proto-oncogene. BCR-ABL is the Fusion gene from BCR and ABL/Protein product from BCR-ABL. Participants who withdrew prematurely or those who failed to provide data for the study for other reasons were designated as premature withdrawal or inevaluable, respectively, and were included in the ITT analysis as non-responders.

CCyR rate is identified as the rate of patients who had 0% of Ph+ metaphase.

A confirmed complete hematological response (CHR) is defined when all of the following criteria are achieved: WBC \<10 x 109/L, thrombocyte \<450 x 109/L, myelocyte + metamyelocyte \<%5 in blood, no sign of blast and promyelocyte in blood, basophil \<%5, and no sign of extramedullary involvement.

Time to MMR is defined as the time period from the date of first dose intake until the first documented MMR.

MMR duration is defined as the time from the date of first documented MMR to the first time of the lost MMR, progression or death.

Age, Continuous

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

Percentage of Participants Who Achieved Major Molecular Response (MMR) During the First 12 Months

3 months

6 months

9 months

15 months

18 months

21 months

24 months

Percentage of Participants Who Achieved Major Molecular Response (MMR) up to 24 Months

Month 6

Month 12

ITT analysis set included only the participants who had measurements i.e. excluding drop outs.

Percentage of Participants With Complete Cytogenetic Response (CCyR) at Month 6 and 12

Month 3

Month 9

Month 18

Month 24

Percentage of Participants With Complete Hematologic Response (CHR) at Month 3, 6, 9, 12, 18 and 24

ITT analysis set. Only participants with a MMR were included in the analysis

Time to Major Molecular Response (MMR)

ITT analysis set. Only participants with a MMR and subsequent loss of MMR were included in the analysis

Duration of Major Molecular Response (MMR)

Immune System Diseases

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Lymphosarcoma

Antipyretics

Anti-Inflammatory Agents

Antirheumatic Agents

Fibrinolytic Agents

Analgesics

Platelet Aggregation Inhibitors

Lipid Regulating Agents

Aspirin

Ponatinib

Hydroxymethylglutaryl-CoA Reductase Inhibitors

Treatment:

Patients will receive daily oral administration of Ponatinib at a dose of 45 mg/day for 6 weeks (defined as one course) for 8 courses, same dose and schedule, for a total of 48 weeks. Each patient will be followed for the subsequent 24 months, every 3 month, providing survival information and monitoring serious adverse event. Each patient should be treated for a minimum of 6 weeks. Patients must be discontinued from the trial in the event of myocardial infarction or stroke, or for development or progression of arterial disease necessitating revascularization. Once a complete hematologic response has been achieved, with a platelet count ≥ 50x109/L, patients can be treated with aspirin and/or a statin as clinically indicated, at investigator discretion.

Michele Baccarani, Pr.

Drug resistance resulting from emergence of Imatinib-resistant BCR-ABL clones is a significant problem in Ph positive ALL patients because after a very good initial response to one TKI inhibitor, many patients relapse within one year, relapse being almost always associated with a BCR-ABL kinase domain point mutation. The patients who relapse after treatment with one TKI can be rescued to remission with another TKI, but the second remission is usually shorter than the previous one. A more potent TKI inhibitor, and pan-active not only on all the BCR-ABL variants (including the second generation TKI resistant T315I mutant), but also on others molecular targets can do better. In this context, Ponatinib is a novel synthetic orally active tyrosine kinase inhibitor (TKI), specifically developed to inhibit BCR-ABL, the fusion protein that is the product of the Philadelphia chromosome (Ph) in chronic myeloid leukemia (CML) and in a subset of acute lymphoblastic leukemia (Ph+ ALL). It potently inhibits the BCR-ABL protein as well as mutated forms of the protein that arise in patients resistant to prior therapies with TKIs. Ponatinib has been demonstrated to inhibit all the mutations that have been detected so far, in vitro and in vivo and to uniformly suppress the emerge of single-mutant clones in a mutagenesis assay. In the Phase II study, 41% of Philadelphia chromosome positive acute lymphoblastic leukemia patients treated with Ponatinib achieved major hematologic response, 47% had a major cytogenetic response, 38% obtained a complete cytogenetic response, showing that Ponatinib provides significant benefit despite previous intolerance or refractoriness to other TKIs. The Phase I trial showed that patients with a more recent diagnosis had increased rates of major molecular response: 79% for 14 patients with 0 to 5 years since diagnosis vs. 29% for 14 patients with more than 5 to 9 years since diagnosis (P=0.02) and 27% for 15 patients with more than 9 to 24 years since diagnosis (P=0.009). These characteristics support the hypothesis for a role of Ponatinib not only in patients resistant to prior TKI therapy but also in untreated ALL Ph+ patients, in order to prevent the emergence of resistant caused by the selection of mutated Ph+ clones and in order to avoid rapid progression of the disease.

This is a multi-center, phase 2, single arm unblinded trial of oral Ponatinib in patients with Ph+ Acute Lymphoblastic Leukemia. Patients will receive daily oral administration of Ponatinib at a dose of 45 mg/day for 6 weeks (defined as one course) for 8 courses, same dose and schedule, for a total of 48 weeks. Each patient will be followed for the subsequent 24 months, every 3 month, providing survival information and monitoring serious adverse event.

Each patient should be treated for a minimum of 6 weeks. Then a patient can be discontinued in the following situation:

* at the end of first course (6 weeks), in case of lack of CHR;
* at the end of third course (18 weeks), in case of lack of CCgR;
* any time in case of loss of CHR or CCgR.

If they remain on therapy after 48 weeks, they will be able to continue treatment during the extension phase of the study, if it is of interest of the patient, or they will be allowed to receive any treatment that is in their interest. For all the patients remaining on trial, response, outcome and toxicity will be followed for the subsequent 24 months.The 6-weeks periodicity must be rigidly respected, irrespective of the temporary discontinuation of study drug (eg, if a patient will take Ponatinib only for 4 weeks and will remain off-treatment for the subsequent two weeks because of AE, when the 7th week begins this patient will restart Ponatinib as a second course, as per protocol). Prednisone (P) will be administered to all patients for 7-14 days, before Ponatinib, so as to make it possible to wait for the results of cytogenetic and molecular tests, and to evaluate the response to P alone, hence for another 21 days. Intrathecal therapy (IT) with MTX/AraC/DEX is mandatory, every 28 days, in patients without clinical-cytologic evidence of meningeal involvement. In patients with CNS disease, IT is performed twice weekly until a complete clearance of cerebrospinal fluid blast cells is achieved, hence once weekly for 4 weeks, hence once monthly.

Phase II Front-line Ponatinib in Adult Philadelphia+/BCR-ABL+ Acute Lymphoblastic Leukemia.

Front-line Treatment of Philadelphia Positive/BCR-ABL Positive Acute Lymphoblastic Leukemia With Ponatinib, a New Potent Tyrosine Kinase Inhibitor.

The primary endpoint is the proportion of patients who are in CHR at 6 months, calculated on the total number of patients who have been enroled and have received at least one dose of the first drug (prednisone).

CHR requires that all of the following are present:

* Bone marrow with less than 5% blast cells
* Peripheral blood differential without blasts
* PMN ≥ 1.5 x 109/L
* PLT ≥ 100 x 109/L
* No evidence of extramedullary involvement from leukemia

CgR is defined based on the percentage of Ph pos metaphases, as evaluated by chromosome banding analysis (CBA) of at least 20 marrow cell metaphases:

1. Complete (CCgR) if Ph pos 0
2. Partial (PCgR) if Ph pos 1-34%
3. Minor (mCgR) if Ph pos 35-65%
4. Minimal or none (min/none CgR) if Ph pos \> 65% If only interphase FISH data are available, the response can be defined only as non-complete or complete - to be complete by FISH, it is required that less than 1% of nuclei (minimum number 200) have a positive signal.

Duration of CCgR is measured by the date of the achievement of CCgR to the date of CCgR loss.

Molecular response is classified as:

• Complete if by RT-Q-PCR the BCR-ABL: ABL ratio is below 0.01, with a sensitivity of at least 30,000 molecules of ABL.

Molecular response (MR) is classified as:

• Major (MMolR) if by RT-Q-PCR the BCR-ABL: ABL ratio is lower than 0.10, with a sensitivity of at least 30,000 molecules of ABL.

Duration of CMR is measured by the date of the achievement of CMR to the date of CMR loss.

Events are induction failure, relapse and death whichever comes first.

Overall survival is measured in all patients from the data of enrolment to the date of death, by any causes.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Nilotinib, for Patients With CML-CP or CML-AP	NCT04518644	Chronic Myeloge...	Nilotinib	18 Years - 99 Years	Novartis
Nilotinib and LDE225 in the Treatment of Chronic or Accelerated Phase Myeloid Leukemia in Patients Who Developed Resistance to Prior Therapy	NCT01456676	Philadelphia Ch...	Nilotinib + LDE...	18 Years -	Novartis
Nilotinib, for Patients With CML-CP or CML-AP	NCT04518644	Chronic Myeloge...	Nilotinib	18 Years - 99 Years	Novartis
Study of Nilotinib in Ph+ CML-CP Patients With Low Imatinib Trough Plasma Concentrations	NCT01131325	CML Philadelphia Ch... Chronic Myeloge...	nilotinib	18 Years -	Novartis
Study of Nilotinib as First Line Treatment in Philadelphia Chromosome Positive(Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)	NCT01274351	Chronic Myeloge...	Nilotinib	18 Years -	Novartis
Phase II Front-line Ponatinib in Adult Philadelphia+/BCR-ABL+ Acute Lymphoblastic Leukemia.	NCT01641107	Philadelphia Po... BCR-ABL Positiv... Acute Lymphobla...	Ponatinib	18 Years -	Incyte Corporation

Spots Global Cancer Trial Database for ph+

Every month we try and update this database with for ph+ 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 ph+

Every month we try and update this database with for ph+ 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 ph+ 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.