Neoplasms

Blood and Lymph Conditions

All Conditions

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

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

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Imatinib Mesylate

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Imatinib

Novartis

This study will assess the safety and efficacy of imatinib in newly enrolled previously untreated patients with chronic phase CML.

Efficacy, Safety and Long-term Prognosis of Imatinib in Patients Newly Diagnosed With Chronic Myelogenous Leukemia (Chronic Phase)

External Affairs

Philadelphia Chromosome

Nilotinib

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

Asciminib

Patients will receive asciminib (40 mg BID continuous)

Patients will receive best available therapy chosen by investigator

Asciminib comes in 20 mg and 40 mg tablets and is taken orally twice daily

asciminib

Best available treatment will be based on investigator's choice identified prior to randomization. Dose and frequency will depend on label and institutional guidelines for various BAT

best available treatment

The purpose of this Chinese bridging study is to evaluate the efficacy, safety, tolerability and pharmacokinetics of asciminib versus best available therapy in Chinese patients with Chronic Myelogenous Leukemia in chronic phase, previously treated with 2 or more tyrosine kinase inhibitors to support related indication registration in China.

The primary objective of the study is to evaluate the Major Molecular Response (MMR) rate of asciminib treatment at 24 weeks.

The purpose of this Chinese bridging study is to evaluate the efficacy, safety, tolerability and pharmacokinetics (PK) of asciminib versus best available therapy (BAT) in Chinese patients with Chronic Myelogenous Leukemia in chronic phase (CML-CP), previously treated with 2 or more tyrosine kinase inhibitors (TKIs) to support related indication registration in China.

This study will enroll the participants 1) who failed their most recent TKI therapy by meeting the definition of treatment failure as per the 2013 European Leukemia Net (ELN) guidelines, or 2) who were intolerant to the most recent TKI therapy and must have BCR-ABL1 ratio \> 0.1% IS at screening.

Eligible participants will be randomized into asciminib arm or the BAT arm on a 2:1 ratio, to receive asciminib treatment (continuous 40 mg BID) or BAT from Day 1 until the end of study treatment period defined as 96 weeks after the last participant receives the first dose.

Study of Efficacy and Safety of CML-CP Patients Treated With Asciminib Versus Best Available Therapy, Previously Treated With 2 or More Tyrosine Kinase Inhibitors

A Randomized, Open-label, Multi-center, Phase II Study of Asciminib Versus Best Available Therapy in Chinese Patients With Chronic Myelogenous Leukemia in Chronic Phase (CML-CP), Previously Treated With 2 or More Tyrosine Kinase Inhibitors

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

Evaluate the major molecular response rate at 24 weeks in asciminib arm

Evaluate the cytogenetic response rate (Complete, Partial, Major, Minor, Minimal, no response) at and by all scheduled data collection time points including 24, 48 and 96 weeks for both asciminib arm and best available treatment arm.

Evaluate the major molecular response rate at week 24 of best available treatment arm, and compare with asciminib arm

Evaluate the major molecular response rate, collected at all scheduled data collection time point (except week 24)

Evaluate the major molecular rate by all scheduled data collection time points including 24, 48 and 96 weeks by treatment group

Evaluate the time from the date of the first dose of study drug to the date of the first documented MMR by treatment group

First document major molecular response to loss of MMR up to 96 weeks after last participant receive the first dose

To evaluate the time from the date of randomization to the date of death (including the survival follow-up period)

Evaluate the time from the date of randomization to the earliest occurrence of documented disease progression to AP/BC or the date of death from any cause (including progressions and deaths observed during the survival follow-up period)

Characterize PK of asciminib in the Chinese CML-CP population. Cmax is the maximum (peak) observed plasma drug concentration after dose administration (ng/mL).

Characterize PK of asciminib in the Chinese CML-CP population. Tmax is the time to reach maximum (peak) plasma drug concentration after dose administration (hr).

Characterize PK of asciminib in the Chinese CML-CP population. Trough plasma concentrations (Ctrough)

Characterize PK of asciminib in the Chinese CML-CP population. The partial area under the plasma concentration-time curve from dose time to tau (ng\*hr/mL). For a bid regimen, Tau=12h.

Characterize PK of asciminib in the Chinese CML-CP population. AUClast is the The AUC from the time of dosing to the time of the last measurable plasma concentration (Tlast) (ng\*hr/mL)

Participants received 300 mg twice daily (b.i.d.). Dose increases to 400 b.i.d. were permitted, per Investigator's discretion.

Nilotinib was supplied as 150 mg and 200 mg hard gelatin capsules.

"This is a single-arm, open-label, multi-center study of complete molecular response (CMR) in adult patients with newly diagnosed Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia in chronic phase (CML-CP). The study is designed to evaluate early and deep molecular responses up to 4 years on nilotinib treatment. The primary end point is Rate of confirmed CMR in newly diagnosed Philadelphia chromosome positive CML-CP patients."

CMR Rate of Newly Diagnosed CML-CP Patients Treated With Nilotinib

A Single-arm, Open-label, Multi-center Study of Complete Molecular Response (CMR) in Adult Patients With Newly Diagnosed Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)

CMR was defined as at least 4.5 log reduction of breakpoint cluster region gene/Abelson proto-oncogene (Bcr-Abl) transcipts from the standardized baseline on the international scale (equivalent to Bcr-Abl \<=0.0032% IS) with a minimum of 25,614 ABL control copies. CMR was to be confirmed by a second polymerase chain reaction (PCR) sample drawn 3 months later where the results should be less than or equal to 0.0032% with a minimum of 25,614 Abelson proto-oncogene (ABL) control copies.

CCyR was defined as 0% Philadelphia chromosome-positive (Ph+) metaphases in the bone marrow. MMR was defined as a 3 log reduction of Bcr-Abl transcripts from the standardized baseline on the international scale (equivalent to Bcr-Abl ≤ 0.1% IS).

Bcr-Abl transcripts assessed by peripheral blood quatitative real time polymerase chain reaction (RQ-PCR) were used for the determination of all molecular responses.

Time to CMR, CCyR, and MMR was defined as the time from the date of enrollment to the date of first documented CMR, CCyR and MMR, respectively.

Duration of CMR, CCyR and MMR were defined as the time from the first date of achievement of the response to the date of first documented loss of the response.

Progression to AP/BC is defined as loss of CCyR, MMR, and CMR and was summarized by frequencies and percentages.

Time to progression of AP/BC was defined as the time from the date of the first dose of study drug to the date of first documented progression of AP/BC.

Rate of loss of CMR was defined as an increase in the Bcr-Abl transcripts to greater than 0.0032% IS. Rate of loss of CCyR was defined as an increase in the Ph+ bone marrow cells to greater than 0%. Rate of loss of MMR was defined as an increase in the Bcr-Abl transcripts to greater than 0.1% IS.

Event-free survival was defined as the time from the date of enrollment to the date of first occurrence of any of the following: loss of Complete Hematological Response (CHR), loss of CCyR, loss of Partial Cytogenetic Response (PCyR), progression to the accelerated phase or blast crisis, and death from any cause. Progression-free survival was defined as the time from the date of enrollment to the date of first occurrence of any of the following: progression to the accelerated phase or blast crisis, death, and loss of CMR. Overall survival was defined as the time from the date of enrollment until death due to any cause.

Age, Continuous

Sex: Female, Male

Study Director

Full Analysis Set (FAS): The FAS included all randomized participants who received at least one dose of study drug.

Number of Participants With Confirmed Complete Molecular Response (CMR)

CCyR

Number of Participants With Complete Cytogenetic Response (CCyR) and Major Molecular Response (MMR)

CMR (n=34)

CCyR (n=93)

MMR (n=94)

Of the 128 participants analyzed, 34 participants achieved CMR within 18 months of treatment, 93 participants achieved CCyR and did not experience loss of CCyR during the study, and 94 participants achieved MMR with up to 24 months of treatment (most achieved MMR within 12 months of treatment).

Time to CMR, CCyR and MMR

Duration of CMR, CCyR and MMR

Number of Participants With Progression to Accelerated Phase/Blastic Crisis (AP/BC)

Of the 128 participants analyzed, 1 participant experienced progression to AP/BC.

Time to Progression of AP/BC

Numbers are based on the total number of participants who achieved and experienced loss of CMR (34 participants), CCyr (93 participants) and MMR (94 participants), respectively.

Number of Participants With Loss of CCyR, MMR and CMR

Of the 128 participants analyzed, 3 participants received an escalated dose of 400 mg b.i.d.

Number of Participants With CMR Who Were Dosed to 400 mg b.i.d.

Event-free

Progression-free

Overall

Event-free Survival, Progression-free Survival and Overall Survival

Overall Study

Immune System Diseases

Heart and Blood Diseases

Syndrome

Anemia

Lymphoma

Multiple Myeloma

Neoplasms, Plasma Cell

Recurrence

Leukemia, Lymphoid

Hematologic Neoplasms

Anemia, Aplastic

Leukemia, Myeloid, Acute

Leukemia, Lymphocytic, Chronic, B-Cell

Hodgkin Disease

Polycythemia Vera

Polycythemia

Preleukemia

Myelodysplastic Syndromes

Primary Myelofibrosis

Blast Crisis

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Precancerous Conditions

Leukemia, B-Cell

Bone Marrow Failure Disorders

Pancytopenia

Lymphosarcoma

Acute Myeloid Leukemia

Aplastic Anemia

Acute Non Lymphoblastic Leukemia

Chronic Lymphocytic Leukemia

Hodgkin Lymphoma

Acute Graft Versus Host Disease

Fludarabine

Fludarabine phosphate

Melphalan

Alemtuzumab

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

Fludarabine 30 mg/m2 intravenously daily at the same time over 30 minutes on days -7,-6,-5,4,-3,.

Stem cells

Campath, 20 mg IV on day -7, 6, -5, -4, and -3.

Campath

Andrew Artz, MD

Objectives:

1. To evaluate disease free survival after Campath 1H-based in vivo T-cell depletion and non-myelo-ablative ablative stem cell transplantation in patients with hematologic malignancies.
2. To evaluate the incidence and severity of acute and chronic GVHD after Campath 1H-based in vivo T-cell depletion, in patients with hematologic malignancies undergoing non-myelo-ablative stem cell transplantation.
3. To evaluate engraftment and chimerism after Campath 1H-based in vivo T-cell depletion and non-myelo-ablative ablative stem cell transplantation in patients with hematologic malignancies.

T-Cell Depleted Allogeneic Stem Cell Transplantation for Patients With Hematologic Malignancies

All patients were administered the following drugs;

1. Fludarabine 30mg/m2 intravenously daily at the same time over 30 min on days -7,-6,-5,-4, and -3
2. Melphalan 140mg/m2 IV on day -2
3. Stem cell infusion on day 0
4. Campath 20mg IV on day -7,-6,-5,-4, and -3

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Efficacy, Safety and Long-term Prognosis of Imatinib in Patients Newly Diagnosed With Chronic Myelogenous Leukemia (Chronic Phase)	NCT00237120	Chronic Myeloge...	Imatinib	15 Years - 74 Years	Novartis
Nilotinib, for Patients With CML-CP or CML-AP	NCT04518644	Chronic Myeloge...	Nilotinib	18 Years - 99 Years	Novartis
Study of Efficacy and Safety of CML-CP Patients Treated With Asciminib Versus Best Available Therapy, Previously Treated With 2 or More Tyrosine Kinase Inhibitors	NCT04795427	Leukemia, Chron...	asciminib best available ...	18 Years -	Novartis
Nilotinib, for Patients With CML-CP or CML-AP	NCT04518644	Chronic Myeloge...	Nilotinib	18 Years - 99 Years	Novartis
CMR Rate of Newly Diagnosed CML-CP Patients Treated With Nilotinib	NCT01227577	Chronic Myeloge...	Nilotinib	18 Years -	Novartis
T-Cell Depleted Allogeneic Stem Cell Transplantation for Patients With Hematologic Malignancies	NCT00683046	Acute Myelogeno... Lymphoid Leukem... Chronic Myeloge... Malignant Lymph... Hodgkin's Disea... Chronic Lymphoc... Myeloproliferat... Anemia, Aplasti... Myelodysplastic...	Fludarabine Melphalan Stem cells Campath	- 100 Years	University of Chicago
T-Cell Depleted Allogeneic Stem Cell Transplantation for Patients With Hematologic Malignancies	NCT00683046	Acute Myelogeno... Lymphoid Leukem... Chronic Myeloge... Malignant Lymph... Hodgkin's Disea... Chronic Lymphoc... Myeloproliferat... Anemia, Aplasti... Myelodysplastic...	Fludarabine Melphalan Stem cells Campath	- 100 Years	University of Chicago

Spots Global Cancer Trial Database for chronic myelogenous leukemia in chronic phase