Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Philadelphia Chromosome

Lymphoma

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Lymphosarcoma

Antineoplastic Agents

All Drugs and Chemicals

Vincristine

Tubulin Modulators

Antimitotic Agents

Eligible subjects received study drug at 2.25 mg/m\^2 intravenously via peripheral or central venous access over 60 minutes (± 10 minutes).

Dosing was done every 7 days (± 3 days) on Days 1, 8, 15, and 22 with no less than 4 days between dosing days. Dose calculations were based on body surface area using the subject's height (from Screening) and actual weight for each course.

Marqibo® (vincristine sulfate liposomes injection)

Susan O'Brien, MD

This was a Phase 2, international, multicenter, open-label, single-arm trial evaluating Marqibo (VSLI) in adult subjects with: 1) Ph- ALL or lymphoblastic lymphoma in second or greater relapse; or 2) Ph- ALL or lymphoblastic lymphoma who failed 2 or greater treatment lines of anti-leukemia chemotherapy. The original enrollment target for this study was approximately 56 subjects. Per a protocol amendment, enrollment was increased from 56 to 65.

The primary objective of this study was to evaluate:

- The efficacy of the study treatment as determined by the rate of CR plus CR with incomplete blood count recovery (CRi) in adult subjects with Philadelphia chromosome-negative (Ph-) ALL in second relapse or adult subjects with (Ph-) ALL who failed 2 treatment lines of anti-leukemia chemotherapy. Subjects must have achieved a CR to at least 1 prior anti-leukemia therapy as defined by a leukemia-free interval of ≥ 90 days.

The secondary objectives of this study were to evaluate:

* Duration of CR plus CRi
* Overall survival
* Safety and tolerability

Safety and Efficacy of Marqibo in Relapsed Acute Lymphoblastic Leukemia

A Phase 2 Study to Evaluate the Safety and Efficacy of Weekly Doses of Marqibo® (Vincristine Sulfate Liposomes Injection) in Adult Patients With Philadelphia Chromosome-negative Acute Lymphoblastic Leukemia (ALL) in Second Relapse or Adult Patients With Philadelphia Chromosome-negative ALL Who Failed Two Treatment Lines of Anti-leukemia Chemotherapy

CR is defined as no evidence of ALL: ANC\>or=1x10\^9/L or platelet count\>100x10\^9/L, absence of leukemia blast cells in blood and marrow (\<5% blasts), resolution of all sites of extramedullary disease (EMD). CR with incomplete blood count recovery (CRi): As per CR but platelet count\< 100x10\^9/L or ANC\< 1x10\^9/L. Partial remission(PR):CR with\>5-25% abnormal cells in the marrow or 50% decrease in bone marrow blasts. Reduction in EMD by at least 50%. Hematologic Improvement. Bone marrow blast(BMB) response: BMB\<5% in the absence of HI. Stable disease(SD):No significant hematological and extramedullary change from baseline.

Number of subjects who achieved Complete Remission (CR)as assessed by the IRRC. CR is defined as no evidence of ALL. ANC\>=1X10\^9/L or Platelet count\>=100x10\^9/L, absence of blasts in blood and morrow (\<5%), resolution of all sites of extramedullary disease (EMD). CR with incomplete blood count recovery(CRi)is defined as per CR but platelet count \<100x10\^9/L or ANC\<1x10\^9/L.

Duration of response for those subjects who achieved CR or CRi

Time, in days, from informed consent date until the date of death or date of last contact

Parexel

Spectrum Pharmaceuticals, Inc

Eligible subjects received study drug at 2.25 mg/m2 intravenously via peripheral or central venous access over 60 minutes (± 10 minutes).

Marqibo

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Canada

Israel

Germany

Region of Enrollment

Chief Medical Officer

Subjects who had CR plus CRi by the PI and the IRRC assessments using the International Working Group Criteria. The Intent-to-Treat Analysis, n=65, minimum 1 dose. The IRRC, n=53, 1 dose, assess response as determined by the IRRC. Analyses, a Simon's 2-stage minimax design where the type I error alpha was set at 0.10 and the power was 80%.

Complete Remission Plus Complete Remission Without Full Platelet Recovery (CR + CRi)

Duration of response derived using the IRRC determined response dates for subjects who achieved CR or CRi (n=8). The K-M product limit method was used to estimate the median event time.

Eligible subjects received Marqibo at 2.25mg\^m2 intravenously via peripheral or central venous access over 60 minutes (+- 10 minutes)every 7 days (+/- 3 days)

Based on the first date of CR or CRi to the date of the last available histologic assessment of the same response (n=8)

Duration of CR + CRi

The population analyzed included all subjects who received at least one dose of Marqibo. Subjects who did not die had their survival times censored on the date of last contact. The K-M method was used to estimate the distribution of overall survival.

Eligible subjects received study drug at 2.25 mg/m2 intravenously via peripheral or central venous access over 60 minutes (± 10 minutes)every 7 days (+/- 3 days)

Based on the first date of CR or CRi to date of documented relapse, death, or subsequent chemotherapies including hematopoietic stem cell transplant (HSCT)(n=10)

Overall Survival

Proportion if subjects who achieved CR+CRi as determined by the IRRC using the International Working Group (IWG)Criteria. The IRRC Evaluable analysis set(n=53) included subjects who received at least 1 dose of study drug and reviewable data.

Eligible subjects received Marqibo at 2.25mg\^m2 intravenously via peripheral or central venous access over 60 minutes (+/-10 minutes) every 7 days (+/-3days)

The IRRC evaluable population included all subjects who received at least 1 dose of study drug and who has reviewable data to assess and determine response or lack of response as determined by the IRRC.

Clinical Response Assessment Per Independent Response Review Committee (IRRC) Evaluation

Overall Study

Leukemia, Lymphocytic, Chronic, B-Cell

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Antirheumatic Agents

Reproductive Control Agents

Anti-Infective Agents

Vitamins

Rituximab

Gossypol acetic acid

Gossypol

Acetic Acid

Retinol acetate

Contraceptive Agents

Contraceptive Agents, Female

Spermatocidal Agents

Contraceptive Agents, Male

80 mg of AT-101 once daily for three days every other week, 375 mg/m2 of rituximab weekly for up to 12 weeks

AT-101

Thomas Kipps, MD, PhD

This is an open-label Phase 2 study to evaluate the safety and efficay of AT-101 in combination with rituximab in patients with relapsed or refractory chronic lymphocytic leukemia.

Phase 2 Safety and Efficacy Study of AT-101 in Combination With Rituximab in Patients With Chronic Lymphocytic Leukemia

A Phase 2, Open Label Study of AT-101 in Combination With Rituximab in Patients With Relapse or Refractory Chronic Lymphocytic Leukemia

Ascenta Therapeutics

Brian Wood, Associate Director, Clinical Development

Lymphoma, Mantle-Cell

Lymphoma, Follicular

Lymphoma, Large B-Cell, Diffuse

Lymphoma, Non-Hodgkin

Lymphoma, B-Cell

Mantle Cell Lymphoma

Follicular Lymphoma

Diffuse Large B-Cell Lymphoma

B-cell Lymphoma

Lance Leopold, MD

This is an open-label, multicenter, phase II study to evaluate the safety and efficacy of single-agent AT-101 in patients with relapsed or refractory B-cell malignancies.

This is an open-label, multicenter, phase II study to evaluate the safety and efficacy of single-agent AT-101 in patients with relapsed or refractory B-cell malignancies. For the purpose of this study, B-cell malignancies can include one of the following disease sub-types: follicular lymphoma (FL), diffuse large b-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), small lymphocytic lymphoma (SLL)/chronic lymphocytic leukemia. Patients will be enrolled according to disease subtype into one of four groups in two stages. The first stage of each group will enrolled 13 patients. If patients within any group experience disease response, an additional 14 patients will be enrolled into that group.

Phase II Safety and Efficacy Study of Single-agent AT-101 in Patients With Relapsed or Refractory B-cell Malignancies

A Phase II, Open Label, Multicenter Study of Single-Agent AT-101 in Patients With Relapsed or Refractory B-Cell Malignancies (Follicular Lymphoma, Mantle Cell Lymphoma, Diffuse Large Cell Lymphoma, or Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia)

Lance Leopold

Leukemia, Myeloid

Hematologic Neoplasms

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Bone Marrow Diseases

Leukocyte Disorders

Myeloproliferative Disorders

Translocation, Genetic

Chromosome Aberrations

Myeloid Leukemia

Chronic Myeloid Leukemia

Chronic Myeloproliferative Disorders

Amino Acids

Nilotinib

Imatinib Mesylate

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Nilotinib was supplied as 50 mg, 150 mg and 200 mg hard gelatin capsules and administered orally at 300 mg BID (twice a day) or 400 mg BID (twice a day)depending on the randomized dose.

nilotinib

Imatinib was supplied as 100 mg and 400 mg tablets and administered orally at 400 mg QD (once a day).

imatinib

Novartis Pharmaceuticals

In this study, the efficacy and safety of two nilotinib doses, 300 mg twice daily and 400 mg twice daily, were compared with imatinib 400 mg once daily in newly diagnosed patients with Philadelphia chromosome-positive (Ph+) Chronic Myelogenous Leukemia in the chronic phase (CML-CP).

An extension protocol was included in this study design to allow patients who did not show sufficient response to their assigned treatments the opportunity to receive imatinib 400 mg BID (option available until protocol amendment 7) or nilotinib 400 mg BID, using an abbreviated safety and efficacy assessment schedule.

Primary objectives of this study:

* Compared the efficacy (major molecular response (MMR) rate at 12 months) of nilotinib at 400 mg bid with that of imatinib 400 mg qd in newly diagnosed, previously untreated Ph+ CML-CP patients.
* Compared the efficacy (MMR rate at 12 months) of nilotinib at 300 mg bid with that of imatinib 400 mg qd in newly diagnosed, previously untreated Ph+ CML-CP patients.

The Primary objectives of Extension Phase of the study:

- Characterized the safety and tolerability profile of nilotinib 400 mg BID after failure of imatinib or insufficiently responded to nilotinib 300 mg BID therapy and the safety and tolerability profile of imatinib therapy after failure of nilotinib therapy.

The study was designed to determine whether the treatment of newly diagnosed, previously untreated Ph+ CML-CP patients with either nilotinib 300 mg bid or 400 mg bid demonstrated improved efficacy compared to imatinib 400 mg qd. The primary efficacy endpoint was the rate of MMR defined as the proportion of patients who achieved ≥ 3 log reduction in BCR-ABL transcripts compared to either the standardized Baseline established in the IRIS trial (International Randomized Interferon versus STI571) (Cortes et al 2005) or to the BCR-ABL ratio ≤ 0.1% by International Scale, as detected by real-time quantitative polymerase chain reaction (RQ-PCR) at 12 months.

The key secondary endpoint was to compare the rate of durable MMR between nilotinib 300 mg bid with that of imatinib, and of nilotinib 400 mg bid with that of imatinib at 24 months. This report presents the final results of efficacy and safety at the LPLV (21-Aug-2019).

The main data analysis was done at the time when all patients completed 12 cycles of treatment (or discontinued earlier). There were two primary comparisons at this time point: the MMR rate of nilotinib 400 mg versus the MMR rate of imatinib 400 mg, and the MMR rate of the nilotinib 300 mg versus the MMR rate of the imatinib 400 mg. Comparisons were done sequentially, i.e. the MMR rate of nilotinib 400 mg versus the MMR rate of imatinib 400 mg was to be compared first; if it was significant at 5% level, the MMR rate of the nilotinib 300 mg versus the MMR rate of the imatinib 400 mg was to be compared. The study had a 90% power to detect a 15% difference between the nilotinib 400 mg arm versus imatinib 400 mg arm assuming that the MMR rate of imatinib is 40% and the MMR rate of nilotinib is 55%. The study also had a 90% power to detect a 15% difference between the nilotinib 300 mg and the imatinib 400 mg arms, if the comparison between the nilotinib 400 mg and the imatinib 400 mg was significant.

The second main data analysis was done at the time when all patients completed 24 cycles of treatment (or discontinued earlier). There were two key comparisons at this time point: the rate of durable MMR at 24 months of the nilotinib 400 mg versus the imatinib 400 mg, and the rate of durable MMR at 24 months of the nilotinib 300 mg versus the imatinib 400 mg.

In order to control the overall type I error rate at or below 5%, only when the corresponding comparison on the primary efficacy endpoint(s) was (were) significant, the key secondary comparison(s) of the respective nilotinib doses (400 mg bid and/or 300 mg bid) versus imatinib 400 mg qd were tested at two-sided 5% significance level.

Patients participating after demonstrating suboptimal response/treatment failure to their assigned study treatment in the core study were offered the option to continue in the extension study and to receive imatinib 400 mg bid (option available only until protocol amendment 7) or nilotinib therapy at a dose of 400 mg bid.

A Study of Imatinib Versus Nilotinib in Adult Patients With Newly Diagnosed Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)

A Phase III Multi-center, Open-label, Randomized Study of Imatinib Versus Nilotinib 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

MMR is defined as the percentage of participants in MMR (reduction of ≥ 3 logs in BCR-ABL transcripts compared to the standardized baseline established in IRIS, or ≤ 0.1% BCR-ABL/ABL % by international scale and measured by real-time quantitative polymerase chain reaction (RQ-PCR)) at 12 months.

Durable MMR at 24 months is defined as having MMR both at 12 months and at 24 months, and with no documented loss of MMR between these 12 month and 24 month time points.

CCyR is defined as 0% Ph+ metaphases based on at least 20 metaphases from bone marrow cytogenetics. Patients with no CCyR as the best response by any specific time point, all missing cytogenetic evaluations by that time point or Ph- at baseline are combined as "Nocomplete cytogenetic response".

MMR is defined as the percentage of participants in MMR (reduction of ≥ 3 logs in BCR-ABL transcripts compared to the standardized baseline established in IRIS, or ≤ 0.1% BCR-ABL/ABL % by international scale and measured by real-time quantitative polymerase chain reaction (RQ-PCR)) at 12 months based on 12-month cut-off interim data.

MMR is defined as the percentage of participants in MMR (reduction of ≥ 3 logs in BCR-ABL transcripts compared to the standardized baseline established in IRIS, or ≤ 0.1% BCR-ABL/ABL % by international scale and measured by real-time quantitative polymerase chain reaction (RQ-PCR)) at 6 months and beyond up to 120 months based on final data.

Molecular response of \<=0.01% is defined as BCR-ABL ratio (%) on IS \<= 0.01% (corresponds to \>=4 log reduction of BCR-ABL transcripts from standardized baseline value)

This is the molecular response of \<=0.0032% is defined as BCR-ABL ratio (%) on IS \<= 0.0032% (corresponds to \>=4.5 log reduction of BCR-ABL transcripts from standardized baseline value)

Time to MMR is defined as time from date of randomization to the date of the first documented MMR in nilotinib treatment arms, compared to imatinib in adult patients with Ph+ CML in CP.

Duration of MMR for patients with MMR is defined as the time between date of MMR and the earliest of the following: loss of MMR, CML-related death or progression to AP/BC during study treatment The time will be censored at last molecular assessment (PCR) date for patients for whom none of the above events is reported.

Time to BCR-ABL ratio of ≤ 0.01% and ≤ 0.0032% is defined as: date of first BCR-ABL ratio of ≤ 0.01% and ≤ 0.0032% - date of randomization +1.

It is defined as the time from the date of first documented BCR-ABL ratio of ≤ 0.01% and ≤ 0.0032% to the earliest of the following: Loss of BCR-ABL ratio of ≤ 0.01% and ≤ 0.0032%, respectively, CML-related death or progression to AP/BC during study treatment. The time will be censored at last molecular assessment (PCR) date for patients for whom none of the above events is reported.

Rate of hematologic response is defined as the percentage of participants in complete hematologic response (defined as the following present for at least 4 weeks: WBC count \<10 x 109/L, Platelet count \<450 x 109/L, Basophils \<5%, No blasts and promyelocytes in peripheral blood, Myelocytes + metamyelocytes \< 5% in peripheral blood, No evidence of extramedullary disease, including spleen and liver).

Time to CCyR is defined as the time from the date of randomization to the date of first documented CCyR

Duration of CCyR is defined as the time from date of first documented CCyR to the earliest date of loss of CCyR.

Progression-free survival is defined as the time from the date of randomization to the date of event defined as the first documented disease progression to AP/BC or the date of death from any cause occurring in the core or extension study, or during the follow-up period after discontinuation of core or extension study

Event-free survival is defined as the time from the date of randomization to the date of first occurrence of any of the following: death due to any cause (if death is the primary reason for discontinuation), progression to AP or BC, loss of PCyR, loss of CCyR, loss of CHR

OS is defined as the time from the date of randomization to the date death. Up to 10 calendar years of follow up from the date when the last patient randomized received the first dose of study drug in all active treatment arms of adult patients with Ph+ CML CP.

Actual dose intensity is defined as total dose over time on treatment

Time to progression to AP/BC is defined as the time from the date of randomization to the date of event defined as the first documented disease progression to AP/BC or the date of CML related death.

Cmax is defined as the maximum serum concentration after dose

Cmin is defined as the minimum serum concentration after dose

Tmax is defined as the sampling time when maximum measured serum concentration occurs

AUC0-last is defined as area under concentration-time curve from time zero to the last measurable sample, calculated by log-linear trapezoidal method

Rate of CCyR is defined as the percentage of participants in complete cytogenetic response (CCyR). CcyR is defined as 0% of Ph+ metaphases in the bone marrow.

Rate of MMR is defined as the percentage pf participants in MMR (reduction of ≥ 3 logs in BCR-ABL transcripts compared to the standardized baseline established in IRIS, or ≤ 0.1% BCR-ABL/ABL % by international scale and measured by real-time quantitative polymerase chain reaction (RQ-PCR))

Molecular response of \<=0.0032% is defined as BCR-ABL ratio (%) on IS \<= 0.0032% (corresponds to \>=4.5 log reduction of BCR-ABL transcripts from standardized baseline value)

This is the percentage of patients with any emergent mutation on extension treatment. The mutation comprised of T315T, less sensitive to nilotinib, unknown and sensitive to nilotinib.

Adverse Event (AE): Any sign or symptom that occurs during the study treatment plus 28 days post treatment.

Patients randomized to this arm were to receive 400 mg imatinib once a day (QD). If the patient required a dose escalation from 400 mg/day, the patient was to receive 400 mg imatinib twice daily orally. Imatinib was taken with food and a large glass of water. All patients were to avoid grapefruit, star fruit, pomegranate and Seville oranges or juices and products containing these fruits during the study. In cases of vomiting doses were not to be repeated

Imatinib 400 mg QD

Patients who were randomized to this arm were to receive nilotinib 300 mg twice a day (BID) by mouth each morning and evening approximately 12 hours apart. If the morning or evening dose was delayed for more than 4 hours, the patient was to skip this dose and resume dosing with the next dose as per the original schedule in order to prevent overdosing. No imatinib washout period was necessary prior to administration of nilotinib. Nilotinib was not to be taken with food. No food was to be consumed for at least 2 hours before the dose was taken and no additional oral intake other than water was to be consumed for at least one hour after the dose was taken. Patients were instructed to swallow capsules whole with a full 8 ounce glass of water, and not to chew them. All patients were to avoid grapefruit, star fruit, pomegranate and Seville oranges or juices and products containing these fruits. Vomited doses were not to be repeated.

Nilotinib 300 mg BID

Patients who were randomized to this arm were to receive nilotinib 400 mg twice a day (BID) by mouth each morning and evening approximately 12 hours apart. If the morning or evening dose was delayed for more than 4 hours, the patient was to skip this dose and resume dosing with the next dose as per the original schedule in order to prevent overdosing. No imatinib washout period was necessary prior to administration of nilotinib. Nilotinib was not to be taken with food. No food was to be consumed for at least 2 hours before the dose was taken and no additional oral intake other than water was to be consumed for at least one hour after the dose was taken. Patients were instructed to swallow capsules whole with a full 8 ounce glass of water, and not to chew them. All patients were to avoid grapefruit, star fruit, pomegranate and Seville oranges or juices and products containing these fruits. Vomited doses were not to be repeated.

Nilotinib 400 mg BID

All patients randomized in the study to all 3 arms and received at least one dose of study drug.

All Patients

Nilotinb 300 mg BID

Total

<35 years

>= 35 - <45 years

>=45 - <55 years

>=55 - < 65 years

>=65 years

Age, Customized

Caucasian

Black

Asian

Native American

Other

Missing patient that cannot be identified

Race/Ethnicity, Customized

Full analysis Set (FAS): Contained 846 randomized patients. Patients were analyzed according to the treatment they were randomized to, regardless of actual treatment received.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Safety and Efficacy of Marqibo in Relapsed Acute Lymphoblastic Leukemia	NCT00495079	Acute Lymphobla...	Marqibo® (vincr...	18 Years -	Spectrum Pharmaceuticals, Inc
Safety and Efficacy of Marqibo in Relapsed Acute Lymphoblastic Leukemia	NCT00495079	Acute Lymphobla...	Marqibo® (vincr...	18 Years -	Spectrum Pharmaceuticals, Inc
Phase 2 Safety and Efficacy Study of AT-101 in Combination With Rituximab in Patients With Chronic Lymphocytic Leukemia	NCT00286780	Chronic Lymphoc...	AT-101	18 Years -	Ascenta Therapeutics
Phase II Safety and Efficacy Study of Single-agent AT-101 in Patients With Relapsed or Refractory B-cell Malignancies	NCT00275431	Follicular Lymp... Diffuse Large C... Mantle Cell Lym... Small Lymphocyt... Chronic Lymphoc...	AT-101	18 Years -	Ascenta Therapeutics
A Study of Imatinib Versus Nilotinib in Adult Patients With Newly Diagnosed Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)	NCT00471497	Myelogenous Leu...	nilotinib imatinib	18 Years -	Novartis
Phase 2 Safety and Efficacy Study of AT-101 in Combination With Rituximab in Patients With Chronic Lymphocytic Leukemia	NCT00286780	Chronic Lymphoc...	AT-101	18 Years -	Ascenta Therapeutics

Spots Global Cancer Trial Database for lukemia

Every month we try and update this database with for lukemia 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 lukemia

Every month we try and update this database with for lukemia 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 lukemia 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.