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

VSI dosed at 1.4 mg/m\^2 with a 2 mg dose cap as an intravenous (IV) infusion over 10 minutes.

Marqibo dosed at 2.25 mg/m\^2 (without any dose cap) as an IV infusion over 60 minutes.

2.25 mg/m\^2 (without any dose cap) as an IV infusion over 60 minutes.

Vincristine Sulfate Liposomes Injection (VSLI)

1.4 mg/m\^2 with a 2 mg dose cap as an IV infusion over 10 minutes.

Vincristine Sulfate Injection (VSI)

Susan M O'Brien, MD

A phase 3 study in the treatment of subjects \>or= 60 years old with newly diagnosed acute lymphoblastic leukemia (ALL).

A phase 3, multicenter, randomized study to evaluate the substitution of Marqibo® (Vincristine Sulfate Liposomes Injection, VSLI) for standard Vincristine Sulfate Injection (VSI) in the induction, intensification, and maintenance phases of combination chemotherapy in the treatment of subjects \>or= 60 years old with newly diagnosed acute lymphoblastic leukemia (ALL).

A Phase 3 Study to Evaluate Marqibo® in the Treatment of Subjects ≥ 60 Years Old With Newly Diagnosed ALL

Phase 3 Study of Study to Evaluate Marqibo® in the Combination Chemotherapy in the Treatment of Subjects >or=60 Years Old With Newly Diagnosed Acute Lymphoblastic Leukemia (ALL)

Overall survival was defined as the time from the date of study randomization until death from any cause. Observations censored at the date of the last follow-up for subjects not known to have died.

VSI dosed at 1.4 mg/m\^2 with a 2 mg dose cap as an IV infusion over 10 minutes.

Total

Race (NIH/OMB)

Gajanan Bhat, PhD

Data for this outcome measure was not collected due to early termination of study.

Nervous System Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Diseases and Abnormalities at or Before Birth

Hematologic Neoplasms

Sarcoma

Brain Neoplasms

Wilms Tumor

Neuroblastoma

Neoplasms, Connective and Soft Tissue

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Syndrome

Neoplastic Syndromes, Hereditary

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Genetic Diseases, Inborn

Soft Tissue Sarcoma

Wilms' Tumor

Neuroepithelioma

Marqibo® (Vincristine sulfate liposomal) will be administered intravenously over 60 minutes (±10 minutes) every 7 days (±3 days) (Days 1, 8, 15, 22) for four doses (1 cycle). Cycles may be repeated every 28 days for a maximum of 6 cycles; additional cycles may be offered with evidence of acceptable toxicity and clinical benefit.

* The trial follows a rolling phase I design with 2 to 6 subjects per dose level and standard definitions of MTD and DLT. At the MTD, a total of 6 additional subjects with relapsed or refractory ALL will be evaluated.
* Detailed pharmacokinetic studies will be performed during the first treatment cycle

Marqibo® intravenously (IV) over 60 minutes (+ 10 minutes) every 7 days (+ 3 days) for 4 consecutive weeks (day 1, 8, 15, 22) for a 28-day treatment cycle

Allen Wayne

Background:

* Marqibo(Registered Trademark) is a new anticancer drug. It combines Vincristine sulfate, which is a widely used anticancer drug, and packages it into a tiny fat bubble known as a liposome. The goal of this is to improve the drug's ability to destroy cancer cells and help reduce the potential side effects of treatment.
* Vincristine sulfate was originally developed from chemicals found in the periwinkle plant and acts against multiple types of malignant cancer. It is approved for multiple cancer types including solid tumors and blood cancers.
* Research has shown that Marqibo(Registered Trademark) is able to slow or stop the growth of cancer cells in some adults, both alone and in combination with other chemotherapy drugs, but more research is needed to determine its use in children.
* There has been one previous small study of Marqibo(Registered Trademark) in children. Although some anti-cancer activity was seen, side effects and optimal dosing were not fully determined.
* As is seen with standard Vincristine suflate, the most common side effect of Marqibo(Registered Trademark) involves the nervous system. It can cause numbness and tingling in the hands and feet. Symptoms commonly improve when the drug is discontinued or the dose is lowered.

Objectives:

- To determine the safety and efficacy of Marqibo as a treatment for children who have been diagnosed with certain types of malignant cancer that has not responded to standard treatment.

Eligibility:

* Children and adolescents between 2 and 21 years of age who have been diagnosed with certain types of malignant cancer that has not responded to standard treatment.
* These cancer types include solids tumors, primary brain tumors, leukemias, and lymphomas.

BACKGROUND

* Vincristine sulfate is a widely used antineoplastic agent of the alkaloid class of drugs derived from the periwinkle plant (Vinca rosea Linn.). It has activity against a wide number of malignancies. It is a cell-cycle-specific agent that arrests cell growth in the M-phase (metaphase) by binding specifically with tubulin and disrupting cell division. Its dose limiting toxicity (DLT) is virtually always neurological.
* Investigations over the past two decades have demonstrated that liposomal drug carriers are capable of increasing the therapeutic index of anticancer drugs by altering the drug s pharmacological behavior.
* Marqibo(Registered Trademark) is vincristine encapsulated in sphingomyelin/cholesterol (SM/CHOL) liposomes, developed to increase the activity of vincristine. It has been shown to have activity in Phase 2 studies in adults. Previous investigation of Marqibo(Registered Trademark) in children is limited. A small phase 2 study was conducted with dosing of 2.0mg/m2 every 14 days. The agent appeared to be well tolerated and some activity was seen, although data were quite limited.

OBJECTIVES

* To define the maximum tolerated dose (MTD), toxicity profile, dose-limiting toxicities, and pharmacokinetics in children and adolescents with solid tumors or hematologic malignancies receiving weekly intravenous doses of Marqibo(Registered Trademark).
* To define the tolerability and potential activity of Marqibo(Registered Trademark) in children and adolescents with relapsed or refractory acute lymphoblastic leukemia (ALL) at the pediatric MTD.

ELIGIBILITY

- Children and adolescents (greater than or equal to 2 years and \< 21 years of age) with histologically confirmed relapsed or refractory malignant disease that is measurable or evaluable.

DESIGN

* Marqibo(Registered Trademark) will be administered intravenously over 60 minutes (+ or -10 minutes) every 7 days (+ or - 3 days) (Days 1, 8, 15, 22) for four doses (1 cycle). Cycles may be repeated every 28 days for a maximum of 6 cycles; additional cycles may be offered with evidence of acceptable toxicity and clinical benefit.
* The trial follows a standard phase I design with 3 to 6 subjects per dose level and standard definitions of MTD and DLT. At the MTD, a total of 6 additional subjects with relapsed or refractory ALL will be evaluated.
* Detailed pharmacokinetic studies will be performed during the first treatment cycle.

Phase 1 Trial to Evaluate the Safety, Activity and Pharmacokinetics of Marqibo® (Vincristine Sulphate Liposomes Injection) in Children and Adolescents with Refractory Cancer

To Evaluate the Safety, Activity and Pharmacokinetics of Marqibo in Children and Adolescents With Refractory Cancer

Phase I Trial to Evaluate the Safety, Activity and Pharmacokinetics of Marqibo(Registered Trademark) (Vincristine Sulfate Liposomes Injection) in Children and Adolescents With Refractory Cancer

Toxicity was graded according to the version 4.0 of the NCI Common Toxicity Criteria (CTCAE v4.0).

The MTD was defined as the dose level immediately below the dose level at which ≥2 subjects in a cohort of 2 to 6 subjects experienced a DLT.

DLT was graded according to the version 4.0 of the NCI Common Toxicity Criteria (CTCAE v4.0). Adverse events (AEs) that were considered disease-related (not suspected of relationship to Marqibo) were not considered dose-limiting toxicities. Only those AEs deemed suspected of a relationship to Marqibo were used in the definition of DLT.

PK samples were collected at cycle 1 before start of first infusion, 5 minutes post-infusion and at 1, 3, 6, 10, 24, 48, 72, 96, 120 and 144 hours (pre-dose #2 trough level). Area under the concentration time curve (AUC) to last measured time point after dose one was calculated via linear trapezoidal method and extrapolated to infinity (AUC0-∞) by adding the last plasma concentration after dose one divided by the rate constant, derived from the slope of the natural log-transformed concentrations and times on the terminal elimination phase of the concentration-time curve.

National Cancer Institute (NCI)

Acrotech Biopharma Inc.

Acute Disease

Disease Attributes

Childhood Acute Lymphoblastic Leukemia

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Analgesics

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Dexamethasone

Mitoxantrone

Methotrexate

Dexamethasone acetate

Pegaspargase

Mercaptopurine

Asparaginase

* Marqibo®: given by intravenous (IV) infusion on days 1, 8, 15 and 22.
* Dexamethasone orally twice daily on days 1-5 and 15-19.
* Mitoxantrone: given by intravenous (IV) infusion on days 1 and 2.
* PEG-asparaginase: given as an injection into the muscle on says 3 and 17.
* Methotrexate IT: given intrathecally (used to treat the brain and spinal cord and is given using a needle inserted into the spinal canal) on days 1 and 8.

* Marqibo®: given by intravenous (IV) infusion on days 1, 8, 15 and 22.
* Dexamethasone orally twice daily on days 1-5 and 15-19.
* PEG-asparaginase: given as an injection into the muscle on days 3 and 17.
* Methotrexate IT: given intrathecally (used to treat the brain and spinal cord and is given using a needle inserted into the spinal canal) on days 1 and 8.

* Marqibo®: given by intravenous (IV) infusion on day 1
* Dexamethasone orally twice daily on days 1-5
* Methotrexate: given orally on days 1 and 8
* Mercaptopurine: given orally daily on days 1-13

The focus of the study design and statistical analysis is to determine whether Marqibo® can be substituted for standard vincristine and successfully administered to patients with relapsed ALL in three different treatment cohorts: (A) treatment with the UK ALL R3 regimen; (B) treatment with UK ALL R3 regimen without mitoxantrone, and (C) treatment with ALL maintenance therapy. Secondary objectives include estimating rates of serious toxicities and therapy delays in each of these cohorts.

Ellynore Florendo

Lei-Lani Miller

Alan Wayne, MD

Van Thu Huynh, MD

Michelle Hermiston, MD

Lia Gore, MD

Reuven Schore, MD

Julio Barredo, MD

Gregory Hale, MD

Melinda Pauly, MD

Nobuko Hijiya, MD

Patrick Brown, MD

Nirali Shah, MD

Lewis Silverman, MD

Raymond J Hutchinson, MD

Yoav Messinger, MD

Maria Luisa Sulis, MD

Joel Kaplan, DO

Maureen O'Brien, MD

Robin Norris, MD, MS, MPH

Robyn Dennis, MD

Bill Chang, MD

Susan Rheingold, MD

Howard Katzenstein

Ted Laetsch, MD

Kenneth Heym, MD

Eric S Schafer, MD, MHS

Elizabeth Raetz, MD

Todd Cooper, MD

Mike Burke, MD

David Ziegler, MD

Luciano Dalla-Pozza, MD

Chris Fraser, MD

Francoise Mechinaud, MD

Kirk Schultz, MD

Jim Whitlock, MD

Henrique Bittencourt, MD

This is a pilot study utilizing Marqibo® (vincristine sulfate liposome injection) combined with dexamethasone, mitoxantrone and asparaginase (UK ALL R3) for relapsed acute lymphoblastic leukemia (ALL).

This study will utilize Marqibo® as a replacement for standard vincristine in combination with chemotherapy for children with relapsed ALL. The hypothesis is that the incorporation of Marqibo® with combination chemotherapy will be safe and feasible. In the context of this pilot study, overall outcomes and efficacy will be a secondary objective. It is hypothesized that data from this combination may show improved efficacy including, complete remission (CR), minimal residual disease (MRD) negativity, and progression free survival (PFS) rates and safety (i.e., neurotoxicity) in comparison to outcomes in historical regimens, including the UK ALL R3 with standard vincristine.

Vincristine Sulfate Liposome Injection (Marqibo®) in Combination With UK ALL R3 Induction Chemotherapy for Children, Adolescents, and Young Adults With Relapsed ALL

A Pilot Study of Vincristine Sulfate Liposome Injection (Marqibo®) in Combination With UK ALL R3 Induction Chemotherapy for Children, Adolescents, and Young Adults With Relapse of Acute Lymphoblastic Leukemia

The incidence of dose limiting toxicity (DLT) will be measured at different dose levels.

The rate of remission will be assessed after 1 courses of therapy. A bone marrow aspirate/biopsy and CBC will be conducted to assess response.

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
A Phase 3 Study to Evaluate Marqibo® in the Treatment of Subjects ≥ 60 Years Old With Newly Diagnosed ALL	NCT01439347	Acute Lymphobla...	Vincristine Sul... Vincristine Sul...	60 Years -	Spectrum Pharmaceuticals, Inc
To Evaluate the Safety, Activity and Pharmacokinetics of Marqibo in Children and Adolescents With Refractory Cancer	NCT01222780	Sarcoma Neuroblastoma Wilms Tumor Leukemia Lymphoma Brain Tumors	Marqibo	2 Years - 20 Years	Acrotech Biopharma Inc.
To Evaluate the Safety, Activity and Pharmacokinetics of Marqibo in Children and Adolescents With Refractory Cancer	NCT01222780	Sarcoma Neuroblastoma Wilms Tumor Leukemia Lymphoma Brain Tumors	Marqibo	2 Years - 20 Years	Acrotech Biopharma Inc.
Vincristine Sulfate Liposome Injection (Marqibo®) in Combination With UK ALL R3 Induction Chemotherapy for Children, Adolescents, and Young Adults With Relapsed ALL	NCT02879643	ALL, Childhood Lymphoblastic L... Lymphoblastic L...	Marqibo	1 Year - 21 Years	Therapeutic Advances in Childhood Leukemia Consortium
Vincristine Sulfate Liposome Injection (Marqibo®) in Combination With UK ALL R3 Induction Chemotherapy for Children, Adolescents, and Young Adults With Relapsed ALL	NCT02879643	ALL, Childhood Lymphoblastic L... Lymphoblastic L...	Marqibo	1 Year - 21 Years	Therapeutic Advances in Childhood Leukemia Consortium

Spots Global Cancer Trial Database for marqibo

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

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