Symptoms and General Pathology

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Rare Diseases

Recurrence

Breast Neoplasms

Breast Neoplasms, Male

Breast Diseases

Skin Diseases

Breast Cancer, Male

Antineoplastic Agents

All Drugs and Chemicals

Pixantrone

Enzyme Inhibitors

Patients receive pixantrone dimaleate IV over 1 hour on day 1. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Patients receive pixantrone dimaleate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

pixantrone dimaleate

Alvaro Moreno-Asptia, MD

RATIONALE: Drugs used in chemotherapy, such as pixantrone dimaleate, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving pixantrone dimaleate in different ways may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying how well pixantrone dimaleate works in treating patients with HER2-negative metastatic breast cancer.

OBJECTIVES:

Primary

* To assess the proportion of confirmed tumor responses at each dose level of pixantrone

Secondary

* To describe the distribution of progression-free survival (PFS) times of patients receiving pixantrone
* To assess the 6-month PFS rate in patients receiving each dose level of pixantrone
* To describe the overall survival distribution of patients receiving pixantrone
* To assess the adverse event profile of pixantrone in the treatment of patients with metastatic breast cancer.
* To evaluate the quality of life and patient-reported symptoms of patients receiving the study regimen

OUTLINE: This is a multicenter study. Patients are randomized according to prior doxorubicin treatment ( yes vs no). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive pixantrone dimaleate IV over 1 hour on day 1. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
* Arm II: Patients receive pixantrone dimaleate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Some patients undergo blood sample collection at baseline and periodically during study for circulating tumor cells analysis by CellSearch System and mRNA isolation assays.

Patients complete quality-of-life questionnaires using the Linear Analogue Self Assessment (LASA6) and the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) at baseline and periodically during study.

After completion of study therapy, patients are followed up every 3-6 months for up to 5 years.

Pixantrone Dimaleate in Treating Patients With HER2-Negative Metastatic Breast Cancer

Randomized Phase II Study of Two Doses of Pixantrone in Patients With Metastatic Breast Cancer

The proportion of confirmed responses will be estimated by the number of women who achieve a CR or PR on two consecutive evaluations at least 6-8 weeks apart depending on the dose level. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients at each dose level. Confidence intervals for the true success proportion at each dose level will be calculated according to the approach of Duffy and Santner. Response will be evaluated in this study using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1); Complete Response (CR): Disappearance of all non-nodal target lesions, each target lymph node must have reduction in short axis to \<1.0 cm. and normalization of tumor biomarkers. Partial Response (PR): At least a 30% decrease in the sum of the longest diameters of the non-nodal target lesions and the short axis of the target lymph nodes taking as reference the Baseline Sum of Diameters.

Time to disease progression is defined as the time from registration to the earliest date of documentation of disease progression. If a patient dies without a documentation of disease progression the patient will be considered to have had disease progression at the time of their death. If the patient is declared to be a major treatment violation, the patient will be censored on the date the treatment violation was declared to have occurred. In the case of a patient starting treatment and then never returning for any evaluations, the patient will be censored for progression one day post-registration. The distribution of time to progression will be estimated using the method of Kaplan-Meier at each dose level. Progression is defined using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1).

The 6-month progression free survival (6-mo PFS) rate is the proportion of efficacy-evaluable patients progression-free 6 months from registration. The 6-mo PFS rate is defined as the total number of efficacy-evaluable patients on study without documentation of disease progression 6 months from registration divided by the total number of efficacy-evaluable patients enrolled on study. Patients who died without documentation of progression will be considered to have progressed on the date of their death. The true 6-mo PFS rate will be estimated by the proportion of efficacy-evaluable patients on study without documentation of disease progression 6 months from registration at each dose level. Binomial confidence intervals for 6-mo PFS rate will be constructed for each dose level. Progression is defined using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1).

Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier at each dose level.

Duration of response is defined for all evaluable patients with measurable disease who have achieved a confirmed response as the date at which the patient's earliest best objective status is first noted to be either a CR or PR to the earliest date progression is documented at each dose level. If a patient dies subsequent to the confirmed response without a documentation of disease progression, the patient will be considered to have had disease progression at the time of their death. In the case of a patient failing to return for evaluations before a documentation of disease progression, the patient will be censored for progression on the date of last evaluation. The distribution of duration of response will be estimated using the method of Kaplan-Meier at each dose level.

For this secondary endpoint, toxicity is defined as a grade 3 or higher adverse events that is classified as either possibly, probably, or definitely related to study treatment. The assignment of attribution to study treatment and grade (or degree of severity) of the adverse event are classified using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The number of participants reporting a grade 3 or higher toxicity is reported. For a list of all reported adverse events, please refer to the Adverse Events Section below.

National Cancer Institute (NCI)

Alliance for Clinical Trials in Oncology

The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.

Patients receive 180 mg/m\^2 pixantrone dimaleate IV over 1 hour on day 1. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Arm I/Group A

Patients receive 85 mg/m\^2 pixantrone dimaleate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Arm II/Group B

Arm I/Group A (Pixantrone IV Day 1)

Arm II/Group B (Pixantrone IV Days 1, 8, and 15)

Total

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Alvaro Moreno-Asptia, M.D.

Proportion of Confirmed Tumor Responses (Complete or Partial Response)

Time to Disease Progression

6-month Progression-free Survival Rate

Overall Survival Time

Arm I/Group A: Patients receive 180 mg/m\^2 pixantrone dimaleate IV over 1 hour on day 1. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Arm II/Group B: Patients receive 85 mg/m\^2 pixantrone dimaleate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Arm I/Group A + Arm II/Group B

Duration of Response

Toxicity

Overall Study

Blood and Lymph Conditions

Immune System Diseases

Lymphoma

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphoma, Follicular

Lymphoma, B-Cell, Marginal Zone

Lymphoma, B-Cell

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

Lymphosarcoma

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Follicular Lymphoma

B-cell Lymphoma

Marginal Zone Lymphoma

Antirheumatic Agents

Fludarabine

Fludarabine phosphate

Rituximab

Antineoplastic Agents, Immunological

Immunologic Factors

Antimetabolites

Immunosuppressive Agents

Patients receive rituximab IV on day 1 and fludarabine phosphate IV on days 2-4. Treatment repeats every 28 days for up to 6 courses.

Patients receive rituximab and fludarabine phosphate as in arm I. Patients also receive pixantrone IV on day 2. Treatment repeats every 28 days for up to 6 courses.

rituximab

fludarabine phosphate

Igor Gorbatchevsky, MD

RATIONALE: Drugs used in chemotherapy, such as fludarabine and pixantrone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. It is not yet known whether giving fludarabine together with rituximab is more effective with or without pixantrone in treating indolent non-Hodgkin lymphoma.

PURPOSE: This randomized phase III trial is studying fludarabine and rituximab to compare how well they work with or without pixantrone in treating patients with relapsed or refractory indolent non-Hodgkin lymphoma.

OBJECTIVES:

Primary

* To compare the progression-free survival (PFS) of patients with relapsed or refractory indolent non-Hodgkin lymphoma treated with fludarabine phosphate and rituximab with vs without pixantrone.

Secondary

* To compare the overall objective response rate (complete response \[CR\], unconfirmed complete response \[CRu\], and partial response \[PR\]) in these patients.
* To compare the CR and CRu rate in these patients.
* To compare the duration of response and time to progression in these patients.
* To compare the overall survival and disease-specific survival of these patients.
* To compare the safety (including cardiac safety) and tolerability of these regimens in these patients.

OUTLINE: This is a multicenter study. Patients are stratified by Follicular Lymphoma International Prognostic Index (FLIPI) score (0 or 1 vs ≥ 2), number of prior treatments (1 or 2 vs \> 2), and prior anti-CD20 regimen (yes vs no). Patients are randomized to 1 of 2 treatment arms.

* Arm I (control): Patients receive rituximab IV on day 1 and fludarabine phosphate IV on days 2-4. Treatment repeats every 28 days for up to 6 courses\* in the absence of unacceptable toxicity or disease progression.
* Arm II: Patients receive rituximab and fludarabine phosphate as in arm I. Patients also receive pixantrone IV on day 2. Treatment repeats every 28 days for up to 6 courses\* in the absence of unacceptable toxicity or disease progression.

NOTE: \*Only patients achieving complete response, unconfirmed complete response, or partial response after 4 courses receive courses 5 and 6.

After completion of study therapy, patients are followed periodically for up to 5 years.

Fludarabine and Rituximab With or Without Pixantrone in Treating Patients With Relapsed or Refractory Indolent Non-Hodgkin Lymphoma

A Randomized Phase III Trial Comparing the Combination of Fludarabine, BBR 2778 (Pixantrone) and Rituximab (FP-R) With the Combination of Fludarabine and Rituximab (F-R) in the Treatment of Patients With Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma

CTI BioPharma

Behaviors and Mental Disorders

Infections

Lymphoma, Large B-Cell, Diffuse

Aggression

Burkitt Lymphoma

Lymphoma, Large-Cell, Anaplastic

Plasmablastic Lymphoma

Lymphoma, Large-Cell, Immunoblastic

Diffuse Large B-Cell Lymphoma

Anaplastic Large Cell Lymphoma

Lymphoma, Large-cell, Immunoblastic

Anti-Infective Agents

Anti-Inflammatory Agents

Antiemetics

Neuroprotective Agents

Gastrointestinal Agents

Cytarabine

Cisplatin

Prednisolone

Lenograstim

Methylprednisolone

Methylprednisolone Acetate

Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

Prednisolone phosphate

Antiviral Agents

Glucocorticoids

Hormones

Hormone Antagonists

Protective Agents

filgrastim

cisplatin

cytarabine

methylprednisolone

autologous bone marrow transplantation

peripheral blood stem cell transplantation

Julie M. Vose, MD

RATIONALE: Drugs used in chemotherapy, such as pixantrone, cytarabine, methylprednisolone, and cisplatin, work in different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy in treating patients who have relapsed aggressive non-Hodgkin's lymphoma.

OBJECTIVES:

* Determine the antitumor activity of pixantrone, cytarabine, methylprednisolone, and cisplatin in patients with aggressive non-Hodgkin's lymphoma in first relapse.
* Determine the safety and tolerability of this regimen in these patients.
* Determine the validity and safety of this regimen as a mobilization regimen before high-dose chemotherapy with stem cell support in these patients.

OUTLINE: This is an open-label, multicenter study.

* Salvage therapy: Patients receive pixantrone IV over 1 hour on day 1; cisplatin IV over 30 minutes on days 1-4; methylprednisolone IV over 15-30 minutes on days 1-5; and cytarabine IV over 2 hours on day 5. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.

After 2 courses of salvage therapy, patients are re-evaluated and treated as follows:

* Complete response (CR) or partial response (PR): Patients with a CR or PR who are suitable candidates for autologous stem cell transplantation (ASCT) proceed to mobilization therapy, high-dose chemotherapy, and ASCT. Patients with a CR or PR who are unsuitable candidates for ASCT continue to receive salvage therapy for up to 6 courses in the absence of disease progression or unacceptable toxicity.
* Stable disease: Patients with stable disease continue to receive salvage therapy for up to 6 courses. Patients who have a CR or PR after 3-4 courses of salvage therapy and who are suitable candidates for ASCT proceed to mobilization therapy, high-dose chemotherapy, and ASCT off study at the investigator's discretion.

  * Mobilization therapy (optional regimen; regimen used for mobilization is at the investigator's discretion): Patients receive rituximab\* IV on days 1 and 7; pixantrone IV over 1 hour on day 2; cisplatin IV over 30 minutes on days 2-5; cytarabine IV over 2 hours on day 6; and methylprednisolone IV over 15-30 minutes on days 2-6. Patients also receive filgrastim (G-CSF) subcutaneously once daily beginning on day 7 and continuing until blood counts recover. Patients receive 1 or more courses of mobilization therapy during which stem cells are harvested. Patients then proceed to high-dose chemotherapy and subsequent re-infusion of harvested stem cells.

NOTE: \*If this mobilization regimen is used, patients with T-cell lymphoma do not receive rituximab

* High-dose chemotherapy and ASCT: Patients receive high-dose chemotherapy and ASCT per institutional standard practice.

Patients are followed every 3 months for 2 years.

PROJECTED ACCRUAL: A total of 75 patients will be accrued for this study.

Pixantrone, Cytarabine, Methylprednisolone, and Cisplatin in Treating Patients With Aggressive Non-Hodgkin's Lymphoma in First Relapse

A Phase II Trial of BBR 2778 in Combination With Cytarabine, Methylprednisolone and Cisplatin (BSHAP) as Salvage in Patients With Relapsed Aggressive Non-Hodgkin's Lymphoma

Theradex

Lymphoma, T-Cell

Lymphoma, T-Cell, Cutaneous

Cutaneous T-cell Lymphoma

Antineoplastic Agents, Hormonal

Luis Fayad, MD

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.

PURPOSE: Phase I trial to study the effect of combination chemotherapy on the body when treating patients who have relapsed or refractory aggressive non-Hodgkin's lymphoma.

OBJECTIVES:

* Determine the maximum tolerated dose and recommended dose of pixantrone when administered with cytarabine, methylprednisolone, and cisplatin in patients with relapsed or refractory aggressive non-Hodgkin's lymphoma.
* Determine the dose-limiting toxic effects of this regimen in these patients.
* Determine the relationship between toxicity and systemic exposure to this regimen in these patients.
* Determine the safety of this regimen in these patients.
* Assess the pharmacokinetics of this regimen in these patients.
* Determine, preliminarily, the efficacy of this regimen in these patients.

OUTLINE: This is an open-label, non-randomized, multicenter, dose-escalation study of pixantrone.

Patients receive pixantrone IV over 1 hour on day 1, methylprednisolone IV over 15 minutes on days 1-5, cisplatin IV over 30 minutes on days 1-4, and cytarabine IV over 2 hours on day 5. Treatment repeats every 21 days for at least 8 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of pixantrone until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 2 of 6 patients experience dose-limiting toxicity. Additional patients are treated at the recommended dose, which is defined as the dose preceding the MTD.

Patients are followed every 3 months.

PROJECTED ACCRUAL: Approximately 3-30 patients will be accrued for this study.

Combination Chemotherapy in Treating Patients With Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma

A Phase I Trial of BBR 2778 in Combination With Cytarabine, Methylprednisolone and Cisplatin in the Treatment of Patients With Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pixantrone Dimaleate in Treating Patients With HER2-Negative Metastatic Breast Cancer	NCT01086605	Breast Cancer	pixantrone dima...	18 Years -	Alliance for Clinical Trials in Oncology
Fludarabine and Rituximab With or Without Pixantrone in Treating Patients With Relapsed or Refractory Indolent Non-Hodgkin Lymphoma	NCT00551239	Leukemia Lymphoma	rituximab fludarabine pho... pixantrone dima...	18 Years - 120 Years	CTI BioPharma
Pixantrone, Cytarabine, Methylprednisolone, and Cisplatin in Treating Patients With Aggressive Non-Hodgkin's Lymphoma in First Relapse	NCT00069966	Lymphoma	filgrastim rituximab cisplatin cytarabine methylprednisol... pixantrone dima... autologous bone... peripheral bloo...	18 Years -	National Cancer Institute (NCI)
Fludarabine and Rituximab With or Without Pixantrone in Treating Patients With Relapsed or Refractory Indolent Non-Hodgkin Lymphoma	NCT00551239	Leukemia Lymphoma	rituximab fludarabine pho... pixantrone dima...	18 Years - 120 Years	CTI BioPharma
Fludarabine and Rituximab With or Without Pixantrone in Treating Patients With Relapsed or Refractory Indolent Non-Hodgkin Lymphoma	NCT00551239	Leukemia Lymphoma	rituximab fludarabine pho... pixantrone dima...	18 Years - 120 Years	CTI BioPharma
Pixantrone Dimaleate in Treating Patients With HER2-Negative Metastatic Breast Cancer	NCT01086605	Breast Cancer	pixantrone dima...	18 Years -	Alliance for Clinical Trials in Oncology
Combination Chemotherapy in Treating Patients With Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma	NCT00053105	Lymphoma	cisplatin cytarabine methylprednisol... pixantrone dima...	18 Years - 64 Years	National Cancer Institute (NCI)

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