Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Behaviors and Mental Disorders

Rare Diseases

Lymphoma

Lymphoma, Follicular

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Aggression

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Follicular Lymphoma

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Antirheumatic Agents

Anti-Inflammatory Agents

Antiemetics

Neuroprotective Agents

Gastrointestinal Agents

Etoposide

Cytarabine

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Rituximab

Vincristine

Melphalan

Cisplatin

Prednisolone

Immunomodulating Agents

Lenograstim

Etoposide phosphate

Methylprednisolone

Methylprednisolone Acetate

Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

Prednisolone phosphate

Immunologic Factors

Intensive induction followed by high-dose consolidation with stem cell support ± radiotherapy

Given together with induction chemotherapy:

Rituximab - 375 mg/m2 iv every 3 weeks, 4-6 doses

immunotherapy

cyclophosphamide 3000 mg/m2 iv every 3 weeks, 3 cycles vincristin 2 mg iv every 3 weeks, 3 cycles doxorubicin 75 mg/m2 iv every 3 weeks, 3 cycles Prednisolone 300 mg/m2 divided into five days po every 3 weeks, 3 cycles pegfilgrastim 6 mg sc every 3 weeks.

3 cycles consisting of combination treatment of above mentioned drugs are given.

Induction treatment part 1

Starts three weeks after last cycle of Induction part 1.

Etoposide 240 mg/m2 divided into equal doses for four days, together with methylprednisolone 2000 mg divided into equal doses for four days, together with cisplatin 100 mg/m2 divided into equal doses for four days, and together with cytarabine 2000 mg/m2 iv one dose on 4th day of treatment. Filgrastim 10-12 ug/kg from day five after start of chemotherapy untill stem cell collection.

Peripheral blood progenitor cell collection (PBPC) is started when CD34 positive cells are \>20/cubic milimeter of blood and continued untill 5 million of CD34 positive cells are collected from peripheral blood.

Induction treatment part 2 with PBPC collection

Part 3 of induction treatment is given approximately one week after the end of Part 2.

Etoposide 240 mg/m2 divided into equal doses for four days, methylprednisolone 2000 mg divided into equal doses for four days, cisplatin 100 mg/m2 divided into equal doses for four days, cytarabine 2000 mg/m2 iv one dose on day 4 of chemotherapy and pegfilgrastim 6 mg on day five of chemotherapy are given twice three weeks apart.

Induction treatment part 3

Consolidation treatment Part 1 starts 4-8 weeks after the second cycle of Induction treatment Part 3.

High dose chemotherapy (HD-chemotherapy) consists of:

BCNU 300 mg/m2 is given on day 1, etoposide 800 mg/m2 divided into four equal doses is given on day 2-5, cytarabine 1600 mg/m2 divided into eight equal doses is given on day 2-5, melphalan 140 mg/m2 is given on day 6.

On day 7, collected stem cells from peripheral blood (see Induction treatment part 1) are infused back to the patient. This is called autologous transplantation (ASCT). Filgrastim 5 ug/kg is given from day 14 (start of the chemotherapy being day 1) until neutrophil recovery.

Consolidation treatment part 1: HD-chemotherapy with ASCT

Radiotherapy is started given 4-8 weeks after the autologous transplantation. It is given to patients with initially bulky disease (\>10 cm at diagnosis) or to patients with residual disease after Induction treatment part 1-3 and Consolidation treatment part 1. 30-40 Gy are given in 2 Gy fractions over 3-4 weeks.

Consolidation treatment part 2: Radiotherapy

Pytlik Robert, M.D.

Marek Trněný, M.D., PhD.

The purpose of this study is to show if addition of Rituximab to intensive induction (MegaCHOP/ESHAP) and high-dose consolidation (BEAM) improves progression-free and overall survival in patients younger than 65 years with aggressive B-cell lymphoma and aaIPI 2 or 3.

Previous study of Czech Lymphoma Study Group (4_2002)have shown that intensive induction (MegaCHOP - Cyclophosphamide 3 g/m2, Vincristine 2 mg, Adriamycin 75 mg/m2, Prednisone 300 mg/m2 every three weeks with G-CSF for three cycles, followed by ESHAP - Etoposide 240 mg/m2, Cisplatin 100 mg/m2, Solumedrol 2000 mg and cytarabine 2000 mg/m2 for three cycles every three weeks with G-CSF) followed by intensive consolidation (BEAM) and stem cell support improves progression-free survival in adult patients (18-65 years old) with aggressive B-cell lymphoma (namely, diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma and follicular lymphoma grade II) with aaIPI 2 and namely, with aaIPI 3. This study was aimed to find out if addition of four to six doses of Rituximab 375 mg/m2 on first day of every cycle of intensive induction further improves prognosis of these patients.

Inclusion criteria for this trial were:

* newly diagnosed aggressive B-cell lymphoma, namely diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma and follicular lymphoma grade III
* age 18-65 years
* age adjusted IPI (International Prognostic Index) score 2 or 3
* ECOG performance status 0-3
* signed informed consent

Exclusion criteria were:

* relapsed lymphoma
* previous treatment (up to one cycle of standard pretreatment - COP, CHOP or steroids was permitted and later became mandatory to decrease disease burden and/or improve the performance status of the patient)
* Burkitt lymphoma
* posttransplant lymphoproliferation
* CNS involvement
* other malignant tumor in previous history, except basalioma, skin squamocellular carcinoma or cervical carcinoma in situ
* other serious comorbidity

Primary endpoints was progression-free survival

Secondary endpoints were:

* rate of complete remission and overall response rate
* overall survival
* toxicity of the protocol, measured as grade III-IV toxicity and/or inability to finish the protocol as planned

Planned number of accrued patients was 100.

R-MegaCHOP-ESHAP-BEAM in Patients With High-Risk Aggressive B-Cell Lymphomas

Phase II Study of Intensive Induction (R-MegaCHOP/ESHAP)Followed By Intensive Consolidation (BEAM) In Treatment Of High-Risk Aggressive B-Cell Lymphomas

Ministry of Health, Czech Republic

Hoffmann-La Roche

Czech Lymphoma Study Group

Symptoms and General Pathology

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Disease Progression

Hematologic Diseases

Acute Graft Versus Host Disease

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Vosaroxin and Cytarabine

Hamid Sayar, MD

This is a pilot efficacy assessment clinical trial of vosaroxin and cytarabine for the treatment of adults 60 years of age or older with previously untreated acute myeloid leukemia. A total of 17 evaluable patients are planned to be treated on the study.

Primary objective: rate of complete remission (morphologic complete remission or morphologic complete remission with incomplete blood count recovery) Secondary objectives: (1) safety of this combination in induction therapy of older patients previously unexposed to intensive chemotherapy; (2) progression-free survival; (3) length of stay in hospital for induction; (4) 30- and 60-day mortality rate.

The treatment period will include up to 4 cycles of treatment (induction 1, induction 2, consolidation 1, and consolidation 2). In each cycle, the first day of study treatment will be considered day 1.

* Each cycle will include vosaroxin treatment on days 1 and 4 (total of 2 days) and cytarabine treatment on days 1-5 (total of 5 days) followed by a variable interval required to achieve hematologic recovery, defined as absolute neutrophil count (ANC) \> 1000 cells/L.
* Up to 2 cycles of consolidation treatment may be completed by eligible patients in remission (morphologic complete remission or morphologic complete remission with incomplete blood count recovery) if safety parameters are met.

Study of Vosaroxin and Cytarabine for the Treatment of Adults 60 Years of Age or Older With Previously Untreated AML

Pilot Study of Vosaroxin and Cytarabine for the Treatment of Adults 60 Years of Age or Older With Previously Untreated AML

Percentage of patients who have complete remission as defined by the International Working Group for AML: morphologic complete remission (CR) or morphologic complete remission with incomplete blood count recovery (CRi or CRp)

Number of unique patients who had a procedure or treatment related (possible, probable or definite) adverse events. (graded per NCI CTC v4.0)

Hamid Sayar

Assistant Professor of Clinical Medicine, Hematology/Oncology

Each cycle will include vosaroxin treatment on days 1 and 4 (total of 2 days) and cytarabine treatment on days 1-5 (total of 5 days) followed by a variable interval required to achieve hematologic recovery, defined as absolute neutrophil count (ANC) \> 1000 cells/L

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Due to the death of 2 patients which raised safety concerns, the study was closed with 2 patients enrolled.

All patients receiving at least one dose of study drug and having at least one evaluable post-baseline visit

Rate of Complete Remission

All patients enrolled and received treatment

Procedure or Procedure Related Adverse Events

Overall Study

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Idarubicin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Idarubicin dose intensification for remission induction in acute myeloid leukemia

In the phase I study, idarubicin dose is increased step by step as follows: 12 mg/m2/day for 3 days IV in the 1st step; 15 mg/m2/day for 3 days IV in the 2nd step; 18 mg/m2/day for 3 days IV in the 3rd step.

In the phase II study, idarubicin dose is the maximum tolerated dose that is determined from the phase I study or 18 mg/m2/day for 3 days .

Mark H Lee, M.D., Ph.D.

The purpose of this study is to determine whether idarubicin dose intensification is safe and effective as a remission induction therapy for acute myeloid leukemia.

Up to nowadays, a standard induction therapy for acute myeloid leukemia(AML) has consisted of cytarabine 100-200 mg per square meter of body surface area(BSA) per day continuous infusion for 7 days with idarubicin 12 mg per square meter or daunorubicin 45 mg per square meter of BSA per day for 3 days. This standard therapy induces a complete remission(CR) in 50-75% of young adults and 40-50% of older adults. Recently two cooperative groups prospectively compared 45 mg per square meter of daunorubicin to 90 mg per square meter of BSA. They reported high-dose daunorubicin, as compared with a standard dose one, resulted in a significantly higher CR rate and improved overall survival(OS) up to age 65 without additional toxic effects.

Daunorubicin has been more commonly used anthracycline; however, idarubicin has a longer intracellular retention time and has shown more rapid clearance of marrow blasts. In the early 1990, three prospectively randomized studies showed that a combined regimen of idarubicin and cytarabine was superior to one of daunorubicin and cytarabine for the induction therapy of AML in adults. When they compared daunorubicin 45-50 mg per square meter with idarubicin 12-13 mg per square meter for induction therapy, there were no significant differences in hematologic and non-hematologic toxicities, including cardiac toxicity.

Phase I studies of idarubicin in patients with acute leukemia and chronic myelogenous leukemia in blast crisis reported the dose-limiting toxicities(DLT) were stomatitis and anorexia at the maximum tolerated dose(MTD) of 15 mg per square meter of BSA per day for 3 days. Based on the results of these studies, the investigators have generally administered idarubicin 12 mg per square meter per day for 3 days for the remission induction therapy of AML. Meanwhile Sanz et al. had administered idarubicin 12 mg per square meter per day for 4 days in patients with acute promyelocytic leukemia, and Tedeschi et al. had done a single high-dose idarubicin 40 mg per square meter combined with high-dose cytarabine 3 g per square meter per day for 5 days in patients with acute lymphoblastic leukemia, with no significant increase of severe toxicity. The MTD of idarubicin should be reevaluated in the treatment of acute leukemia, especially in the era of granulocyte colony-stimulating factor and better supportive care available.

In this phase I study, idarubicin 12 mg per square meter of BSA per day for 3 days will be given to three patients at the first stage and then the idarubicin dose will be increased by 3 mg per square meter of BSA each stage. The phase I study consists of 3 stages and the idarubicin dose will be increased up to 18 mg per square meter of BSA per day for 3 days unless DLTs do not develop in more than 33% of enrolled patients at each stage. In the subsequent phase II study, the MTD being determined from the phase I study or 18 mg per square meter of idarubicin will be given to the enrolled patients. There were three large studies which enrolled a total of 942 previously untreated adult patients with AML and in which idarubicin 12-13 mg per square meter of BSA per day for 3 days and cytarabine 100 mg per square meter daily for 7 days were administered intravenously. Therefore, the investigators can adopt them as historical control groups in terms of statistical assessment.

In conclusion, the investigators desire to determine the safety and effectiveness of the intensified dose of idarubicin in the treatment of acute myeloid leukemia through this phase I and II study.

Safety and Efficacy Study of Idarubicin Dose Intensification to Treat Acute Myeloid Leukemia

Phase I/II Clinical Study of Idarubicin Dose Intensification for Remission Induction Therapy in Acute Myeloid Leukemia Patients Age of 65 Years or Less

The study design is adopted from traditional 3+3 design for phase I cancer clinical trials. The first three patients are treated at a starting dose (level 1). If none of the three patients experiences a DLT(dose-limiting toxicity), another group of three patients will be treated at the next higher dose level. However, if one of the first three patients experiences a DLT, three more patients will be treated at the same dose level. The dose increment continues until at least two patients among a cohort of three to six patients experience DLTs.The maximum tolerated dose is defined as the dose level just below this toxic dose level.

A complete remission designation requires that the patient achieve the morphologic leukemia-free state and have an absolute neutrophil count of more than 1000 per microliter and platelets of more than 100000 per microliter. Hemoglobin concentration or hematocrit has no bearing on remission status, although the patient must be independent of transfusions.

Hematologic dose limiting toxicities (DLTs) are defined as the time to recovery of neutrophils (absolute neutrophil count of more than 500 per microliter) or platelets (platelet count of more than 20000 per microliter) exceeding 42 days after the start of induction therapy. Non-hematologic DLTs are defined as grade 4 or 5 toxicities.

Event-free survival is defined for all patients and measured from the date of entry on study. It is measured until treatment failure, relapse from CR, or death from any cause, whichever occurs first. Overall survival is defined for all patients in a trial, and measured from the date of entry onto a study until death from any cause. For a patient who is not known to have died by the end of study follow-up, observation of OS is censored on the date he or she was last known to be alive.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
R-MegaCHOP-ESHAP-BEAM in Patients With High-Risk Aggressive B-Cell Lymphomas	NCT00558220	Diffuse Large B... Primary Mediast... Follicular Lymp...	immunotherapy Induction treat... Induction treat... Induction treat... Consolidation t... Consolidation t...	18 Years - 65 Years	Czech Lymphoma Study Group
Study of Vosaroxin and Cytarabine for the Treatment of Adults 60 Years of Age or Older With Previously Untreated AML	NCT02485353	Leukemia, Myelo...	Vosaroxin and C...	60 Years -	Indiana University
Safety and Efficacy Study of Idarubicin Dose Intensification to Treat Acute Myeloid Leukemia	NCT01518556	Leukemia, Myelo...	Idarubicin	20 Years - 65 Years	Konkuk University Medical Center

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