Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Antineoplastic Agents

All Drugs and Chemicals

Topotecan

Melphalan

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

Immunologic Factors

Topoisomerase I Inhibitors

Enzyme Inhibitors

Participants 18 - 60 years of age. Intensive-Dose Melphalan and Topotecan (MT) followed by Stem Cell transplant.

Participants 61 years of age or older. Intensive-Dose Melphalan and Topotecan (MT) followed by Stem Cell transplant.

(Days -4,-3,-2) 50 mg/m\^2/day IV over 30 minutes (total dose 150 mg/m\^2)

melphalan

Phase I Dose Escalation: Level 1 - 20 mg/m\^2; Level 2 - 30 mg/m\^2; Level 4 - 54 mg/m\^2; Level 5 - 72 mg/m\^2; Level 6 - 96 mg/m\^2; Level 7 - 127.8 mg/m\^2; Level 8 - 170.1 mg/m\^2

Phase II: Treatment at maximum tolerated dose (MTD)

topotecan (TPT)

Autologous Stem Cell Rescue

Daniel M Sullivan, MD

The purpose of this research study is to determine the safest dose of topotecan when given in a high dose before a stem cell transplant; topotecan will be given with melphalan.

The stem cells being transplanted are cells found in the bone marrow and blood that are responsible for making red blood cells, white blood cells, and platelets. The stem cells are collected by a process called leukapheresis and will be frozen for later use. After receiving the chemotherapy drugs, the stem cells will be thawed and given like a blood transfusion. This is called autologous stem cell transplant or rescue. The study doctors will be measuring how well the disease responds to the drugs as well as any side effects to the drugs. During the course of this study, blood and bone marrow samples will be obtained to measure levels of the chemotherapy drugs as well as levels of certain enzymes (proteins).

The staff of the Blood and Marrow Transplant program will continue to collect information about the participant's disease and its treatment for the rest of their life.

Study of Melphalan and Topotecan (MT) Followed by Autologous Stem Cell Rescue in Patients With Multiple Myeloma.

A Study of Intensive-Dose Melphalan and Topotecan (MT) Followed by Autologous Stem Cell Rescue in Patients With Multiple Myeloma.

Evaluate the pharmacokinetic profiles of high dose topotecan and melphalan and to investigate the pharmacodynamic relationships with respect to the efficacy and toxicity of this regimen in each age group. Pharmacokinetics of Topotecan: For all dose levels, topotecan levels on Day -4 will be obtained at -15 min, 20 min into 30 min infusion, and 5 min, 15 min, 30 min, 1 h, 2 h, 4 h, 8 h, and 23 h after the 30 min infusion. Pharmacokinetics of Melphalan: For all dose levels, melphalan levels during the first day of cytoxan priming chemotherapy and on Day -4 will be obtained before, at the end of the infusion, and 5 minutes (min), 15 min, 30 min, 45 min, 60 min, 90 min, 120 min and 180 min after the infusion. The infusion time for the test dose of melphalan is over 5 min and for the high-dose is over 30 min.

Laboratory Correlates will be summarized using descriptive statistics.

BCRP function will be assayed in multiple myeloma patient bone marrow aspirates obtained before and during high dose chemotherapy. BCRP function is expressed as the change in relative fluorescence in topotecan versus control cells. The distribution of paired differences in BCRP, a continuous variable, will be summarized using descriptive statistics and will be correlated with response and toxicity.

MTD of topotecan in multiple myeloma patients receiving autologous transplant when give with melphalan 150 mg/m\^2 for three days. Two parallel dose escalations were used, one each for young (18-60 years of age) and elderly patients (\> 61 years of age). Elderly patients began a dose level once it had been found to be safe for the young cohort. The purpose of this approach was to expand the access of this trial to elderly patients while ensuring safety.

Phase I Dose Escalation: Level 1 - 20 mg/m\^2; Level 2 - 30 mg/m\^2; Level 4 - 54 mg/m\^2; Level 5 - 72 mg/m\^2; Level 6 - 96 mg/m\^2; Level 7 - 127.8 mg/m\^2; Level 8 - 170.1 mg/m\^2

Re-evaluation of participants who had responsive disease prior to transplant. All changes in monoclonal protein and immunoglobulins will be referenced to those levels obtained immediately prior to cyclophosphamide priming chemotherapy. Complete Response (CR): A CR will be defined as the disappearance of the monoclonal protein by immunofixation studies of serum and urine (100x concentrate) and less than or equal to 5% plasma cells in a bone marrow aspirate. Partial Response (PR): 50% - 74% decrease in the measurable monoclonal protein (M-component from an SPEP and/or UPEP with immunofixation).

Time to treatment failure, which is defined as the time from day 0 to the time of progressive disease. Progressive disease is defined by unequivocal objective evidence and constitutes any of the following: 1). an increase in the total amount of monoclonal protein (M-component from Serum Protein Electrophoresis (SPEP) and/or Urine Protein Electrophoresis (UPEP) with immunofixation) by more than 100% from the lowest level of serum myeloma protein seen after high-dose chemotherapy by serum protein electrophoresis; 2). an increase in the total amount of monoclonal protein above the remission level of the myeloma peak (i.e., an increase of \>25% above the lowest level in a 24 hour urine or serum protein; 3). the reappearance of the M-protein if the patient had entered a CR: 4). definite increase in the size (\> 1 cm) or number of lytic bone lesions. Compression fractures do not constitute a relapse.

Time from start of treatment until death from any cause.

GlaxoSmithKline

National Cancer Institute (NCI)

H. Lee Moffitt Cancer Center and Research Institute

Participants 18 - 60 years of age. Intensive-Dose Melphalan and Topotecan (MT) followed by Stem Cell transplant.

melphalan: (Days -4,-3,-2) 50 mg/m\^2/day IV over 30 minutes (total dose 150 mg/m\^2)

topotecan (TPT): Phase I Dose Escalation: Level 1 - 20 mg/m\^2; Level 2 - 30 mg/m\^2; Level 4 - 54 mg/m\^2; Level 5 - 72 mg/m\^2; Level 6 - 96 mg/m\^2; Level 7 - 127.8 mg/m\^2; Level 8 - 170.1 mg/m\^2

Phase II: Treatment at maximum tolerated dose (MTD)

Autologous Stem Cell Rescue: Day 0

Age Group A - Melphalan and Topotecan Plus Stem Cell Rescue

Participants 61 years of age or older. Intensive-Dose Melphalan and Topotecan (MT) followed by Stem Cell transplant.

melphalan: (Days -4,-3,-2) 50 mg/m\^2/day IV over 30 minutes (total dose 150 mg/m\^2)

topotecan (TPT): Phase I Dose Escalation: Level 1 - 20 mg/m\^2; Level 2 - 30 mg/m\^2; Level 4 - 54 mg/m\^2; Level 5 - 72 mg/m\^2; Level 6 - 96 mg/m\^2; Level 7 - 127.8 mg/m\^2; Level 8 - 170.1 mg/m\^2

Phase II: Treatment at maximum tolerated dose (MTD)

Autologous Stem Cell Rescue: Day 0

Age Group B - Melphalan and Topotecan Plus Stem Cell Rescue

Total

Age, Continuous

Age, Categorical

Sex: Female, Male

United States

Region of Enrollment

Participants: 177 included in Baseline; 129 included in Phase I Maximum Tolerated Dose Outcome; 51 Phase II participants with responsive disease prior to transplant were re-evaluated for the Overall Response Rate; 79 treated in Phase II and evaluable at time of analysis are included in the Event Free Survival and Overall Survival Outcome Measures.

Data on presence of chromosomal abnormalities at time of diagnosis were not available for majority of patients. The cancer center will continue to collect information about the participant's disease and its treatment for the rest of their life.

Daniel M. Sullivan, M.D.

Phase I - Maximum Tolerated Dose (MTD) Level

Overall Response Rate

Complete Response Rate

Partial Response Rate

Phase II (treatment at MTD) participants with responsive disease prior to transplant.

Phase II Participants - Overall Response Rate

Phase II (treatment at MTD) evaluable participants at time of analysis

Phase II Event Free Survival (EFS)

Phase II Overall Survival (OS)

Pharmacokinetic Profiles of High Dose Topotecan and Melphalan

Amount, Activity and Subcellular Distribution of Topoisomerase I With Clinical Response and Toxicity

DNA Topoisomerase I Amount, Activity, or Subcellular Distribution

Genomic DNA Sequence Variations and Correlate With Toxicity to Melphalan and Topotecan

Breast Cancer Resistance Protein (BCRP) Expression

Phase I: Dose Escalation

Phase II: Treatment at MTD

Plasmacytoma

Etoposide

Etoposide phosphate

Melphalan Topotecan Etoposide VP-16 Phosphate autologous stem cell transplant

Etoposide phosphate 1363 mg/m\^2/day IV over 4 hours (total dose 2726 mg/m\^2, or 2400 mg/m\^2 etoposide equivalents), beginning 24 hours after the completion of the last infusion of topotecan Days -4, -3

etoposide phosphate

Melphalan 50 mg/m\^2/day IV over 30 minutes (total dose 150 mg/m\^2), followed immediately by topotecan. Days -7, -6, -5

Topotecan 3.3 mg/m\^2/day (starting total dose = 10 mg/m\^2 for level 2) IV over 30 minutes. No topotecan will be administered on the first dose level Days -7, -6, -5

topotecan

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of combination chemotherapy plus peripheral stem cell transplantation in treating patients who have multiple myeloma.

OBJECTIVES: I. Determine the toxicity and potential efficacy of intensive high dose chemotherapy consisting of melphalan, topotecan, and etoposide phosphate followed by autologous stem cell transplantation in patients with stage II or III multiple myeloma or stage I with evidence of progressive disease. II. Determine the maximum tolerated dose of topotecan in combination with melphalan and etoposide phosphate in this patient population. III. Determine response rates and time to treatment failure in these patients when treated with this regimen. IV. Determine the pharmacokinetic profiles of these drugs and investigate the pharmacodynamic relationships with respect to the efficacy and toxicity of this regimen in these patients. V. Determine whether the sequencing of this chemotherapy regimen is appropriate and optimal in these patients.

OUTLINE: This is a dose escalation study of topotecan. Patients are primed with cyclophosphamide IV over 2 hours for 2 days. Peripheral blood stem cells (PBSC) are collected. Approximately 4 weeks after PBSC collection, patients receive melphalan IV over 30 minutes and topotecan IV over 30 minutes on days -7 to -5. Etoposide phosphate IV is administered over 4 hours on days -4 and -3. PBSC are reinfused on day 0. Cohorts of 4-12 patients receive escalating doses of topotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 6 of 12 patients experience dose limiting toxicities. Patients are followed 2-3 times a week for approximately 1 month, then at 3, 6, and 12 months.

PROJECTED ACCRUAL: A total of 34-60 patients will be accrued for this study within 24-36 months.

Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma

A Study of Intensive-Dose Melphalan, Topotecan, and VP-16 Phosphate (MTV) Followed by Autologous Stem Cell Rescue in Patients With Multiple Myeloma

To determine the incidence and duration of CTCAE v3, grade 3 or 4 mucositis for modified dose level four.

SmithKline Beecham

Bristol-Myers Squibb

Neuroblastoma

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antirheumatic Agents

Cyclophosphamide

Carboplatin

Lenograstim

Thiotepa

Adjuvants, Immunologic

Consolidation course #1 consists of thiotepa and cyclophosphamide followed by a PBSC rescue. Consolidation course #2 consists of melphalan, etoposide and carboplatin followed by a second PBSC rescue. Post infusion, patients will receive Granulocyte-Colony Stimulating Factor beginning on Day 0 of each consolidation course.

Thiotepa by IV once daily for 3 doses on Days -7, -6 and -5. Given as part of Consolidation Course #1 along with Cyclophosphamide.

Cyclophosphamide by IV once daily for 4 doses on Days -5, -4, -3 and -2. Given as part of Consolidation Course #1 along with Thiotepa.

Melphalan by IV once daily for 3 doses on Days -8, -7, and -6. Given as part of Consolidation Course #2 along with Etoposide and Carboplatin.

Etoposide by IV once daily for 4 doses on Days -8, -7, -6 and -5. Given as part of Consolidation Course #2 along with Melphalan and Carboplatin.

Carboplatin by IV once daily for 4 doses on Days -8, -7, -6 and -5. Given as part of Consolidation Course #2 along with Etoposide and Melphalan.

On Day 0 the stem cells will be infused immediately after thawing over 15-60 minutes per institutional guidelines.

Autologous Stem Cell Infusion

Beginning on day 0 after infusion of the PBSC, patients will receive G-CSF SQ or IV (SQ preferred) 5 micrograms/kg once daily and continuing once daily until post-nadir ANC \> 2000/μL for 3 consecutive days.

Granulocyte colony stimulating factor

Lisa Burke

Ashish Gupta, MBBS, MPH

Lisa Burke, RN

This is a phase II single center study to administer two courses of myeloablative consolidation chemotherapy each followed by an autologous peripheral blood stem cell (PBSC) rescue in patients with high-risk neuroblastoma who have completed induction chemotherapy (independent of this study). Ideally, patients should begin consolidation chemotherapy no later than 8 weeks after the start of Induction Cycle #5; however it is strongly recommended to begin consolidation within 4-6 weeks after the start of Induction Cycle #5.

Myeloablative Consolidation Therapy and Tandem Autologous Stem Cell Rescue in Patients With High-Risk Neuroblastoma

Tandem Myeloablative Consolidation Therapy and Autologous Stem Cell Rescue for High-Risk Neuroblastoma

Percentage of patients with progression free survial. Kaplan-Meier curves and 95% confidence intervals will be used to estimate.

Defined as an absolute neutrophil count (ANC) greater than or equal to 0.5 x 109/L for three consecutive days by day 42 after first transplant.

Percentage of patients with relapse. Relapse will be defined as any new lesion; increase of any measurable lesion by \>25%; previous negative bone is positive.

Kaplan-Meier curves and 95% confidence intervals will be used to estimate overall survival.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Melphalan and Topotecan (MT) Followed by Autologous Stem Cell Rescue in Patients With Multiple Myeloma.	NCT00325416	Multiple Myelom...	melphalan topotecan (TPT) Autologous Stem...	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
Study of Melphalan and Topotecan (MT) Followed by Autologous Stem Cell Rescue in Patients With Multiple Myeloma.	NCT00325416	Multiple Myelom...	melphalan topotecan (TPT) Autologous Stem...	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma	NCT00005792	Multiple Myelom... Plasma Cell Neo...	etoposide phosp... melphalan topotecan Autologous Stem...	15 Years - 69 Years	H. Lee Moffitt Cancer Center and Research Institute
Myeloablative Consolidation Therapy and Tandem Autologous Stem Cell Rescue in Patients With High-Risk Neuroblastoma	NCT02605421	Neuroblastoma	Thiotepa Cyclophosphamid... Melphalan Etoposide Carboplatin Autologous Stem... Granulocyte col...	- 30 Years	Masonic Cancer Center, University of Minnesota

Spots Global Cancer Trial Database for autologous stem cell rescue