Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Nutritional and Metabolic Diseases

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Amyloidosis

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Proteostasis Deficiencies

Metabolic Diseases

AL Amyloidosis

Antineoplastic Agents

All Drugs and Chemicals

Melphalan

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

Immunologic Factors

Test Dose CE Melphalan 10mg/m2 with PK studies Day -12 to Day-3, CE Melphalan Dose of Target AUC 13 mg/L/h infused with PK studies Day -2, 3-10 x 10\^6 CD 34+ cells/kg reinfused Day 0, Pegfilgrastim 6mg injection Day +1

Pegfilgrastim

Autologous Hematopoietic Progenitor Cell Transplant

Heather Landau, MD

Captisol Enabled Melphalan, is a new formulation of the standard of care melphalan chemotherapy that in packaged in an inactive substance that is believed to help the chemotherapy be more stable (meaning that it doesn't lose its effect or need to be administered quickly after being mixed). It may also have fewer side effects such as problems with important levels of body electrolytes such as potassium, phosphorous and magnesium; and cause less kidney and heart damage\] than standard formulation melphalan.

The purpose of this study is to determine if the investigators can achieve a certain level of Captisol Enabled Melphalan that would be best to use in treating Multiple Myeloma and AL Amyloidosis.

Study of Captisol Enabled Melphalan and Pharmacokinetics for Patients With Multiple Myeloma or Light Chain Amyloidosis That Are Receiving an Autologous Transplant.

Pharmacokinetic (PK)-Directed Dosing of Captisol Enabled Melphalan for Patients With Multiple Myeloma or Light Chain (AL) Amyloidosis Undergoing High Dose Therapy and Autologous Hematopoietic Progenitor Cell Transplant

defined as stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR), or Partial Response (PR) to high-dose CE melphalan in patients enrolled in the study between days 90-100 post-AHCT. Responses will be evaluated by the IMWG Response Criteria and Minor Response (MR) criteria. Responses will be evaluated by the standard AL Amyloid Organ Response Criteria.

Spectrum Pharmaceuticals, Inc

Memorial Sloan Kettering Cancer Center

Lymphoma

Lymphatic Diseases

Lymphosarcoma

Antirheumatic Agents

Rituximab

Antineoplastic Agents, Immunological

Rituximab and DexaBEAM

Georg Hess, MD

The investigator prospectively evaluated the combination of Rituximab and Dexa-BEAM (dexamethasone, carmustine, etoposide, cytarabine, melphalan) followed by high dose therapy in patients with relapsed/refractory aggressive and indolent lymphoma.

This study was a prospective, open label, single arm multicenter phase II study. It was approved by the ethics committees of the participating centers, and all regulatory issues and the principles of GCP were followed. The study was initiated in 2002, and recruitment closed in 2006. Final data analysis was performed in 3/2013. The trial had been registered at the clinical trial database of the CIMT consortium The overall treatment plan in brief, eligible patients were treated with two cycles of R-DexaBEAM in a 3-4 week interval, and stem cell mobilization was scheduled after the second cycle. Mobilization after the first cycle was allowed if the patient had received extensive prior therapy and if no evidence of BM-involvement was found. HDT was scheduled within 4-8 weeks after the last R-DexaBEAM cycle in patients achieving at least PR.

Protocols: The applied chemotherapy protocols were as follows: The salvage/mobilization-regimen consisted of R-DexaBEAM: Rituximab 375mg/m² d1, dexamethasone 24 mg t.i.d p.o., d 1-10; BCNU 60mg/m² i.v., d 2; etoposide 75mg/m² i.v., d 4-7; cytarabin 200mg/m² b.i.d i.v., d 4-7 in 2 doses; melphalan 20mg/m² i.v., d3. For high dose radio/chemotherapy, two different conditioning regimens were defined in the protocol: chemo-radiotherapy R-TBI/Cy consisted of Rituximab 375mg/m² i.v. d -7, -2, fractionated total body irradiation with 12 Gy, d -6 to -4; and cyclophosphamide 60 mg/kgbw i.v., day -3 to -2.

The chemotherapy protocol used for conditioning was R-BEAM: Rituximab 375mg/m² i.v. d -8, -2, BCNU 300mg/m² i.v., d -7; cytarabin 400mg/m² b.i.d. i.v., d -6 to -3; etoposide 200mg/m² i.v. b.i.d., d -6 to -3; melphalan 140mg/m² i.v., d -2.

Stem cell mobilization: Following mobilization chemotherapy, stem cells were collected after G-CSF stimulation (5-10µg/kg bw/d, starting on day 11 after R-DexaBEAM) using standard apheresis procedures, and stem cells were processed and cryopreserved according to local standards. A minimum number of 2x106/kgbw CD34 positive cells were required for the conduct of high dose therapy.

Autologous stem cell transfusion: For stem cell rescue after HDT, at least 2x106/kg CD34 positive cells were applied. Stem cells were thawed at bedside and infused via central venous catheter.

Concomitant treatments were conducted according to local standards, e.g. for antiemetic prophylaxis, hydration and parenteral nutrition. At the time of trial initiation, a prophylactic antibiotic treatment was recommended due to local standards, e.g. ciprofloxacin. For PJP prophylaxis co-trimoxazole was mandatory until recovery to a CD4-cell count of 200/µl had been reached or until day 100 post stem cell re-transfusion. In cases of symptomatic CMV-reactivation, treatment with ganciclovir was recommended. In addition, maintenance of immunoglobulin levels at concentrations \>5g/l was recommended. G-CSF support was optional after salvage or high dose therapy (5µg/kgbw).

Diagnostic evaluation: Throughout the entire treatment, routine laboratory investigations were performed. In addition, CMV-reactivation screening was mandatory in CMV positive patients. staging procedures including CT-scans were scheduled at baseline, prior to HDT and 2, 6, 9, 12, 18, 24, 36 months after HDT, and thereafter as clinically indicated. Responses were assessed using the criteria of Cheson et al. BM was evaluated at baseline, and re-evaluation was only needed to confirm complete remission.

Statistical analysis The primary efficacy endpoint of the study was progression-free survival (PFS), as calculated for the intent-to-treat population. Event-free survival was defined as the time from the date of trial inclusion to the time of either disease progression or death (irrespective of cause) or the latest follow-up without progression.

Secondary efficacy endpoints were overall response rate at day 60 post stem cell re-transfusion, overall survival (time from inclusion to death, irrespective of cause), safety and side effects, toxicity of high dose therapy according to Bearman score, and number of CMV-reactivations. Further endpoints, which will be reported separately, were the percentage of patients being negative for minimal residual disease (MRD) by either t(14;18) - FL or t(11;14) - MCL PCR, time to immune reconstitution with achievement of a CD4 count of 200/µl.

Results for time-to-event endpoints were analysed according to Kaplan-Meier estimator, and comparisons were performed with the log-rank test. P \<0.05 was considered statistically significant. GraphPad Prism version 5.0 for Windows, (GraphPad Software, CA, USA) was used for all calculations. Statistical advice was given by the Institute of Epidemiology and Biometrical Statistics at the University of Mainz.

Rituximab and DexaBEAM as Salvage Therapy for Relapsed Lymphoma

Eine Phase II Studie Zur Beurteilung Der Wirksamkeit Von Rituximab in Der Salvage- Und Hochdosistherapie Mit Autologer Stammzelltransplantation Bei Patienten Mit B-Zell-Non-Hodgkin-Lymphom

Number of patients with Adverse Events; Side effects and toxicity of high dose therapy according to Bearman score; Treatment related mortality

PFS at 5 years in patients

* completing the entire protocol (PPP)
* intention to treat population (IIT)

Overall survival at five years and median overall survival

Roche Pharma AG

Klinikum Frankfurt Höchst

Head Study Department of the Department of Hem / Onc

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Dexamethasone

Lenalidomide

Bortezomib

Dexamethasone acetate

Angiogenesis Inhibitors

Growth Inhibitors

3 induction cycles of bortezomib, lenalidomide and dexamethasone (VRD) followed by high dose melphalan and autologous stem cell transplantation.

Two months after haematological recovery, patients will receive 2 consolidation cycles of VRD and maintenance therapy for 1 year with lenalidomide.

Induction:

3 cycles of 21 days of Dexamethasone : 40 mg/j, days 1, 8 et 14 Bortezomib (Velcade®) : 1,3 mg/m2/d, days 1, 4, 8, et 11 Lenalidomide (Revlimid®) :25 mg/d, days 1 to 14

Consolidation (2 months After ASCT):

2 cycles of 21 days of Lenalidomide (Revlimid®) 25 mg/j, days 1 à 14 Bortezomib (Velcade®) 1,3 mg/m2/d, days 1, 4, 8, et 11 Dexamethasone 40 mg/j, days 1, 8 et 14

Maintenance Phase:

3 to 8 weeks after consolidation. Cycle length: 28 days Lenalidomide (Revlimid®) 10 mg/d until 12 months

Lenalidomide, Bortezomib

Michel ATTAL, MD

The purpose of this Phase 2 study is to evaluate the efficacy and safety of treatment with bortezomib, lenalidomide and dexamethasone in patients with untreated multiple myeloma. This study will evaluate whether the addition of lenalidomide to bortezomib and dexamethasone will increase the Complete Response (CR)/ very good partial response (VGPR) rate before and after High Dose Therapy (HDT) with ASCT.

Patients will receive 3 induction cycles of bortezomib, lenalidomide and dexamethasone (VRD) followed by high dose melphalan and autologous stem cell transplantation. Two months after haematological recovery, patients will receive 2 consolidation cycles of VRD and maintenance therapy for 1 year with lenalidomide

Frontline Therapy in de Novo Multiple Myeloma Patients Under 65

IFM2008: Frontline Therapy in de Novo Multiple Myeloma Patients Under 65, (a Phase 2 Multicenter Trial)

Evaluate the best response achieved , according to the IMWG uniform criteria, after consolidation treatment.

Evaluate the complete and very good partial response rates of the combination of bortezomib, lenalidomide and dexamethasone in newly diagnosed multiple myeloma patients after 3 cycles.

Determine the safety and tolerability of the drug combination in this patient populations.

Evaluate the faisability and quality of the peripheral stem cells collection.

Evaluate the complete and very good partial response rates 2 months after HDT with ASCT and after 2 cycles of consolidation treatment.

Evaluate the progression free survival, the overall survival, time to progression and duration of response.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Captisol Enabled Melphalan and Pharmacokinetics for Patients With Multiple Myeloma or Light Chain Amyloidosis That Are Receiving an Autologous Transplant.	NCT02909036	Multiple Myelom... Amyloidosis	Melphalan Pegfilgrastim Autologous Hema...	18 Years - 75 Years	Memorial Sloan Kettering Cancer Center
Rituximab and DexaBEAM as Salvage Therapy for Relapsed Lymphoma	NCT02099292	Relapsed Non-Ho...	Rituximab and D...	18 Years - 65 Years	Johannes Gutenberg University Mainz
Frontline Therapy in de Novo Multiple Myeloma Patients Under 65	NCT01206205	Multiple Myelom...	Lenalidomide, B...	18 Years - 65 Years	University Hospital, Toulouse
Study of Captisol Enabled Melphalan and Pharmacokinetics for Patients With Multiple Myeloma or Light Chain Amyloidosis That Are Receiving an Autologous Transplant.	NCT02909036	Multiple Myelom... Amyloidosis	Melphalan Pegfilgrastim Autologous Hema...	18 Years - 75 Years	Memorial Sloan Kettering Cancer Center

Spots Global Cancer Trial Database for high dose therapy