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

All Drugs and Chemicals

Hyaluronic Acid

r/r multiple myeloma patients be treated with a split doses of LCAR-B38M cells. Total dose of 0.5-5 millions /kg cells will be administered at day 0, day 2 and day 6 by split dose (20%, 30% and 50% respectively).

LCAR-B38M CAR-T cell injection

This is a single arm, open-label, multi-center, phase 1/2 study, to determine the safety and efficacy of LCAR-B38M CAR-T cells in treating patients diagnosed with refractory/relapsed multiple myeloma (r/r MM).

Multiple myeloma (MM) is a usually incurable malignancy of plasma cells. Current therapies for multiple myeloma often cause remissions, but nearly all patients eventually relapse and die, an clear unmet clinical needs. As early as mid-2014, the investigators have started to develop a series of proprietary CAR-T products to target B cell maturation antigen (BCMA), a cell surface molecule which the investigator believes to be a desirable target antigen for multiple myeloma. All pre-clinical data and CMC data for LCAR-B38M CAR-T cell technology has been established by mid-2015 and a phase I proof-of-concept clinical trial has been planned since then.

LCAR-B38M Cells in Treating Relapsed/Refractory (R/R) Multiple Myeloma

A Clinical Study of Legend Biotech BCMA-chimeric Antigen Receptor Technology in Treating Relapsed/Refractory (R/R) Multiple Myeloma Patients

\>= Grade 1 signs/symptoms, laboratory toxicities, and clinical events) that are possibly, likely, or definitely related to study treatment

by measuring the changes of aberrant immunoglobulin in serum

Second Affiliated Hospital of Xi'an Jiaotong University

Ruijin Hospital

Jiangsu Provincial People's Hospital

Shanghai Changzheng Hospital

Nanjing Legend Biotech Co.

Antineoplastic Agents

Antirheumatic Agents

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

In this study, autologous T cells transduced with a BCMA-targeted chimeric antigen receptor (CAR-BCMA T cells) are used to treat patients with refractory or relapsed multiple myeloma.

Route of administration: Intravenous injection.

Lymphodepletion conditioning:

Lymphodepletion will be conducted several days prior to CAR-BCMA T cells infusion.

A combination of fludarabine and cyclophosphamide will be used for lymphodepletion.

Single dose of CAR-BCMA T cells will be infused, and classic "3+3" dose escalation will be applied.

CAR-BCMA T cells

Cyclophosphamide is used for lymphodepletion.

Siguo Hao, MD

A single arm, open-label pilot study is designed to determine the safety, efficacy and cytokinetics of CAR-BCMA T cells in patients with BCMA-positive refractory or relapsed multiple myeloma.

This study is designed to determine the safety, tolerability and engraftment potential of anti-BCMA lentivirus-transduced autologous T cells in patients with refractory or relapsed multiple myeloma.

Primary objectives:

1. Determine the safety and tolerability of CAR-BCMA T cells (autologous T cells transduced with chimeric antigen receptors recognizing BCMA) in patients with refractory or relapsed multiple myeloma.
2. Observe the cytokinetics of CAR-BCMA T cells.

Secondary objectives:

1. Observe the anti-tumor response of CAR-BCMA T cells to refractory or relapsed multiple myeloma (evaluated by diagnostic criteria International Myeloma Working Group (IMWG2014 version) as CR, sCR, ICR, MCR or VGPR).
2. Make an evaluation on the distribution and in vivo survival of CAR-BCMA T cells in peripheral blood, lymph node, and bone marrow.
3. Observe the immunogenicity of CAR-BCMA T cells, and determine if there is anti-BCMA scFv cellular immune response and anti-BCMA scFv humoral immune response.
4. Observe the changes of cell subsets of CAR-BCMA T cells against T cells (Tcm, central memory T lymphocytes; Tem, effector memory T lymphocytes; Treg, regulatory T lymphocytes).

Clinical Study of CAR-BCMA T Cells in Patients With Refractory or Relapsed Multiple Myeloma

Clinical Study of Redirected Autologous T Cells With a BCMA-targeted Chimeric Antigen Receptor in Patients With Refractory or Relapsed Multiple Myeloma

The number of DNA copies of CAR-BCMA T cells in lymph node samples or bone marrow samples at regular intervals from 24 hours after the initial infusion.

Detect titer of anti-BCMA anti-drug antibody (ADA).

Observe the changes of cell subsets of CAR-BCMA T cells against T cells (Tcm, central memory T lymphocytes; Tem, effector memory T lymphocytes; Treg, regulatory T lymphocytes).

Number of participants with study related adverse events which are defined as laboratory toxicities and clinical events that are possible, likely or definitely related to study treatment at any time from the infusion until week 24, including infusion related toxicity and any toxicity possibly related to CAR-BCMA T cells.

Duration of in vivo survival of CAR-BCMA T cells is defined as "engraftment". The primary engraftment endpoint is the number of CAR-BCMA DNA vector copies per mL blood of CAR-BCMA T cells at regular intervals from 24 hours after initial infusion through 2 years of last infusion. PCR for CAR-BCMA T vector sequences will be performed until any 2 sequential tests are negative, documented as engraftment of CAR-BCMA T cells.

Observe the anti-tumor response of CAR-BCMA T cells to refractory or relapsed multiple myeloma (evaluated by diagnostic criteria International Myeloma Working Group (IMWG2014 version) as CR, sCR, ICR, MCR or VGPR).

Statistical parameter#Progression-free Survival (PFS)

Statistical parameter:Disease Control Rate (DCR)

Statistical parameter:Objective Remission Rate (ORR)

Statistical parameter:Overall survival (OS)

CARsgen Therapeutics Co., Ltd.

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Antibodies

Antibodies, Monoclonal

Dexamethasone

Bortezomib

Dexamethasone acetate

Immunoglobulins

Siltuximab

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Siltuximab 6 milligram per kilogram (mg/kg) will be administered as intravenous infusion once every 2 weeks along with bortezomib 1.3 milligram per square meter (mg/m\^2) during cycle 1.

Bortezomib 1.3 mg/m\^2 will be administered as intravenous bolus on Days 1, 4, 8, 11, followed by a 10-day rest period; and on Days 22, 25, 29, and 32 followed by a 10-day rest period along with matching placebo administered as intravenous infusion once every 2 weeks during 42-day treatment phase. Bortezomib 1.3 mg/m\^2 will be administered as intravenous bolus on Days 1, 8, 15, 22 followed by a 13-day rest period (cycle Days 23 to 35) along with matching placebo once every 2 weeks during 35-day Maintenance Phase. Dexamethasone tablet will be administered at first occurrence of documented disease progression or if bortezomib was discontinued due to intolerable toxicity. Dexamethasone 40 milligram per day (mg/day) will be administered on days 1-4, 9-12, and 17-20 for four 28-day cycles then 40 mg/day for Days 1-4 for all subsequent cycles.

Bortezomib 1.3 mg/m\^2 will be administered as intravenous bolus on Days 1, 4, 8, 11, followed by a 10-day rest period; and on Days 22, 25, 29, and 32 followed by a 10-day rest period along with Siltuximab administered as intravenous infusion once every 2 weeks during 42-day treatment phase. Bortezomib 1.3 mg/m\^2 will be administered as intravenous bolus on Days 1, 8, 15, 22 followed by a 13-day rest period (cycle Days 23 to 35) along with Siltuximab administered as intravenous infusion once every 2 weeks for 35-day Maintenance Phase. Dexamethasone tablet will be administered at first occurrence of documented disease progression or if bortezomib was discontinued due to intolerable toxicity. Dexamethasone 40 mg/day will be administered on days 1-4, 9-12, and 17-20 for four 28-day cycles then 40 mg/day for Days 1-4 for all subsequent cycles.

Siltuximab 6 mg/kg will be administered as intravenous infusion once every 2 weeks during cycle 1 in Part 1. Siltuximab 6 mg/kg will be administered as intravenous infusion once every 2 weeks during 42-day Treatment Phase and 35-day Maintenance Phase in Part 2.

Bortezomib 1.3 mg/m\^2 will be administered as intravenous bolus once every 2 weeks during cycle 1 in Part 1. Bortezomib 1.3 mg/m\^2 will be administered as intravenous bolus on Days 1, 4, 8, 11, followed by a 10-day rest period; and on Days 22, 25, 29, and 32 followed by a 10-day rest period during 42-day treatment phase in Part 2. Bortezomib 1.3 mg/m2 will be administered as intravenous bolus on Days 1, 8, 15, 22 followed by a 13-day rest period (cycle Days 23 to 35) during 35-day Maintenance Phase in Part 2.

Matching placebo will be administered as intravenous infusion once every 2 weeks during 42-day treatment phase and 35-day maintenance phase in Part 2.

Placebo

Dexamethasone tablet will be administered in this study at the first occurrence of documented disease progression or if bortezomib was discontinued due to intolerable toxicity. Dexamethasone 40 mg/day will be administered on days 1-4, 9-12, and 17-20 for four 28-day cycles then 40 mg/day for Days 1-4 for all subsequent cycles in treatment phase and maintenance phase of Part 2.

Janssen Research & Development, LLC Clinical Trial

The purpose of Part 1 of the study is to determine the safety of the combination of Siltuximab (CNTO 328) and bortezomib (Velcade). The purpose of Part 2 of the study is to compare the length of progression free survival for those patients given CNTO 328 and bortezomib to those patients given bortezomib alone.

The purpose of this study is to see what effects CNTO 328 has on relapsed or refractory multiple myeloma. The study drug, CNTO 328, is a chimeric (part mouse) antibody (small protein that is important for fighting infection).CNTO 328 blocks a small protein called Interleukin 6 (IL-6). IL-6 is made naturally by your body, and at normal levels is important for inflammatory response. High levels of IL-6 can help cancer cells grow and interfere with chemotherapy drugs killing cancer cells. Cancer-related sickness such as cachexia (weight loss), bone resorption (weakening of your bones), and depression have been linked to high levels of IL-6. CNTO 328 has been shown to slow down tumor growth or shrink tumors when tested in animals. In other clinical trials, over 100 patients have received CNTO 328. There are studies ongoing in participants with kidney cancer, hematologic malignancies (blood cancers such as multiple myeloma), and prostate cancer, to see if CNTO 328 is safe and to see what effects it has on these types of cancer. At this time, it is unknown what effect CNTO 328 has had on the participants' cancer. Bortezomib is a type of drug known as a "proteasome inhibitor." A proteasome is a substance that is found in every cell and it is there to help to break down other substances ('proteins') and has a role in the way cells divide. If the proteasome is inhibited, it cannot perform its function in the cell, and if a cell cannot divide it dies. Over 8000 patients with multiple myeloma and other types of cancer have been treated with bortezomib. Bortezomib has been extensively studied in patients with previously treated multiple myeloma. Based on its established activity in pretreated multiple myeloma, bortezomib is registered in the United States and in Europe for the treatment of multiple myeloma patients who have received at least two prior therapies and have demonstrated disease progression on the last therapy. Bortezomib is currently also being studied in several other cancer types.This study consists of two parts. The purpose of Part 1 is to determine the safety of CNTO 328 and bortezomib when given together as a treatment. The purpose of Part 2 is to compare the safety and effects (good and bad) of the combination of CNTO 328 and bortezomib to the safety and effects of bortezomib alone. About 20 patients will take part in the first part of the study. About 270 patients will take part in the second part of the study at approximately 70 sites in the US, Canada, and Europe. Patients will be in the study for about 12 months, with a follow-up period of around 9 months. The study is divided into four different phases: Screening phase-which lasts up to 4 weeks. During this phase the study doctor will perform tests to see if the patient can participate in the study.Treatment phase-which may last up to 4 cycles of 42 days each during which the patient will be treated with CNTO 328 and bortezomib. Maintenance phase-If the patient benefits from the therapy in the treatment phase, the patient will continue to receive CNTO 328 and bortezomib, but now in cycles of 35 days each. Follow up phase, this includes an end of treatment visit 4 weeks after the patient's last infusion and follow up visits every three months until the patient starts a new anti-cancer treatment. CNTO 328 6mg/kg ( 6 milligrams per kilogram of body weight) will be given intravenously (into the vein) over 2 hours once every 2 weeks. Patients who respond with stable disease or better may receive additional doses. Bortezomib will be given IV (into the vein) at 1.3 mg/m2 over 3-5 seconds twice a week for 2 weeks followed by 1 week of rest.

A Study of the Safety and Efficacy of CNTO 328 and Bortezomib to Bortezomib Alone in Patients With Relapsed or Refractory Multiple Myeloma

A Phase 2, Randomized, Double-blind, Placebo-controlled Study Comparing the Combination of CNTO 328 (Anti-IL-6 Monoclonal Antibody) and Velcade Versus Velcade Alone in Subjects With Relapsed or Refractory Multiple Myeloma

Progression-free survival was defined as the time interval between randomization and the first documented sign of disease progression (including relapse from complete response \[CR\]) by the European Bone Marrow Transplant (EBMT) criteria or death, whichever occurred first. Relapse from CR requires at least 1 of the following: Reappearance of serum or urinary M-protein on immunofixation or routine electrophoresis, confirmed by at least 1 further investigation and excluding oligoclonal immune reconstitution; Greater than or equal to (\>=) 5 percent (%) plasma cells either in a bone marrow aspirate or on trephine bone biopsy; Development of new lytic bone lesions or soft tissue plasmacytomas or definite increase in the size of residual bone lesions (development of a compression fracture does not exclude continued response and may not indicate progression); Development of hypercalcemia not attributable to any other cause.

An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; lifethreatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

Overall response rate was defined as best response (CR/PR confirmed) for a participant recorded from first administration of study agent or randomization (Part 2) until disease progression/recurrence and before dexamethasone was added. CR: Absence of original M-protein in serum/urine by immunofixation,maintained for minimum of 6 weeks. The presence of oligoclonal bands consistent with oligoclonal immune reconstitution does not exclude CR; Less than 5 percent (%) plasma cells in bone marrow aspirate and also on trephine bone biopsy if biopsy is performed; No increase in size/number of lytic bone lesions; Disappearance of soft tissue plasmacytomas. PR: Greater than or equal to (\>=) 50% reduction in level of serum M-protein, maintained for minimum of 6 weeks. Reduction in 24 hour urinary light chain excretion either by \>= 90% or to \< 200 mg, maintained for minimum of 6 weeks; \>= 50% reduction in size of soft tissue plasmacytomas; No increase in size/number of lytic bone lesions.

CR rate was defined as the percentage of participants who achieved a confirmed CR before dexamethasone was added. CR: Absence of original M-protein in serum/urine by immunofixation,maintained for minimum of 6 weeks. The presence of oligoclonal bands consistent with oligoclonal immune reconstitution does not exclude CR; Less than 5 percent (%) plasma cells in bone marrow aspirate and also on trephine bone biopsy if biopsy is performed; No increase in size/number of lytic bone lesions; Disappearance of soft tissue plasmacytomas.

Overall survival was defined as the interval between the first administration of study agent or randomization (Part 2) and the participant's death from any cause. For participants with unknown survival status as of the data cut-off date, overall survival was censored at the last date known to be alive.

Janssen Research & Development, LLC

The safety population included all participants who received at least 1 dose of study treatment in Part 1 or Part 2. Participants were analyzed as per actual treatment received.

Part 1 - Bortezomib + Siltuximab

Bortezomib 1.3 mg/m\^2 will be administered as intravenous bolus on Days 1, 4, 8, 11, followed by a 10- day rest period; and on Days 22, 25, 29, and 32 followed by a 10-day rest period along with matching placebo administered as intravenous infusion once every 2 weeks during 42-day treatment phase.

Bortezomib 1.3 mg/m\^2 will be administered as intravenous bolus on Days 1, 8, 15, 22 followed by a 13- day rest period (cycle Days 23 to 35) along with matching placebo once every 2 weeks during 35-day Maintenance Phase. Dexamethasone tablet will be administered at first occurrence of documented disease progression or if bortezomib was discontinued due to intolerable toxicity. Dexamethasone 40 milligram per day (mg/day) will be administered on days 1-4, 9-12, and 17-20 for four 28-day cycles then 40 mg/day for Days 1-4 for all subsequent cycles.

Part 2 - Bortezomib + Placebo

Bortezomib 1.3 mg/m\^2 will be administered as intravenous bolus on Days 1, 4, 8, 11, followed by a 10- day rest period; and on Days 22, 25, 29, and 32 followed by a 10-day rest period along with Siltuximab administered as intravenous infusion once every 2 weeks during 42-day treatment phase. Bortezomib 1.3 mg/m\^2 will be administered as intravenous bolus on Days 1, 8, 15, 22 followed by a 13-day rest period (cycle Days 23 to 35) along with Siltuximab administered as intravenous infusion once every 2 weeks for 35-day Maintenance Phase. Dexamethasone tablet will be administered at first occurrence of documented disease progression or if bortezomib was discontinued due to intolerable toxicity.

Dexamethasone 40 mg/day will be administered on days 1-4, 9-12, and 17-20 for four 28-day cycles then 40 mg/day for Days 1-4 for all subsequent cycles.

Part 2 - Bortezomib + Siltuximab

Total

Age, Continuous

Sex: Female, Male

Belgium

Brazil

Bulgaria

Canada

Czech Republic

France

Germany

Greece

Hungary

Netherlands

Poland

Portugal

Romania

Russian Federation

Spain

United Kingdom

United States

Region of Enrollment

Project Physician

Bortezomib 1.3 mg/m\^2 will be administered as intravenous bolus on Days 1, 4, 8, 11, followed by a 10- day rest period; and on Days 22, 25, 29, and 32 followed by a 10-day rest period along with matching placebo administered as intravenous infusion once every 2 weeks during 42-day treatment phase. Bortezomib 1.3 mg/m\^2 will be administered as intravenous bolus on Days 1, 8, 15, 22 followed by a 13- day rest period (cycle Days 23 to 35) along with matching placebo once every 2 weeks during 35-day Maintenance Phase. Dexamethasone tablet will be administered at first occurrence of documented disease progression or if bortezomib was discontinued due to intolerable toxicity. Dexamethasone 40 milligram per day (mg/day) will be administered on days 1-4, 9-12, and 17-20 for four 28-day cycles then 40 mg/day for Days 1-4 for all subsequent cycles.

Bortezomib 1.3 mg/m\^2 will be administered as intravenous bolus on Days 1, 4, 8, 11, followed by a 10- day rest period; and on Days 22, 25, 29, and 32 followed by a 10-day rest period along with Siltuximab administered as intravenous infusion once every 2 weeks during 42-day treatment phase. Bortezomib 1.3 mg/m\^2 will be administered as intravenous bolus on Days 1, 8, 15, 22 followed by a 13-day rest period (cycle Days 23 to 35) along with Siltuximab administered as intravenous infusion once every 2 weeks for 35-day Maintenance Phase. Dexamethasone tablet will be administered at first occurrence of documented disease progression or if bortezomib was discontinued due to intolerable toxicity. Dexamethasone 40 mg/day will be administered on days 1-4, 9-12, and 17-20 for four 28-day cycles then 40 mg/day for Days 1-4 for all subsequent cycles.

Intent-to-treat (ITT) population included all participants randomized in Part 2. Participants were analyzed as per initial randomization.

Progression-free Survival

Response-evaluable population:all participants in Part 2 with confirmed diagnosis of multiple myeloma and measurable,secretory disease:either serum M-protein 1 \>= gram per deciliter(g/dL)/urine M-protein \>200 mg per 24 hours,at study entry;had at least 1 study agent administration;at least 1 post-baseline disease assessment before dexamethasone.

Percentage of Participants With Best Confirmed Response of Complete Response (CR) or Partial Response (PR) (Overall Response Rate)

Percentage of Participants With Confirmed Complete Response (CR Rate)

ITT population included all participants randomized in Part 2. Participants were analyzed as per initial randomization.

Overall Survival

Adverse Events (AEs)

Serious Adverse Events (SAEs)

Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)

Overall Study

Doxorubicin

Liposomal doxorubicin

Lenalidomide

Angiogenesis Inhibitors

Growth Inhibitors

Revlimid

Ralf Bargou, MD

This is a multi-center, open label, uncontrolled, non-comparative phase I/II study in patients with refractory or relapsed multiple myeloma who are eligible for second, third, or fourth line therapy. Patients will be enrolled sequentially into four dose cohorts. The feasibility of administrating Revlimid (R) in combination with Doxorubicin and Dexamethasone (AD) and the MTD of the combination will be determined in the phase I part of the study (Part A). When the MTD has been established, the efficacy of the combination will be further evaluated in the phase II part of the study Part B)

Multiple myeloma is an incurable disease that is characterized by the malignant proliferation of plasma cells. It is the second most common hematological malignancy, is invariable fatal. The primary approach for treatment of multiple myeloma is systemic chemotherapy. Conventional chemotherapy with melphalan and prednisone (MP) has increased the survival from 12-17 months to approximately 3 years. But several other studies have shown that combination therapy with addition of other agents such as cyclophosphamide, nitroureas or anthracyclins does not improve the prognosis of patients with multiple myeloma. During the past few years it has been demonstrated that high dose chemotherapy followed by autologous stem cell transplantation can prolong the overall survival of myeloma patients and therefore became the standard of care for younger patients. Since it has been demonstrated that high dose chemotherapy is also well tolerated by the elderly high dose chemotherapy is recommended for patients up to an age of about 70 if there is no relevant comorbidity. Thus, the development of more effective regimens for the teatment of relapsed or refractory myeloma patients is urgently needed. Treatment with corticosteroids alone can induce responses in both primarily resistant and relapsed patients with myeloma. High pulse dexamethasone (40mg daily d1-4, 9-12 and 17-21) showed response rates of 27% in primarily unresponsive patients and 21% in relapsed patients, which were initially responsive. In combination with anthracyclins like in the VAD-regimen (vincristin, adriamycin, dexamethasone)response rates of about 31% were achieved in primary unresponsive patients whereas the response rate was 65% in patients who relapsed, but had previously responded to therapy. Thus, the combination of dexamethasone with anthracyclines and vincristin achieve a certain anti-myeloma activity in relapsed or refractory patients. Nevertheless due to the neurotoxicity, treatment with vincristin of elderly patients is critical and limited. Therefore substitution of vincristine by a less toxic agent with high anti-myeloma activity like the new thalidomide analogues (see below) could reduce toxicity and improve the therapeutic efficacy of anthracycline and dexamethasone containing regimens. Protocol DSMM VII Page 7/52 29.09.2004 Version 1.1 dexamethasone containing regimens. One interesting drug with substantial anti-myeloma activity in patients with relapsed or refractory myeloma is thalidomide. Thalidomide has been demonstrated to induce remissions in about one third of relapsed myeloma patients if given as a single agent therapy. Response rates evaluated in phase-II studies could be improved up to 55% if thalidomide was administered in combination with other drugs such as glucocorticoids. However substantial side effects were observed such as somnolence, constipation and neuropathy. These observations led to development of derivatives of thalidomide in order to reduce toxicity and to improve efficacy. The thalidomide analogues represent a new class of active drugs based on immunmodulatory and direct anti-myeloma effects which have been demonstrated to have a greater potency to inhibit growth of MM and angiogenesis in vitro and in vivo than thalidomide. In a phase I study heavily pretreated patients with relapsed or refractory myeloma were treated with CC-5013 (RevlimidTM, lenalidomide). Revlimid at doses up to 25 mg/day was safe and well tolerated. The dose-limiting toxicity (DLT) was myelosupression at a dose level of 50 mg/day. In contrast to thalidomide treatment with CC- 5013 showed no significant side effects like somnolence, constipation or neuropathy. In addition 29 % of the subjects achieved a \> 50% paraprotein reduction, 71% a reduction of \> 25%. Preliminary phase II data showed in about 20 % of relapsed myeloma patients a \> 50% reduction of paraprotein, a \> 25% reduction could be observed in about 50%. No additional toxicity was observed in combination with dexamethasone. Thus, Revlimid as a single agent is well tolerated and has a profound anti-myeloma activity in patients with refractory or relapsed disease. These data suggest that Revlimid combined with chemotherapy could lead to enhanced anti-myeloma effects with acceptable toxicities. The present study will investigate the safety and the efficacy of intermittent dosing of CC-5013 (Revlimid) combined with Dexamethasone and Doxorubicin in the treatment of relapsed or refractory myeloma. Objectives Primary Objectives

Evaluation of Lenalidomide, Doxorubicin and Dexamethasone (RAD) in Patients With Relapsed or Refractory Multiple Myeloma

A Multicenter Phase I/II Trial Evaluating the Safety and Efficacy of Lenalidomide (Revlimid, CC-5013) in Combination With Doxorubicin and Dexamethasone (RAD) in Patients With Relapsed or Refractory Multiple Myeloma

University of Wuerzburg

Cyclophosphamide is used for lymphodepletion

Jie Jin, MD

Haitao Meng, MD

This study is designed to determine the safety, tolerability and engraftment potential of anti-BCMA lentivirus-transduced autologous T cells in patients with refractory or relapsed multiple myeloma.

Primary objectives:

1. Determine the safety and tolerability of CAR-BCMA T cells (autologous T cells transduced with chimeric antigen receptors recognizing BCMA) in patients with refractory or relapsed multiple myeloma.
2. Observe the cytokinetics of CAR-BCMA T cells.

Secondary objectives:

1. Observe the anti-tumor response of CAR-BCMA T cells to refractory or relapsed multiple myeloma (evaluated by diagnostic criteria International Myeloma Working Group (IMWG2014 version) as CR, sCR, ICR, MCR or VGPR).
2. Make an evaluation on the distribution and in vivo survival of CAR-BCMA T cells in peripheral blood, lymph node, and bone marrow.
3. Observe the immunogenicity of CAR-BCMA T cells, and determine if there is anti-BCMA scFv cellular immune response and anti-BCMA scFv humoral immune response.
4. Observe the change of T cell subsets relative to CAR-BCMA T。 (Tcm, central memory T lymphocytes; Tem, effector memory T lymphocytes; Treg, regulatory T lymphocytes).

Clinical Study of CAR-BCMA T in Patients With Refractory or Relapsed Multiple Myeloma

Number of DNA copies of CAR-BCMA T cells in lymph node samples or bone marrow samples at regular intervals from 24 hours after the initial infusion.

Positive incidence of anti-BCMA anti-drug antibody (ADA).

Change of T cell subsets from baseline counts after infusion(Tcm, central memory T lymphocytes; Tem, effector memory T lymphocytes; Treg, regulatory T lymphocytes).

Incidence of study related adverse events which are defined as laboratory toxicities and clinical events that are possible, likely or definitely related to study treatment at any time from the infusion until week 24, including infusion related toxicity and any toxicity possibly related to CAR-BCMA T cells.

Duration of in vivo survival of CAR-BCMA T cells is defined as "engraftment". After 24 hours of infusion, the CAR-BCMA DNA sequence was detected by PCR according to the follow-up time point, until the result of any two consecutive tests was negative and recorded as the "engraftment endpoint" of CAR-BCMA T cells.

Statistical parameter：Progression-free Survival (PFS)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
LCAR-B38M Cells in Treating Relapsed/Refractory (R/R) Multiple Myeloma	NCT03090659	Refractory or R...	LCAR-B38M CAR-T...	18 Years - 80 Years	Nanjing Legend Biotech Co.
Clinical Study of CAR-BCMA T Cells in Patients With Refractory or Relapsed Multiple Myeloma	NCT03380039	Refractory or R...	CAR-BCMA T cell... Fludarabine Cyclophosphamid...	18 Years - 70 Years	Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
A Study of the Safety and Efficacy of CNTO 328 and Bortezomib to Bortezomib Alone in Patients With Relapsed or Refractory Multiple Myeloma	NCT00401843	Multiple Myelom...	Siltuximab Bortezomib Placebo Dexamethasone	18 Years - 99 Years	Janssen Research & Development, LLC
A Study of the Safety and Efficacy of CNTO 328 and Bortezomib to Bortezomib Alone in Patients With Relapsed or Refractory Multiple Myeloma	NCT00401843	Multiple Myelom...	Siltuximab Bortezomib Placebo Dexamethasone	18 Years - 99 Years	Janssen Research & Development, LLC
Evaluation of Lenalidomide, Doxorubicin and Dexamethasone (RAD) in Patients With Relapsed or Refractory Multiple Myeloma	NCT00306813	Relapse Refractory Mult...	Revlimid	18 Years -	University of Wuerzburg
Clinical Study of CAR-BCMA T in Patients With Refractory or Relapsed Multiple Myeloma	NCT03716856	Refractory or R...	CAR-BCMA T cell... Fludarabine Cyclophosphamid...	18 Years - 70 Years	First Affiliated Hospital of Zhejiang University
Clinical Study of CAR-BCMA T Cells in Patients With Refractory or Relapsed Multiple Myeloma	NCT03380039	Refractory or R...	CAR-BCMA T cell... Fludarabine Cyclophosphamid...	18 Years - 70 Years	Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Clinical Study of CAR-BCMA T Cells in Patients With Refractory or Relapsed Multiple Myeloma	NCT03380039	Refractory or R...	CAR-BCMA T cell... Fludarabine Cyclophosphamid...	18 Years - 70 Years	Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Spots Global Cancer Trial Database for refractory or relapsed multiple myeloma