NCT04219202NARecruiting
University Hospital Heidelberg · University Hospital of Heidelberg, Radiation Oncology, Heidelberg
The study is a randomized, open, prospective phase II study. The aim of the study is to evaluate the safety and feasibility of a hypofractionated, accelerated radiation approach based on the incidence of grade 3-5 NCI Common Terminology Criteria for Adverse Events (NCI-CTC-AE ) toxicity and / or termination of the planned therapy for any reason with neoadjuvant radiation with active beam guidance of the retroperitoneal Sarcomas using protons or carbon ions before a subsequent tumor resection.
Eligibility: 18 Years to · All · * Histologically confirmed retroperitoneal soft-tissue sarcoma which is resectable or marginally resectable
* Karnofsky index of ≥ 70%
* Age from 18 years
* Completed patient information and written consent
* ability to give consent
NCT06452602Phase 2Recruiting
Tianjin Medical University Cancer Institute and Hospital · Tianjin Cancer Hospital, Tianjin, Tianjin Municipality
This trial is conducted in patients with unresectable locally advanced esophageal squamous cell carcinoma. The investigators plan to enroll 60 patients with unresectable locally advanced esophageal cancer in Tianjin cancer hospital.
After 2 cycles of induction immunochemotherapy, 60 patients with ESCC will be divided into 2 groups (CR+PR group and SD+PD group) according to the efficacy of induction therapy. Patients in the CR+PR group will be treated with the same immunochemotherapy regimen plus concurrent radiotherapy (50.4Gy/1.8Gy/28f) . And immunotherapy will maintain for a maximum of 1 year. Patients in the SD+PD group will be treated with concurrent chemoradiotherapy (Radiotherapy: PTV/PGTV:50.4Gy/59.92Gy/28f and another chemotherapy regimen). Immunotherapy will not used during chemoradiotherapy because of immunotherapy resistance.
The trial can effectively stratify patients by induction immunochemotherapy, and a more appropriate treatment regimen for patients has the potential to further improve PFS and prolong OS in all patients.
Eligibility: 18 Years to 75 Years · All · 1. Volunteered to participate, cooperated with follow-up visits;
2. Aged 18 years or older, both male and female;
3. Histologically confirmed cT1N2-3M0 or cT2-4bN0-3M0 or cT1-4bN0-3M1( supraclavicular lymph node metastasis) locally advanced ESCC (8th AJCC );
4. Clinically staged as II-IVb inoperable locally advanced ESCC(including non-resectable, or with contraindications to or refusal of surgery);
5. ECOG performance status 0 or 1;
6. Presence of measurable and/or non-measurable lesions as defined by RECIST 1.1;
7. Haven't received any previous systemic anti-tumor therapy (including but not limited to systemic chemotherapy, radiotherapy, molecularly targeted drug therapy, immunotherapy, biologic therapy, topical therapy and other investigational therapeutic agents);
8. Provide fresh or archived tumour tissue samples within 6 months (fresh samples preferred) for biomarker analysis (e.g.PD-L1). Sample types are formalin-fixed, paraffin-embedded \[FFPE\] tumour tissue blocks or at least 5 unstained, 3-5 μm thick FFPE tumour tissue sections;
9. Expected survival ≥ 3 months;
10. Adequate hematologic function, defined as ANC ≥1500/μl, platelet count ≥100,000/μl and hemoglobin count ≥9.0 g/dl or ≥5.6 mmol/l;
11. Adequate renal function, defined as creatinine ≤1.5× ULN or measured or calculated creatinine clearance ≥60 mL/min for those with creatinine levels \>1.5× ULN (Calculated from the Cockcroft-Gault formula);
12. Adequate hepatic function, defined as total bilirubin ≤1.5× ULN and ALT/AST/AKP levels ≤2.5× ULN and albumin ≥2.8 g/dl;
13. Adequate coagulation function, defined as INR ≤1.5× ULN and APTT≤1.5× ULN unless the patient is receiving anticoagulant therapy as long as INR is within the therapeutic range;
14. Women of childbearing potential with a negative urine pregnancy test within 3 days before the first administration of the investigational drugs.
15. Documented informed consent.
NCT06737822Phase 3Recruiting
All India Institute of Medical Sciences, Jodhpur · All India Institute of Medical Sciences, Bhubaneshwar, Bhubaneswar, Odisha
A majority of oral cancer patients in India present in the advanced stage hence tend to have poor oncological outcomes. Chemotherapy has been associated with improved oncological outcomes in various cancers but its role in oral cancer is not well defined in curative setting apart from radio sensitization. Attempted trials of neoadjuvant chemotherapy failed to show oncological advantage despite an excellent response rate, in part due to poor patient selection. Patients with a biologically aggressive disease are more likely to benefit, hence we intend to find out the oncological advantage of adding induction chemotherapy to oral squamous cell cancer with advanced nodal disease (N2-N3).
Earlier studies suffered from their heterogeneous patient population- all head and neck subsites together and included a spectrum ranging from early- stage operable cases to inoperable cancer. Due to such patient selection, the intended results were never met. The current study is intended to study the role of chemotherapy in curable patients who are most likely to benefit (biologically aggressive and advanced stage of presentation).
Objective
Primary:
To study the 2 year disease free survival by adding induction chemotherapy before surgery in patients of oral cancer with advanced nodal disease as compared to upfront surgery.
Secondary:
To assess treatment related outcomes between the treatment arms- Response rate; Treatment compliance; treatment related toxicity, postoperative complications and Quality of life.
To study the overall survival at 2 years. Oral cancer tissue biobanking for future translational research.
Study population Operable Oral cavity Squamous cell carcinoma with advanced nodal disease (N2-N3) Study Design Open label, Multi centric, randomized controlled trial with allocation ratio of 1:1
Sample Size The primary end point is disease-free survival. In order to have 80% power to detect a hazard ratio of 0.67, using a two-sided significance level, a total of 184 events are needed. Assuming an accrual rate of 15 patients a month, 300 patients need to be recruited. The analysis of DFS will take place 32 months after the start of the trial. The follow-up of patients will continue for 5 years. The analysis of OS will be conducted when 184 deaths are observed. taking 10% of withdrawal of consent, a total of 346 patients need to be included.
Inclusion Criteria Biopsy proven, operable oral Squamous cell carcinoma cT1-T4; cN2-N3, with adequate organ function, Age- 18-75 years, ECOG-PS:0-2 Treatment Arms
Standard Arm (SURG arm):
Surgery (Wide local Excision/composite resection with neck dissection) followed by adjuvant Radiotherapy ± Concurrent Chemotherapy
Experimental Arm (ICT):
2# TPF or TPX based induction chemotherapy followed by Surgery (Wide local Excision/composite resection with neck dissection) followed by adjuvant Radiotherapy ± Concurrent Chemotherapy
Study endpoints Primary- Disease free survival Secondary- Overall survival/ Quality of life/ Toxicity of treatment/ Treatment tolerance
Eligibility: 18 Years to 75 Years · All · * Newly diagnosed, treatment naïve, biopsy or cytology proven OSCC
* Clinical Stage cT1-4a, cN2-N3\*\*, M0- as per UICC 2018
* No evidence of distant metastases on chest x-ray and/or CT Thorax
* ECOG PS 0-2
* No contraindication to Cisplatin or radiotherapy\*\*\*
* Patients eligible for definitive curative intent treatment after discussion in multidisciplinary tumour board
* Adequate organ function at time of participation, defined as Haematological: Haemoglobin \> 9gm/dl, ANC ≥ 1500/cmm3, Platelet ≥100000/cmm3 Liver Function test: Bilirubin ≤2 x upper limit normal (ULN), AST/ALT/ ALP ≤ 2.5 x ULN Renal Function test: Creatinine ≤ 1.5 ULN, Creatinine Clearance ≥60 ml/min.
NCT06945718Phase IIRecruiting
Fujian Medical University · Fujian Medical University Union Hospital, Fuzhou, Fujian
Taking patients with locally advanced gastric adenocarcinoma (cT2-4a, N-/+, M0) as the research subjects, to evaluate whether the clinical efficacy of laparoscopic beyond D2 regional lymph node dissection for gastric cancer with indocyanine green tracer is better or not.
Eligibility: 18 Years to 75 Years · All · Age from 18 to 75 years Primary gastric adenocarcinoma (papillary, tubular, mucinous, signet ring cell, or poorly differentiated) confirmed pathologically by endoscopic biopsy cT2-4a, N-/+, M0 at preoperative evaluation according to the AJCC Cancer Staging Manual, 8th Edition No distant metastasis, no direct invasion of pancreas, spleen or other adjacent organs in the preoperative examinations Performance status of 0 or 1 on the ECOG (Eastern Cooperative Oncology Group) scale ASA (American Society of Anesthesiology) class I to III Written informed consent
NCT06203327Phase IIRecruiting
Shanghai Jiao Tong University School of Medicine · Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, Shanghai Municipality
Despite declining incidence rates, gastric cancer (GC) ranks the fourth leading cause of cancer-related mortality and the fifth most common cancer worldwide, with the highest incidence reported in Eastern Asia. The 5-year overall survival rate of early GC exceeds 90%, which was well above advanced GC. Most intestinal-type GCs follow the Correa cascade-inflammation,atrophy, intestinal metaplasia (IM), dysplasia and subsequent carcinoma. The presence of gastric mucosal atrophy and intestinal metaplasia are important risk factors for GC. The purpose of this study was to investigate the incidence of GC attributed to atrophic gastritis in a region with high incidence of GC.
Eligibility: 18 Years to 70 Years · All · * Ability and willingness to participate in the study and to sign and give informed consent
* Biopsies were collected based on the recommendation of updated Sydney system
NCT05880667Phase 1Recruiting
Fox Chase Cancer Center · Fox Chase Cancer Center, Philadelphia, Pennsylvania
Single arm Phase I trial of adaptive stereotactic body radiation (SBRT) for abdominopelvic metastases. Adaptive SBRT will allow for escalation of the prescription dose and target coverage while maintaining grade 3+ toxicity no greater than 10%. Subjects with metastatic cancer to the abdomen or pelvis requiring local control or palliation will be enrolled.
Eligibility: 18 Years to · All · 1. Subjects must have histologically or cytologically confirmed cancer that is metastatic (all solid tumor types accepted), with at least one target lesion untreated by radiation, IR techniques, or growing in the abdomen or pelvis. Adjacent lymph nodes in the same region (5 cm or closer) constitute one active lesion. Target lesion must be measurable according to RECIST v 1.1. Previous systemic therapies are allowed.
2. Age \> 18 years.
3. ECOG performance status 0 or 1
4. Estimated survival of \>/= 12 months
5. Subjects must have normal organ and marrow function as defined below
* Absolute neutrophil count \> 1,500/mcL
* Platelets \> 100,000/mcL
* Total bilirubin \< 2 mg/dL
* AST/ALT (SGOT/SGPT) \< 5X ULN
* Creatinine \< 1.5X ULN OR
* Creatinine clearance ≥ 50 ml/min/1.73 m2 for subjects with creatinine levels above institutional normal
6. Subjects must possess the ability to understand and willingness to sign a written informed consent and HIPAA consent document. Translation services including translation of informed consent documents will be provided, as feasible, to encourage diversity of inclusion of eligible patients.
NCT06755554Phase 3Recruiting
Ukrainian Society of Clinical Oncology · National Cancer Institute, Kyiv
The study aims to evaluate the safety and benefits of using indocyanine green in lymph node dissection for gastric cancer surgery. The primary endpoint is the average number of lymph nodes removed. Secondary study points are the average number of ICG-positive lymph nodes; the average number of metastatic ICG-positive lymph nodes; the number of postoperative complications and complications associated with the administration of ICG.
Patients who meet the inclusion criteria for this study will be enrolled in the study after reviewing and signing an informed consent form.
All patients will be included in one group and will receive surgical treatment in the amount of total or subtotal gastrectomy with lymphadenectomy D1, D1+, D2 or D2+.
ICG is injected by the patient by endoscopic submucosal injection into 4 points around the tumor 24-12 hours before the start of the surgical intervention.
Assessment of the number of fluorescent lymph nodes will be performed intraoperatively with their subsequent removal and mapping. The incidence of postoperative complications will be assessed by Clavien-Dindo.
Eligibility: 18 Years to · All · * Tumor spread: cT2-4a cN0-3,
* cM0;
* Age: 18 - 80;
* Gender: men and women;
* ECOG: 0 - 1;
* Histologic type of tumor: Adenocarcinoma of any subtype;
* Degree of differentiation: G1 - G4;
* Tumor localization: cardiac region, stomach floor, stomach body, antrum, pylorus, and pyloric region of the stomach;
* Tumor spread: absence of tumor invasion into adjacent structures;
* No history of cancer in the last 5 years;
* No previous chemotherapy, surgery or radiation treatment for another cancer (except for neoadjuvant chemotherapy for gastric cancer);
* Absence of severe comorbidity restricting laparoscopic approach.
NCT04850729Phase IIRecruiting
Nanfang Hospital, Southern Medical University · Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong
Perioperative drug treatment has gradually become the standard regimen for locally advanced gastric cancer, whereas only a subset of patients could benefit from it. Therefore, one major challenge for perioperative drug treatment is to construct promising biomarkers and to screen out potential beneficial patients. Recent evidence has revealed that tumor microenvironment (TME) is highly associated with the prognosis of gastric cancer. Meanwhile, tumor microenvironment score (TMEscore) established with transcriptomic data is a robust biomarker for predicting prognosis and guiding individualized immunotherapy strategies. However, its predictive value for perioperative drug treatment outcomes warrants further exploration and validation. The study is a multi-center, observational study to evaluate the relationship between the efficacy of perioperative treatment and tumor microenvironment in patients with locally advanced resectable gastric and gastro-oesophageal junction adenocarcinoma, aiming at further determining the predictive value of TMEscore and establishing a comprehensive treatment-efficacy evaluation system for gastric cancer.
Eligibility: 18 Years to 75 Years · All · 1. Histologically or cytologically confirmed locally advanced resectable gastric and gastro-oesophageal junction adenocarcinoma at the stage of cT2-T4aNxM0 (AJCC 8th) without distant metastases and without infiltration of adjacent structures and organs.
2. 18-75 years old.
3. Willing to provide residual tumor tissues after routine clinical diagnosis for tumor microenvironment detection analysis.
4. Patients agree to participate in the study and sign the informed consent.
5. Patients need to receive perioperative drug therapy.
6. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1.
NCT07727759Phase IIRecruiting
Minia University · Liver and GIT Hospital, Faculty of Medicine, Minia University, Minya, Minya Governorate
Removing a large part of the liver (major hepatectomy) can cure primary and secondary liver cancers, but it carries the risk of post-hepatectomy liver failure (PHLF), a serious complication in which the liver left behind - the future liver remnant (FLR) - cannot meet the body's metabolic needs. PHLF occurs after roughly 5% to 15% of major hepatectomies and is the leading cause of postoperative death.
Before surgery, surgeons routinely use CT scans to measure how much liver will remain (CT volumetry). Volume alone does not tell the whole story. After a large resection the remaining liver can rotate and shift into the empty space left behind, kinking or compressing the veins that drain it. The resulting congestion can make an apparently adequate remnant fail.
This prospective, multicenter, observational cohort study tests whether adding two elements to standard CT volumetry improves the preoperative prediction of liver failure:
1. Hepatic vascular deformation mapping (VDM), a three-dimensional image-analysis technique that quantifies the geometry and displacement of the hepatic veins and the portal vein; and
2. A set of simple, reproducible measurements that any radiologist can make on a standard CT scan (hepatic vein diameters, congestion index, spleen volume, liver attenuation, and the distances from the veins to the planned resection plane).
Consecutive adults undergoing major hepatic resection (three or more Couinaud segments) at several tertiary hepatobiliary centers will be enrolled. The preoperative CT scans already performed as part of routine care are analyzed centrally by a core imaging laboratory. There is no additional imaging, no extra hospital visit, and no study-specific intervention: every patient receives standard surgical care. Participants are followed for at least 30 days after surgery to record liver failure (International Study Group of Liver Surgery criteria, operationalized by the "50-50" rule on postoperative day 5) and radiologic evidence of hepatic congestion.
Three nested prediction models are compared - volumetry alone; volumetry plus VDM; and volumetry plus VDM plus the simple radiology parameters - and the best-performing model is converted into a practical risk score. Because the study runs across several centers, the model can be validated by leaving one center out at a time, which gives an honest estimate of how well it would perform at a new hospital. The goal is a generalizable, easy-to-use tool that tells surgeons, before the operation, which patients are genuinely at risk of post-hepatectomy liver failure.
Eligibility: 18 Years to · All · * Age 18 years or older
* Scheduled to undergo major hepatic resection, defined as the removal of three or more Couinaud segments, at a participating center
* Availability of a preoperative multiphasic contrast-enhanced CT of the liver of quality sufficient for central core-laboratory analysis
* Willing and able to complete postoperative clinical and laboratory follow-up for at least 30 days
* Written informed consent
NCT07305428NARecruiting
The University of Hong Kong · Queen Mary Hospital, Hong Kong
Hepatocellular carcinoma (HCC) is one of the commonest cancers worldwide and ranks the third on the incidence of cancer-related death. There are more than 500000 new cases diagnosed annually worldwide. The incidence and prevalence of HCC are on rising trend with the majority of the disease burden is in Asia where viral hepatitis B is endemic. Surgical resection, radiofrequency ablation (RFA) and liver transplantation (LT) represent the only chance of cure for HCC patients. Despite more aggressive surgical approach has been adopted in most Asian countries, yet curative intervention remains only amendable in 30% of patients. Most patients are diagnosed with intermediate or advanced stage diseases; the long-term cure rate is only 0-10%. Hence, every effort has been made in an attempt to convert inoperable HCC into operable disease (i.e. downstaging) in order to improve the chance of survival of these patients. The current study, to our knowledge, will be the first study in the field to deploy a novel treatment strategy to deploy both immunotherapy and stereotactic beamed radiotherapy to induce tumor shrinkage rendering it become operable cancer.
Eligibility: 18 Years to 80 Years · All · * Diagnosis of HCC is made according to American Association for the Study of Liver Diseases (AASLD) practice guideline 2010: patients with cirrhosis of any etiology and patients with chronic hepatitis B (HBV) who may not have fully developed cirrhosis, the presence of liver nodule \>1cm and demonstrated in a single contrast enhanced dynamic imaging \[either computed tomography (CT) or magnetic resonance imaging (MRI)\] of intense arterial uptake and "washout" in portal venous and delayed phases.
* Tumor size 5-25 cm or number of lesions ≤3 or segmental portal vein involvement
* Age: 18-80 years old
* Child Pugh liver function class A-B7
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
NCT07331883Phase 2Recruiting
Ruijin Hospital · Sanming First Hospital, Sanming, Fujian
Primary liver cancer-particularly hepatocellular carcinoma (HCC)-remains a major health burden in China, characterized by high incidence and mortality rates and poor 5-year survival. Spontaneous rupture of HCC (SRHCC), although a relatively uncommon complication, is associated with extremely high mortality and marked geographic variation, with disproportionately higher incidence and rupture-related deaths reported in Asian populations. For patients with preserved liver function and resectable tumors, hepatic resection can offer favorable long-term survival and even a potential cure. However, despite surgical removal, the risk of postoperative recurrence is substantially increased, and long-term outcomes remain unsatisfactory. Currently, there is no validated adjuvant therapy to reduce recurrence or improve survival after resection.
In recent years, immune checkpoint inhibitors (ICIs) in combination with anti-angiogenic agents have demonstrated synergistic antitumor activity and manageable safety in advanced HCC. Notably, studies of sintilimab plus a bevacizumab biosimilar have shown significant improvements in overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Moreover, emerging evidence in the adjuvant and perioperative settings suggests that PD-1 blockade may delay recurrence in high-risk patients, such as those with microvascular invasion.
Based on the high postoperative recurrence rate in SRHCC patients and the existing therapeutic gap, along with established evidence of the efficacy of immune checkpoint inhibitors combined with antiangiogenic therapy in advanced HCC, conducting a prospective Phase II single-arm study of adjuvant therapy with sintilimab plus the bevacizumab biosimilar holds significant clinical and scientific value. This study aims to evaluate the tolerability of this combination regimen in postoperative SRHCC patients at high risk of recurrence. It is expected to provide a more effective treatment option for patients diagnosed with spontaneously ruptured hepatocellular carcinoma, improve their prognosis, and offer scientific evidence for future treatment strategies.
Eligibility: 18 Years to 75 Years · All · * Patients voluntarily provide written informed consent, with authorization obtained from the patient or legal representative prior to any protocol-related procedures.
* Age ≥ 18 years and ≤ 75 years; both female and male
* Spontaneous tumor rupture with hemorrhage confirmed by imaging prior to or during surgery, with a postoperative pathological diagnosis of hepatocellular carcinoma (HCC).
a) For cases where tumor rupture is an incidental finding during surgery, a clinical history of abdominal pain within the two weeks preceding surgery is required.
* CNLC Stage I-II.
* Having undergone curative surgical resection, with intraoperative irrigation using ≥5000 mL of distilled water or normal saline, confirmed negative surgical margins on postoperative pathology, and achieving a complete response (CR) confirmed by imaging within 4-8 weeks after surgery.
* ECOG PS 0-1
* Child-Pugh A (score ≤6).
* Life expectancy ≥12 months
* Laboratory test results obtained within 3 days prior to the first dose must meet the following criteria:
1. Hematological:(Except for hemoglobin, the patient must not have received a blood transfusion, granulocyte colony-stimulating factor \[G-CSF\], or hematopoietic agents within 2 weeks prior to screening.) i. Absolute neutrophil count ≥1.5 × 10⁹/L; ii. Platelet count ≥75 × 10⁹/L; iii. Hemoglobin ≥90 g/L.
2. Serum biochemistry:
i. Serum albumin ≥30 g/L; ii. Total bilirubin ≤1.5 × ULN; iii. ALT and AST ≤3 × ULN; iv. Serum creatinine ≤1.5 × ULN, or creatinine clearance \>50 mL/min.
3. International normalized ratio (INR) ≤1.2 or prothrombin time (PT) ≤2 seconds above the upper limit of normal.
4. Urinalysis:Urine protein \<2+.(If urine protein is ≥2+, a 24-hour urine protein test may be performed; patients may be enrolled if 24-hour urine protein \<1.0 g.)
* For patients with HBV infection (i.e., HBsAg-positive), HBV DNA must be tested. HBV DNA levels must be \<2000 IU/mL (or \<10⁴ copies/mL if the study site reports results in copies/mL). Patients with HBV DNA ≥2000 IU/mL must receive at least 1 week of antiviral therapy prior to the first dose, using only nucleos(t)ide analogues such as entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide. HBV DNA levels must show a ≥1-log (10-fold) reduction before initiation of study treatment. All HBV-infected patients must continue antiviral therapy throughout the entire study period. Patients who are HCV RNA-positive must receive antiviral treatment according to current clinical guidelines.
* Female patients of childbearing potential must have a negative β-hCG pregnancy test prior to the first dose. Female patients of childbearing potential and male patients with partners of childbearing potential must agree to use effective contraception during treatment and for 6 months after the last dose of study medication.
NCT04661137Phase 2Recruiting
Hackensack Meridian Health · Lombardi Comprehensive Cancer Center, Washington D.C., District of Columbia
This is a prospective, 2-arm (with an additional exploratory arm), open-label, multicenter study looking at the response rate of patients receiving selinexor (KPT-330), in combination with carfilzomib, daratumumab or pomalidomide.
Multiple Myeloma patients with documented disease progression or refractory disease while on current treatment with any carfilzomib-containing regimen (arm 1), any pomalidomide-containing regimen (arm 2) or any daratumumab-containing regimen (exploratory arm) will be included in the study. Patients will be assigned to the respective groups according to their current treatment. If a subject has received more than one of the above therapies, then assignment will be made at their physician's discretion (e.g treatment decision can be made based upon patient and physician preferred tolerance.).
Patients will receive treatment until progressive disease (PD), death, toxicity that cannot be managed by standard of care, or withdrawal, whichever occurs first.
Eligibility: 18 Years to · All · 1. Age ≥18 years at time of informed consent.
2. Histologically confirmed MM and evidence of disease progression while on one of the below MM regimens:
* Arm 1: Refractory to or disease progression while on a carfilzomib-containing regimen
* Arm 2: Refractory to or disease progression while on a pomalidomide-containing regimen
* Exploratory Arm: Refractory to or disease progression while on a daratumumab-containing regimen
3. Measurable disease as defined: Serum M-protein ≥ 0.5 g/dL; urine M-protein excretion at least 200 mg/24h; serum FLC ≥ 100 mg/L, provided that FLC is abnormal; if serum protein electrophoresis is felt to be unreliable for routine M-protein measurement (i.e. IgA MM) then quantitative Ig levels by nephelometry or turbidometry are acceptable; for non-secretory disease, bone marrow plasma cells ≥ 20% or a biopsy-proven target lesion by PET/CT or MRI is acceptable
4. Documented evidence of disease progression (by IMWG criteria) or refractory disease on the current treatment as defined as:
* Achieving SD or less for ≥ 1 cycle during treatment with regimens stated in #2 (i.e. relapsed) OR
* \<25% response (i.e. never achieved MR) or PD during or within 60 days from the end-of most recent MM regimen as listed in #2 (i.e. refractory).
5. Any non-hematological toxicities (except for peripheral neuropathy) that patients experienced from treatments in previous regimens have resolved to Grade 2 or less by Cycle 1 Day 1.
6. ECOG 2 or less
7. Adequate hepatic function within 28 days prior to C1D1:
1. Total bilirubin \< 1.5 × upper limit of normal (ULN) (except patients with Gilbert's syndrome who must have a total bilirubin of \< 3 × ULN), and
2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) normal to \<2 × ULN.
8. Adequate renal function within 28 days prior to C1D1 as determined by estimated creatinine clearance of ≥ 30 mL/min, calculated using the Cockcroft and Gault formula (140 - Age) • Mass (kg)/ (72 • creatinine mg/dL); multiply by 0.85 if female (Cockcroft 1976).
9. Adequate hematopoietic function within 7 days prior to C1D1: total white blood cell (WBC) count ≥1500/mm3, absolute neutrophil count ≥1000/mm3, hemoglobin ≥8.5 g/dL and platelet count ≥75,000/mm3 (patients for whom \<50% of bone marrow nucleated cells are plasma cells) or ≥50,000/mm3 (patients for whom ≥50% of bone marrow nucleated cells are plasma cells).
1. Patients receiving hematopoietic growth factor support, including erythropoietin, darbepoetin, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), and platelet stimulators (eg, eltrombopag, romiplostim, or interleukin-11) must have a 2-week interval between growth factor support and the Screening assessments, but they may receive growth factor support during the study.
2. Patients must have:
* At least a 2-week interval from the last red blood cell (RBC) transfusion prior to the Screening hemoglobin assessment, and
* At least a 1-week interval from the last platelet transfusion prior to the Screening platelet assessment.
However, patients may receive RBC and/or platelet transfusions as clinically indicated per institutional guidelines during the study.
10. Female patients of childbearing potential must have a negative serum pregnancy test at Screening. Female patients of childbearing potential and fertile male patients who are sexually active with a female of childbearing potential must use highly effective methods of contraception throughout the study and for 3 months following the last dose of study treatment.
