Phase 1b/2 Study of Carfilzomib in Relapsed Solid Tumors, Multiple Myeloma, or Lymphoma

Study Overview
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Brief Summary
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The primary objectives of this Phase 1b/2 study were as follows: Phase 1b (Bolus and Infusion): To evaluate the safety and tolerability of carfilzomib in patients with relapsed solid tumors and in patients with relapsed and/or refractory multiple myeloma and in patients with refractory lymphoma. Phase 2 (Bolus): To evaluate the overall response rate (ORR) after 4 cycles of carfilzomib in patients with relapsed solid tumors.

Official Title
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Phase 1b/2, Multicenter Open-label Study of the Safety and Activity of Carfilzomib in Subjects With Relapsed Solid Tumors, Multiple Myeloma or Lymphoma

Conditions
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Ovarian Cancer, Renal Cancer, Non-small Cell Lung Cancer, Small Cell Lung Cancer, Solid Tumors, Multiple Myeloma, Lymphoma

Intervention / Treatment
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* Drug: Carfilzomib
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Disease related Phase 1 Subjects (Bolus and Infusion): Solid Tumor: Histologically confirmed advanced solid tumor 1 to 3 prior treatment regimens At least one site of radiographically measurable disease of ≥ 2 cm in the largest dimension by traditional computed tomography (CT) scanning technique or ≥ 1 cm in the largest dimension by spiral CT scanning (per Response Evaluation Criteria in Solid Tumors [RECIST] criteria); or if, in the Principal Investigator's opinion, evaluable disease can be reliably and consistently followed, the subject may be eligible upon approval by the Medical Monitor Multiple Myeloma (MM): Relapsed and/or refractory multiple myeloma following 2 or more prior treatment regimens. Measurable disease as indicated by one or more of the following: Serum M-protein ≥ 1 g/dL Urine M-protein ≥ 200 mg/24 hr Serum Free Light Chain: Involved free light chain (FLC) level ≥ 10 mg/dL provided serum FLC ratio is abnormal Lymphoma: Histologically or cytologically confirmed lymphoma. Patients must have had an initial diagnosis of indolent non-Hodgkin lymphoma (NHL) (including follicular, small lymphocytic, lymphoplasmacytoid, and marginal zone lymphoma), indolent disease that transformed to a more aggressive subtype, as previously described or patients may have mantle cell lymphoma. Patients are required to have received prior rituximab (alone or combined with other treatment) and are considered refractory to (defined as no response, or progression within 6 months of completing therapy) or intolerant of continued rituximab. Patients may have received up to a maximum of four prior unique chemotherapy regimens, including if not contra-indicated autologous stem-cell transplantation (ASCT). For patients to enroll in the expanded dose group for lymphoma, patients must have measurable disease Phase 2 Bolus Subjects: -Histologically confirmed advanced solid tumor diagnosis and: Non-small cell lung cancer (NSCLC): Failed at least 1 prior platinum-based chemotherapy regimen but not more than 3 prior therapies for metastatic disease Small cell lung cancer (SCLC): Failed 1 to 3 prior chemotherapy regimens Ovarian: Failed at least 1 prior platinum-based chemotherapy regimen but not more than 4 therapies for metastatic disease Renal: Failed at least 2 prior chemotherapy regimens for metastatic disease Other solid tumor types: Failed at least 1 prior chemotherapy regimen for metastatic or relapsed disease and for which standard of care therapy is no longer effective or does not exist At least one site of radiographically measurable disease of ≥ 2 cm in the largest dimension by traditional CT scanning technique or ≥ 1 cm in the largest dimension by spiral CT scanning (per RECIST criteria); or if, in the Principal Investigator's opinion, evaluable disease can be reliably and consistently followed, the subject may be eligible upon approval by the Medical Monitor Demographic Males and females ≥ 18 years of age Life expectancy of more than 3 months Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 Laboratory Adequate hepatic function, with bilirubin 1.5 times the upper limit of normal (ULN), and alanine aminotransferase (ALT) 3 times ULN Absolute neutrophil count (ANC) > 1000/mm³, hemoglobin ≥ 8 gm/dL for solid tumors or 7.0 gm/dL for MM, and platelet count ≥ 100,000/mm³ for solid tumors or ≥ 30,000/mm³ for MM. Subjects should not have received platelet transfusions for at least 1 week prior to screening Screening ANC should be independent of granulocyte- and granulocyte/macrophage colony stimulating factor (G-CSF and GM-CSF) support for at least 1 week and of pegylated G-CSF for ≥ 2 weeks Subjects may receive red blood cell (RBC) transfusions or receive supportive care with erythropoietin or darbepoetin in accordance with institutional guidelines Calculated or measured creatinine clearance (CrCl) of ≥ 20 mL/minute calculated using the formula of Cockcroft and Gault. Subjects with calculated CrCl < 20 mL/min may be allowed, only with prior approval by the Medical Monitor. Ethical/Other Written informed consent in accordance with federal, local, and institutional guidelines Female subjects of childbearing potential must have a negative serum or urine pregnancy test within 3 days of the first dose and agree to use dual methods of contraception during the study and for 3 months following the last dose of study drug. Post-menopausal females (> 45 years old and without menses for > 1 year) and surgically sterilized females are exempt from these requirements. Male subjects must use an effective barrier method of contraception during the study and for 3 months following the last dose if sexually active with a female of childbearing potential. Exclusion Criteria: Disease Related Chemotherapy with approved or investigational anticancer therapeutics, including steroid therapy, within 3 weeks prior to first dose or 6 weeks for antibody therapy Radiation therapy or immunotherapy within 3 weeks prior to first dose (except for antibody therapy, where 6 weeks is required); localized radiation therapy within 1 week prior to first dose Subjects with prior brain metastases are permitted, but must have completed treatment and have no evidence of active central nervous system (CNS) disease for at least 4 weeks prior to first dose For lymphoma patients; patients with prior stem cell transplant therapy (autologous SCT within the prior 8 weeks; allogeneic SCT within the prior 16 weeks). Patients with prior allogeneic SCT should not have evidence of moderate-to-severe graft-versus-host disease (GVHD) Evidence of CNS lymphoma Participation in an investigational therapeutic study within 3 weeks prior to first dose Prior treatment with carfilzomib Concurrent Conditions Major surgery within 3 weeks prior to first dose Congestive heart failure (New York Heart Association class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction within 3 months prior to first dose Acute active infection requiring systemic antibiotics, antivirals, or antifungals within 2 weeks prior to first dose Known or suspected human immunodeficiency virus (HIV) infection or subjects who are HIV seropositive Active hepatitis A, B, or C infection Significant neuropathy (Grade 3, Grade 4, or Grade 2 with pain) at the time of the first dose Subjects with pleural effusions requiring routine thoracentesis or ascites requiring routine paracentesis Subjects at risk* in whom the required program of oral and intravenous fluid hydration is contraindicated, e.g., due to pre-existing pulmonary, cardiac, or renal impairment High risk for Tumor Lysis Syndrome. Ethical / Other Female subjects who are pregnant or lactating Any clinically significant psychiatric or medical condition that in the opinion of the Investigator could interfere with protocol adherence or a subject's ability to give informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1B Solid Tumors: Carfilzomib 20 mg/m² Bolus<br>Participants received carfilzomib 20 mg/m² administered by bolus intravenous infusion over 2-10 minutes on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. All participants with stable disease or better after 2 cycles could continue treatment until progressive disease or unacceptable toxicity. | Drug: Carfilzomib<br>* Administered by intravenous (IV) bolus (2-10 minute) infusion or 30 minute infusion<br>* Other names: Kyprolis;|
| Experimental: Phase 1B Solid Tumors: Carfilzomib 20/27 mg/m² Bolus<br>Participants received carfilzomib 20 mg/m² administered by bolus intravenous infusion over 2-10 minutes on Cycle 1 Days 1 and 2 only, then 27 mg/m² on Days 8, 9, 15 and 16 and thereafter for the remainder of treatment. All participants with stable disease or better after 2 cycles could continue treatment until progressive disease or unacceptable toxicity. | Drug: Carfilzomib<br>* Administered by intravenous (IV) bolus (2-10 minute) infusion or 30 minute infusion<br>* Other names: Kyprolis;|
| Experimental: Phase 1B Solid Tumors: Carfilzomib 20/36 mg/m² Bolus<br>Participants received carfilzomib 20 mg/m² administered by bolus intravenous infusion over 2-10 minutes on Cycle 1 Days 1 and 2 only, then 36 mg/m² on Days 8, 9, 15 and 16 and thereafter for the remainder of treatment. All participants with stable disease or better after 2 cycles could continue treatment until progressive disease or unacceptable toxicity. | Drug: Carfilzomib<br>* Administered by intravenous (IV) bolus (2-10 minute) infusion or 30 minute infusion<br>* Other names: Kyprolis;|
| Experimental: Phase 2 Solid Tumors: Carfilzomib 20/36 mg/m² Bolus<br>Participants received carfilzomib 20 mg/m² administered by bolus intravenous infusion over 2-10 minutes on Cycle 1 Days 1 and 2 only, then 36 mg/m² on Days 8, 9, 15 and 16 and thereafter for the remainder of treatment. All participants with stable disease or better after 2 cycles could continue treatment until progressive disease or unacceptable toxicity. | Drug: Carfilzomib<br>* Administered by intravenous (IV) bolus (2-10 minute) infusion or 30 minute infusion<br>* Other names: Kyprolis;|
| Experimental: Phase 1B Solid Tumors: Carfilzomib 36 mg/m²<br>Participants received carfilzomib 36 mg/m² administered by intravenous infusion over 30 minutes on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle for at least 2 cycles. All participants with stable disease or better after 2 cycles could continue treatment until progressive disease or unacceptable toxicity. | Drug: Carfilzomib<br>* Administered by intravenous (IV) bolus (2-10 minute) infusion or 30 minute infusion<br>* Other names: Kyprolis;|
| Experimental: Phase 1B Solid Tumors: Carfilzomib 45 mg/m²<br>Participants received carfilzomib 45 mg/m² administered by intravenous infusion over 30 minutes on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle for at least 2 cycles. All participants with stable disease or better after 2 cycles could continue treatment until progressive disease or unacceptable toxicity. | Drug: Carfilzomib<br>* Administered by intravenous (IV) bolus (2-10 minute) infusion or 30 minute infusion<br>* Other names: Kyprolis;|
| Experimental: Phase 1B Solid Tumors: Carfilzomib 20/45 mg/m²<br>Participants received carfilzomib 20 mg/m² administered by intravenous infusion over 30 minutes on Cycle 1 Days 1 and 2 only, then 45 mg/m² on Days 8, 9, 15 and 16 and thereafter for the remainder of treatment. All participants with stable disease or better after 2 cycles could continue treatment until progressive disease or unacceptable toxicity. | Drug: Carfilzomib<br>* Administered by intravenous (IV) bolus (2-10 minute) infusion or 30 minute infusion<br>* Other names: Kyprolis;|
| Experimental: Phase 1B Solid Tumors: Carfilzomib 20/56 mg/m²<br>Participants received carfilzomib 20 mg/m² administered by intravenous infusion over 30 minutes on Cycle 1 Days 1 and 2 only, then 56 mg/m² on Days 8, 9, 15 and 16 and thereafter for the remainder of treatment. All participants with stable disease or better after 2 cycles could continue treatment until progressive disease or unacceptable toxicity. | Drug: Carfilzomib<br>* Administered by intravenous (IV) bolus (2-10 minute) infusion or 30 minute infusion<br>* Other names: Kyprolis;|
| Experimental: Phase 1B Solid Tumors: Carfilzomib 20/70 mg/m²<br>Participants received carfilzomib 20 mg/m² administered by intravenous infusion over 30 minutes on Cycle 1 Days 1 and 2 only, then 70 mg/m² on Days 8, 9, 15 and 16 and thereafter for the remainder of treatment. All participants with stable disease or better after 2 cycles could continue treatment until progressive disease or unacceptable toxicity. | Drug: Carfilzomib<br>* Administered by intravenous (IV) bolus (2-10 minute) infusion or 30 minute infusion<br>* Other names: Kyprolis;|
| Experimental: Phase 1b Multiple Myeloma: Carfilzomib 20/36 mg/m²<br>Participants received carfilzomib 20 mg/m² administered by intravenous infusion over 30 minutes on Cycle 1 Days 1 and 2 only, then 36 mg/m² on Days 8, 9, 15 and 16 and thereafter for the remainder of treatment. All participants with stable disease or better after 2 cycles could continue treatment until progressive disease or unacceptable toxicity. | Drug: Carfilzomib<br>* Administered by intravenous (IV) bolus (2-10 minute) infusion or 30 minute infusion<br>* Other names: Kyprolis;|
| Experimental: Phase 1b Multiple Myeloma: Carfilzomib 20/45 mg/m²<br>Participants received carfilzomib 20 mg/m² administered by intravenous infusion over 30 minutes on Cycle 1 Days 1 and 2 only, then 45 mg/m² on Days 8, 9, 15 and 16 and thereafter for the remainder of treatment. All participants with stable disease or better after 2 cycles could continue treatment until progressive disease or unacceptable toxicity. | Drug: Carfilzomib<br>* Administered by intravenous (IV) bolus (2-10 minute) infusion or 30 minute infusion<br>* Other names: Kyprolis;|
| Experimental: Phase 1b Multiple Myeloma: Carfilzomib 20/56 mg/m²<br>Participants received carfilzomib 20 mg/m² administered by intravenous infusion over 30 minutes on Cycle 1 Days 1 and 2 only, then 56 mg/m² on Days 8, 9, 15 and 16 and thereafter for the remainder of treatment. All participants with stable disease or better after 2 cycles could continue treatment until progressive disease or unacceptable toxicity. | Drug: Carfilzomib<br>* Administered by intravenous (IV) bolus (2-10 minute) infusion or 30 minute infusion<br>* Other names: Kyprolis;|
| Experimental: Phase 1b Multiple Myeloma: Carfilzomib 20/70 mg/m²<br>Participants received carfilzomib 20 mg/m² administered by intravenous infusion over 30 minutes on Cycle 1 Days 1 and 2 only, then 70 mg/m² on Days 8, 9, 15 and 16 and thereafter for the remainder of treatment. All participants with stable disease or better after 2 cycles could continue treatment until progressive disease or unacceptable toxicity. | Drug: Carfilzomib<br>* Administered by intravenous (IV) bolus (2-10 minute) infusion or 30 minute infusion<br>* Other names: Kyprolis;|
| Experimental: Phase 1b Lymphoma: Carfilzomib 20/56 mg/m²<br>Participants received carfilzomib 20 mg/m² administered by intravenous infusion over 30 minutes on Cycle 1 Days 1 and 2 only, then 56 mg/m² on Days 8, 9, 15 and 16 and thereafter for the remainder of treatment. All participants with stable disease or better after 2 cycles could continue treatment until progressive disease or unacceptable toxicity. | Drug: Carfilzomib<br>* Administered by intravenous (IV) bolus (2-10 minute) infusion or 30 minute infusion<br>* Other names: Kyprolis;|
| Experimental: Phase 1b Lymphoma: Carfilzomib 20/70 mg/m²<br>Participants received carfilzomib 20 mg/m² administered by intravenous infusion over 30 minutes on Cycle 1 Days 1 and 2 only, then 70 mg/m² on Days 8, 9, 15 and 16 and thereafter for the remainder of treatment. All participants with stable disease or better after 2 cycles could continue treatment until progressive disease or unacceptable toxicity. | Drug: Carfilzomib<br>* Administered by intravenous (IV) bolus (2-10 minute) infusion or 30 minute infusion<br>* Other names: Kyprolis;|
| Experimental: Phase 1b MM: Carfilzomib 20/45 mg/m² + Dexamethasone<br>Participants received carfilzomib 20 mg/m² administered by intravenous infusion over 30 minutes on Cycle 1 Days 1 and 2 only, then 45 mg/m² on Days 8, 9, 15 and 16 and thereafter for the remainder of treatment plus dexamethasone 40 mg weekly. All participants with stable disease or better after 2 cycles could continue treatment until progressive disease or unacceptable toxicity. | Drug: Carfilzomib<br>* Administered by intravenous (IV) bolus (2-10 minute) infusion or 30 minute infusion<br>* Other names: Kyprolis;Drug: Dexamethasone<br>* Administered orally or by IV infusion prior to carfilzomib<br>|
| Experimental: Phase 1b MM: Carfilzomib 20/56 mg/m² + Dexamethasone<br>Participants received carfilzomib 20 mg/m² administered by intravenous infusion over 30 minutes on Cycle 1 Days 1 and 2 only, then 56 mg/m² on Days 8, 9, 15 and 16 and thereafter for the remainder of treatment plus dexamethasone 40 mg weekly. All participants with stable disease or better after 2 cycles could continue treatment until progressive disease or unacceptable toxicity. | Drug: Carfilzomib<br>* Administered by intravenous (IV) bolus (2-10 minute) infusion or 30 minute infusion<br>* Other names: Kyprolis;Drug: Dexamethasone<br>* Administered orally or by IV infusion prior to carfilzomib<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1b: Number of Participants With Dose-limiting Toxicities (DLT) | Participants were evaluated for dose-limiting toxicities according to the Common Terminology Criteria for Adverse Events (CTCAE) of the National Cancer Institute (NCI) version 3.0. A DLT was defined as treatment-related ≥ Grade 2 neuropathy with pain, ≥ Grade 3 non-hematologic toxicity, Grade 4 neutropenia or thrombocytopenia lasting 7 or more days, or thrombocytopenia with bleeding. The maximum tolerated dose (MTD) for each of the 3 populations (solid tumor, multiple myeloma, and lymphoma) was defined as the dose level at which < 33% of participants experienced a dose-limiting toxicity during the first 28-day cycle. | 28 days | 
| Phase 2: Percentage of Participants With an Overall Response After 4 Treatment Cycles | Overall response is defined as participants with a best overall response of complete response (CR), partial response (PR) or stable disease (SD) after 4 cycles, assessed by the Investigator using tumor measurement and according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: Disappearance of all target and non-target lesions and no new lesions; PR: Disappearance of all target lesions, persistence of one or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits and no lesions, or, at least a 30% decrease in the size of target lesions and no progression of existing non-target lesions or any new lesions. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest size since the treatment started, and no progression of existing non-target lesions or any new lesions. | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With an Overall Response Throughout the Study | Solid tumor participants were evaluated for disease response according to RECIST, Version 1.1. Multiple myeloma participants were evaluated using the International Myeloma Working Group (IMWG) Uniform Response Criteria with the addition of minimal response (MR) based on the European Group for Blood and Marrow Transplant Group (EBMT). Non-Hodgkin lymphoma (NHL) participants were evaluated using the International Workshop NHL criteria. Waldenström macroglobulinemia (WM) participants were evaluated using Criteria from the Sixth International Workshop for WM. Overall response is defined in Outcome Measure 2 for participants with solid tumors. For NHL, overall response is defined as a best overall response of CR or PR. For multiple myeloma and WM, overall response is defined as participants with a best overall response of stringent complete response (sCR), CR, very good partial response (VGPR) or PR. | Tumor assessments occurred at the end of Cycle 2, 4, 6, 9, and 12 and continued every 3 cycles thereafter up to 6 months after last dose. Analysis includes data up to the data cut-off date of 07 October 2014; maximum duration of treatment was 35 months. | 
| Duration of Response | Duration of response is defined as the time from first evidence of a partial response or better (the first observation of PR before confirmation) to disease progression, with deaths owing to causes other than progression censored. | Tumor assessments occurred at the end of Cycle 2, 4, 6, 9, and 12 and continued every 3 cycles thereafter up to 6 months after last dose. Analysis includes data up to the data cut-off date of 07 October 2014; maximum duration of treatment was 35 months. | 
| Progression-Free Survival | Progression-free survival (PFS) is the time from start of treatment to disease progression or death (due to any cause), whichever occurred first. | Tumor assessments occurred at the end of Cycle 2, 4, 6, 9, and 12 and continued every 3 cycles thereafter up to 6 months after last dose. Analysis includes data up to the data cut-off date of 07 October 2014; maximum duration of treatment was 35 months. | 
| Time to Progression | Time to Progression (TTP) is defined as number of months between start of treatment and first evidence/documentation of disease progression. | Tumor assessments occurred at the end of Cycle 2, 4, 6, 9, and 12 and continued every 3 cycles thereafter up to 6 months after last dose. Analysis includes data up to the data cut-off date of 07 October 2014; maximum duration of treatment was 35 months. | 
| Maximum Observed Plasma Concentration of Carfilzomib | Plasma concentrations of carfilzomib were determined by a validated liquid chromatography tandem mass spectrometry method. Concentration values that were below the lower limit of quantification of 0.1 ng/mL were set to zero. Treatment groups receiving the same dose (e.g. 20 mg/m²) were combined for Day 1 analyses. | Cycle 1, Day 1, predose and at 5 minutes and 15 minutes post start of infusion (for 30-minute infusion groups only), and at the end of infusion, 5, 15, and 30 minutes; and 1, 2, and 4 hours after the end of the infusion. | 
| Time to Maximum Observed Plasma Concentration (Tmax) of Carfilzomib |  | Cycle 1, Day 1, predose and at 5 minutes and 15 minutes post start of infusion (for 30-minute infusion groups only), and at the end of infusion, 5, 15, and 30 minutes; and 1, 2, and 4 hours after the end of the infusion. | 
| Area Under the Plasma Concentration-time Curve From Time Zero to the Last Concentration Measured (AUC0-last) for Carfilzomib |  | Cycle 1, Day 1, predose and at 5 minutes and 15 minutes post start of infusion (for 30-minute infusion groups only), and at the end of infusion, 5, 15, and 30 minutes; and 1, 2, and 4 hours after the end of the infusion. | 
| Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) for Carfilzomib |  | Cycle 1, Day 1, predose and at 5 minutes and 15 minutes post start of infusion (for 30-minute infusion groups only), and at the end of infusion, 5, 15, and 30 minutes; and 1, 2, and 4 hours after the end of the infusion. | 
| Elimination Half-life (t½) of Carfilzomib |  | Cycle 1, Day 1, predose and at 5 minutes and 15 minutes post start of infusion (for 30-minute infusion groups only), and at the end of infusion, 5, 15, and 30 minutes; and 1, 2, and 4 hours after the end of the infusion. | 
| Clearance (CL) of Carfilzomib |  | Cycle 1, Day 1, predose and at 5 minutes and 15 minutes post start of infusion (for 30-minute infusion groups only), and at the end of infusion, 5, 15, and 30 minutes; and 1, 2, and 4 hours after the end of the infusion. | 
| Volume of Distribution at Steady State (Vss) of Carfilzomib |  | Cycle 1, Day 1, predose and at 5 minutes and 15 minutes post start of infusion (for 30-minute infusion groups only), and at the end of infusion, 5, 15, and 30 minutes; and 1, 2, and 4 hours after the end of the infusion. | 
| Mean Residence Time (MRT) Extrapolated to Infinity for Carfilzomib |  | Cycle 1, Day 1, predose and at 5 minutes and 15 minutes post start of infusion (for 30-minute infusion groups only), and at the end of infusion, 5, 15, and 30 minutes; and 1, 2, and 4 hours after the end of the infusion. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-small cell lung carcinoma, Small-cell lung carcinoma, Ovarian Cancer, Renal Cancer, Other solid tumors, multiple myeloma, lymphoma