Sikander Ailawadhi, M.D.

The purpose of this study is to characterize the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of CFT7455 administered orally in subjects with Relapsed/Refractory (r/r) Non-Hodgkin's Lymphoma (NHL) or Multiple Myeloma (MM) administered once a day (QD) as a single agent and in combination with dexamethasone.

The purpose of this study is to evaluate the safety and tolerability of APG-2575 as well as dose escalation and dose expansion stages.

The purpose of this study is to assess the pharmacokinetics (PK), safety, and tolerability of belantamab mafodotin monotherapy in participants with Relapsed/Refractory Multiple Myeloma (RRMM) who have had at least 3 lines of prior treatment and have either normal or impaired renal functions.

Belantamab mafodotin (GSK2857916) is an antibody-drug conjugate (ADC) containing humanized anti- B-cell maturation antigen (BCMA) monoclonal antibody (mAb). Renal impairment is a major complication of multiple myeloma (MM) and majority of MM participants either are at risk or already have renal dysfunction at initial diagnosis.

The purpose of this study is to assess the safety and tolerability, identify dose-limiting toxicities (DLT) and the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of APG-2575, alone or in combination with other therapeutic agents (ibrutinib or rituximab), in patients with Waldenström Macroglobulinemia (WM).

The purpose of this study is to evaluate the safety and tolerability, identify dose-limiting toxicities (DLT) and the maximum tolerated dose (MTD and recommended phase II dose (RP2D of APG2575 in combination with Pomalidomide/dexamethasone (Pd) in patients with relapsed/refractory (R/R) multiple myeloma (MM), or immunoglobulin light chain (AL) amyloidosis, and to evaluate the safety and tolerability, identify dose-limiting toxicities (DLT) and the maximum tolerated dose (MTD and recommended phase II dose (RP2D of APG2575 in combination with Daratumumab/Lenalidomide/dexamethasone (DRd) in patients with relapsed/refractory (R/R) multiple myeloma (MM).

The purpose of this study is to demonstrate the efficacy non-inferiority between isatuximab SC and isatuximab IV in combination with pomalidomide and dexamethasone (Pd), and to demonstrate the pharmacokinetic (PK) non-inferiority between isatuximab SC and isatuximab IV in combination with Pd. 

This study evaluates CLR 131 in patients with select B-cell malignancies (multiple myeloma( MM), indolent chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), and diffuse large B-cell lymphoma (DLBCL) who have been previously treated with standard therapy for their underlying malignancy.

The purpose of this study is to assess the safety and tolerability, identify dose-limiting toxicities (DLT) and determine the maximum tolerated dose (MTD) / recommended phase 2 dose (RP2D) of APG-2575.

The purpose of this study is to evaluate the safety and effectiveness of nonconforming idecabtagene vicleucel (ide-cel) in subjects with multiple myeloma per the approved prescribing information. 

Here we propose an "integrative sequencing approach" utilizing a 1500 gene exome comparative analysis between multiple myeloma or related plasma cell malignancies and normal cells coupled to capture transcriptome sequencing to provide a nearly comprehensive landscape of the genetic alterations for the purpose of identifying informative and/or actionable mutations in patients with multiple myeloma and plasma cell malignancies. The approach will enable the detection of point mutations, insertions/deletions, gene fusions and rearrangements, amplifications/deletions, and outlier expressed genes among other classes of alterations.

This is a prospective study for the long-term follow-up (LTFU) of safety and efficacy for all pediatric and adult subjects exposed to Gene-modified (GM) T cell therapy participating in a previous Celgene sponsored or Celgene alliance partner sponsored study. Subjects who received at least one GM T cell infusion, will be asked to roll-over to this LTFU protocol upon either premature discontinuation from, or completion of the prior parent treatment protocol.

The primary goal of this study is to determine response rates (>=PR) of prospectively treated MM patients with one cycle of therapy containing a combination of an immunomodulator and dexamethasone.

The purpose of this study is to estimate the rate of sustained MRD negativity (MRD negative status at any point, with a repeated MRD negative status one year later) in subjects with high-risk multiple myeloma.

The purpose of this study is to evaluate the challenges, behavioral patterns, and preferences of minority patient participation in clinical trials. Also, to develop and validate a personalized clinical trial educational platform to boost participation among underserved cancer patients.

The purpose of this study is to characterize the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of CFT7455 administered orally in subjects with Relapsed/Refractory (r/r) Non-Hodgkin's Lymphoma (NHL) or Multiple Myeloma (MM) administered once a day (QD) as a single agent and in combination with dexamethasone.

The purpose of this study for the Safety Run-in Cohorts is to evaluate the safety and tolerability of magrolimab in combination with other anticancer therapies and to determine the recommended Phase 2 dose (RP2D) of magrolimab in participants with relapsed/refractory multiple myeloma (MM) for the following combinations: magrolimab + daratumumab, magrolimab + pomalidomide + dexamethasone, and magrolimab + bortezomib + dexamethasone. Additionally, the objective of this study for the Dose Expansion Cohorts is to evaluate the effectiveness of magrolimab in combination with other anticancer therapies in participants with relapsed/refractory multiple myeloma as determined by objective response rate (ORR).

The purpose of this study is to assess the effiectiveness, safety, pharmacokinetics, pharmacodynamics, and immunogenicity of cevostamab, a humanized, full-length IgG1 T-cell-dependent bispecific (TDB) antibody, in participants with multiple myeloma (MM).

The purpose of the ALLO-605-201 study is to assess the safety, effectiveness, and cell kinetics of ALLO605 in adults with relapsed or refractory multiple myeloma after a lymphodepletion regimen comprising fludarabine, cyclophosphamide, and ALLO-647.

Here we propose an "integrative sequencing approach" utilizing a 1500 gene exome comparative analysis between multiple myeloma or related plasma cell malignancies and normal cells coupled to capture transcriptome sequencing to provide a nearly comprehensive landscape of the genetic alterations for the purpose of identifying informative and/or actionable mutations in patients with multiple myeloma and plasma cell malignancies. The approach will enable the detection of point mutations, insertions/deletions, gene fusions and rearrangements, amplifications/deletions, and outlier expressed genes among other classes of alterations.

The purpose of this study is to evaluate the effects of ibrutinib and rituximab with or without venetoclax in treating patients with previously untreated Waldenstrom's macroglobulinemia/lymphoplasmacytic lymphoma. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Rituximab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Venetoclax may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving venetoclax with ibrutinib and rituximab with may work better in treating patients with previously untreated Waldenstrom's macroglobulinemia than ibrutinib and rituximab alone.

Prior clinical experience with CD38-targeting antibodies, including daratumumab, establish this molecule as an important therapeutic target in multiple myeloma. CD38 is a type II transmembrane glycoprotein with both ectoenzymatic and signal transductionfunctions. CD38 dimerization is required for its catalytic activity (Desphande et al, 2017).Dimeric CD38 possesses both ADP ribosyl cyclase and cADPR hydrolyase activities; the former generates cyclic ADP ribose (cADPR) from NAD+ and the latter generates ADPR. CD38-mediated cADPR generation enables calcium release from intracellular stores, leading to a variety of cell type-specific physiological outcomes (Schuber and und, 2004; Lee and Aarhus, 1991). A distinct mode of CD38-dependent signal transduction involved in the regulation of proliferation and survival requires interactions with other cell surface molecules (Deshpande et al, 2017; Deaglio et al, 2007; Konopleva et al, 1998). In B- lymphocytes for example, CD38-dependent signal transduction activity utilizes interactions with CD19 and CD31/PECAM-1, the latter of which is the sole identified ligand for CD38 (Deaglio et al, 2007). Importantly, AMG 424 binding to CD38 on target cells results in redirection of T cell mediated cytotoxicity but should not modulate CD38 enzymatic activity or CD38-dependent signal transduction, based on expected serum concentrations in our proposed dosing scheme and significanty reduced binding affinity compared to a monoclonal antibody that does inhibit CD38 activity (Deckert et al., 2014).For this first-in-human study, relapsed/refractory multiple myeloma has been chosen as the indication for clinical investigation of AMG 424 because of the nearly uniform high expression of CD38 on plasma cells observed at the protein level, using flow cytometry (Lin et al, 2004). Although low level CD38 expression is widespread in different tissue types, including hematopoietic cells, plasma cells express CD38 protein at signficantly higher levels than other cell types (Malavasi et al, 2008 and Section 3 of AMG 424 IB).

The purpose of this study is to assess the maximum tolerated dose (MTD) of administering metformin in combination with nelfinavir in patients with relapsed/refractory multiple myeloma.
 

The purpose of this study is to evaluate the clinical benefit of subcutaneous (SC) daratumumab administered in combination with standard multiple myeloma (MM) regimens in participants with MM as measured by overall response rate (ORR) or very good partial response (VGPR) or better rate.

The purpose of this study is to evaluate the safety and tolerability of AMG 397 by estimating the maximum tolerated doses (MTDs) and/or biologically active doses.

This is a phase 1, multi-center, single-arm, open-label study evaluating the safety, tolerability, and anti-myeloma activity of ACTR087 (an autologous T cell product) in combination with SEA-BCMA (a monoclonal antibody) in subjects with relapsed or refractory Multiple Myeloma.

The purpose of this study is to determine the maximum-tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of ION251 in patients with relapsed/refractory multiple myeloma.

The purpose of this study is to assess the safety, pharmacokinetics and tolerability, describe the dose-limiting toxicities (DLTs), and determine the maximum tolerated dose (MTD) or maximum administered dose (MAD [in the absence of establishing the MTD]) for single agent MEDI2228 in adult subjects with multiple myeloma who are either transplant ineligible or post autologous stem cell transplant and are relapsed/refractory.

The purpose of this study is to determine (during the escalation portion) if AMG 701 given as weekly short term IV infusions is safe and tolerable followed by a dose expansion part to gain further efficacy and safety experience with AMG 701 in adult subjects with relapsed / refractory multiple myeloma.

The purpose of this study is to evaluate the safety and tolerability of AO-176, including dose-limiting toxicities (DLT), maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) when administered as monotherapy, and in combination with dexamethasone (AO-176+DEX) in adult patients with Relapsed/Refractory Multiple Myleoma (R/R MM).

Study PT-112-102, a multicenter, open-label dose-finding and pharmacokinetic study of PT-112 in patients with relapsed or refractory multiple myeloma. This is designed as a two-part study. In the first part of the study, cohorts of three patients (expanded to six patients in the event of a dose-limiting toxicity) will receive escalating doses of PT-112 until the MTD is reached, based on tolerability observed during the first 28 days of treatment. In the second part of the study, an expansion cohort of 14 patients will be treated at the recommended dose to confirm the tolerability of treatment and evaluate evidence of treatment efficacy.

The purpose of this trial is to identify the RP2D of STI-6129 by assessing the safety, preliminary effectiveness and pharmacokinetics in treating subjects with relapsed/refractory multiple myeloma (RRMM).

The purpose of this study is to evaluate the safety and tolerability of APG-2575 as well as dose escalation and dose expansion stages.

This multicenter, open-label, Phase I study will evaluate the safety, efficacy, and pharmacokinetics of atezolizumab alone or in combination with daratumumab and/or various immunomodulatory agents in participants with MM who have relapsed or who have undergone autologous stem cell transplantation (ASCT). The planned duration of this study is approximately 36 months. Cycle length will be 21 days in Cohorts A to C and 28 days in Cohorts D to F.

For cohort 1: The primary goal is to the determine the overall response rate after 6 cycles of treatment with daratumumab in combination with ibrutinib in patients who are on/or are previously treated with ibrutinib.
For Cohort 2: The primary goal is to determine the overall response rate after 6 cycles of treatment with daratumumab in combination with ibrutinib in patients who are naive to ibrutinib treatment.

Secondary Goals:
For Cohort 1
-Determine the best overall response rate to treatment with daratumumab plus ibrutinib at any time during the course of the therapy.
-The overall incidence of MRD (minimal residual disease ) negative state and the time to achieving MRD negativity at any time during this therapy.
-Progression free survival (as determined by the IWCLL criteria) among all patients.
-The overall toxicity profile of daratumumab/ibrutinib treatment in this group of patients.

For Cohort 2
-Determine the best overall response rate to treatment with daratumumab plus ibrutinib at any time during the course of the therapy.
-The overall incidence of MRD (minimal residual disease ) negative state and the time to achieving MRD negativity at any time during this therapy.
-The overall toxicity profile of daratumumab/ibrutinib treatment in this group of patients.

The purpose of this study is to determine the safety and effectiveness of bb2121 (Ide-Cel) combinations in subjects with relapsed/refractory multiple myeloma. It also aims to evaluate different agents and their doses/schedules to improve clinical effectiveness in combination with bb2121.

The purpose of this study is to compare the effectiveness and safety of bb2121 versus standard regimens in subjects with relapsed and refractory multiple myeloma (RRMM).

The purpose of the InformCLL Registry is to characterize and describe treatment patterns for those initiating treatment with approved oral kinase inhibitors, BCL-2 inhibitors and other approved anti-CLL /SLL therapies/regimens. This study also evaluates association of treatment patterns with patient characteristics, healthcare resource utilization and patient reported Health related Quality of Life (HRQoL).

The purpose of this study is to follow subjects who were treated with ACTR after the completion of the final scheduled visit in the parent clinical study or other investigational setting, such as compassionate use, named patient Investigational New Drug application, expanded access program, or equivalent setting.  These subjects will be followed for safety monitoring on a schedule of decreasing frequency through 15 years post-ACTR treatment, in accordance with US FDA Regulatory guidance pertaining to long-term safety follow-up for study subjects receiving recombinant DNA-containing investigational products.

To determine the percentage of patients achieving MRD negativity by MPF after autologous stem cell transplant (SCT) (at Day 100) using pre-SCT daratumumab consolidation.

The purpose of this study is to determine the overall response rate (ORR) of utilizing elotuzumab, pomalidomide and dexamethasone in patients with multiple myeloma resistant to daratumumab.

The purpose of this study is to document the participants characteristics, disease burden, and clinical management of participants in the United States who are treated for relapsed multiple myeloma in routine medical practice with a treatment strategies that include a proteasome inhibitor (PI) and/or immunomodulatory drug (IMiD) used either as monotherapy or combination therapy with other treatments.

This is a Phase Ib, open-label, multicenter, global study designed to assess the safety and tolerability of RO6870810 as monotherapy and in combination with daratumumab in participants with relapsed/refractory multiple myeloma. Each treatment cycle will be 21 days in length. There are two parts to this study. A dose-escalation phase (Part I) will be used to evaluate the safety and tolerability and dose limiting toxicities, and to establish the maximum tolerated dose/optimum biological dose of RO6870810 when given as monotherapy or in combination with daratumumab. A dose-expansion phase (Part II) will further characterize the safety, tolerability and activity of RO6870810 as monotherapy or in combination with daratumumab at the defined expansion dose-levels.

The primary objective of the study is to determine the safety and tolerability of I-131-CLR1404, with and without concurrent weekly dexamethasone, in patients with relapsed or refractory multiple myeloma who have previously been treated with, or are intolerant of, an immunomodulator and a proteasome inhibitor.

This phase II trial studies how well pembrolizumab, lenalidomide, and dexamethasone work in treating patients with newly diagnosed multiple myeloma that are eligible for stem cell transplant. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as lenalidomide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving pembrolizumab, lenalidomide, and dexamethasone may work better in treating patients with multiple myeloma.

The purpose of this study is to assess the side effects and best dose of R-(-)-gossypol acetic acid when given together with lenalidomide and dexamethasone, and to see how well it works in treating patients with multiple myeloma that has come back after a period of improvement or has gotten worse after treatment.

This phase I/II trial studies the best dose and side effects of ibrutinib when given together with lenalidomide and dexamethasone and how well they work in treating patients with multiple myeloma that are not eligible for transplant. Ibrutinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as lenalidomide and dexamethasone, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ibrutinib, lenalidomide, and dexamethasone may work better in treating patients with multiple myeloma.

This research is being done to find out if altering the immune system by giving Prevnar vaccine, Tadalafil, and activated marrow infiltrating lymphocytes (MILs) can improve outcomes for multiple myeloma patients who receive a standard autologous stem cell transplant.

RATIONALE: Lenalidomide and bortezomib may stop the growth of multiple myeloma by blocking blood flow to the tumor. Also, bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as elotuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as lenalidomide and dexamethasone also work in different ways to kill tumor cells or stop them from growing. Giving elotuzumab together with chemotherapy may be a better way to block cancer growth.

PURPOSE: This phase I/II trial is studying the side effects and best dose of elotuzumab and to see how well it works when given with lenalidomide, bortezomib, and dexamethasone in treating patients with multiple myeloma.

The purpose of this single-dose escalation study is to evaluate the safety and effectiveness of CAR2 Anti-CD38 A2 CAR-T Cells in patients with Relapsed or Refractory Multiple Myeloma.