Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Heart and Blood Diseases

Symptoms and General Pathology

Rare Diseases

Lymphoma

Multiple Myeloma

Neoplasms, Plasma Cell

Plasmacytoma

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphoma, Mantle-Cell

Lymphoma, B-Cell, Marginal Zone

Lymphoma, Large B-Cell, Diffuse

Lymphoproliferative Disorders

Paraproteinemias

Lymphoma, B-Cell

Hematologic Diseases

Waldenstrom Macroglobulinemia

Blood Protein Disorders

Immunoproliferative Disorders

Neoplasms by Histologic Type

Lymphatic Diseases

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Hemorrhagic Disorders

Lymphoma, Non-Hodgkin

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Lymphosarcoma

Chronic Lymphocytic Leukemia

Mantle Cell Lymphoma

B-cell Lymphoma

Marginal Zone Lymphoma

Diffuse Large B-Cell Lymphoma

Primary Central Nervous System Lymphoma

All Drugs and Chemicals

Radiopharmaceuticals

Iopofosine I 131 in Waldenstroms Macroglobulinemia

Iopofosine I 131 in Central Nervous System Lymphoma

Iopofosine I 131 in Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma, and Diffuse Large B-Cell Lymphoma

Iopofosine I 131 single dose

Iopofosine I 131 multiple dose

Iopofosine I 131 fractionated dose

Kate Oliver

Cellectar B site

Cellectar Biosciences

Jarrod Longcor

Part A of this study evaluates iopofosine I 131 (CLR 131) in patients with select B-cell malignancies (multiple myeloma( MM), indolent chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL)/Waldenstrom Macroglobulinemia (WM), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), and central nervous system lymphoma (CNSL) who have been previously treated with standard therapy for their underlying malignancy. Part B (CLOVER-WaM) is a pivotal efficacy study evaluating IV administration of iopofosine I 131 in patients with WM that have received at least two prior lines of therapy.

B-cell malignancies represent a diverse collection of diseases and, taken together, make up the majority of hematologic malignancies. B-cell lymphomas represent the largest percentage of these neoplasms, and the relapsed and/or refractory B-cell lymphomas have proven very difficult to treat. Patients that have failed prior therapy, including WM patients, represent a very challenging patient population with significantly reduced life-expectancy.

Iopofosine I 131 is a targeted radiotherapeutic that exploits the selective uptake and retention of Cellectar's proprietary phospholipid ethers (PLEs) by malignant cells. Cellectar Biosciences' novel cancer-targeted small-molecule compound is radiolabeled with the radioisotope iodine-131 (I-131) which has previously been used approved for use in select tumors. Iopofosine I 131 has been evaluated in over 80 xenograft and spontaneous (transgenic) tumor models where it was demonstrated to be effective in eliminating tumors.

Based on the critical unmet medical need for effective agents with novel mechanisms of action in B-cell malignancies, Cellectar Biosciences has chosen to expand this ongoing study to assess iopofosine I 131 in a pivotal expansion cohort in Waldenstrom's Macroglobulinemia patients that have received at least two prior lines of therapy.

Study of Iopofosine I 131 (CLR 131) in Select B-Cell Malignancies (CLOVER-1) and Pivotal Expansion in Waldenstrom Macroglobulinemia

An Open-Label, Multicenter, Phase 2 Study of Iopofosine I 131 (CLR 131) in Patients With Relapsed or Refractory (R/R) Select B-Cell Malignancies (CLOVER-1) and Expansion Cohort in Patients With Waldenstrom Macroglobulinemia (CLOVER-WaM)

Response assessment per International Uniform Response Criteria for Multiple Myeloma; Lugano Criteria for lymphoma; International Workshop on Chronic Lymphocytic Leukemia for CLL; VIth Waldenstrom's Macroglobulinemia Criteria for Response Assessment; or 2005 Response Criteria for CNS Lymphoma

Response assessment per criteria modified from VIth Waldenstrom's Macroglobulinemia Criteria for Response Assessment

Cellectar Biosciences, Inc.

Syndrome

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Anemia

Hematologic Neoplasms

Anemia, Aplastic

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Graft vs Host Disease

Hodgkin Disease

Bone Marrow Diseases

Precancerous Conditions

Myeloproliferative Disorders

Bone Marrow Failure Disorders

Pancytopenia

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Aplastic Anemia

Chronic Myeloid Leukemia

Homologous Wasting Disease

Hodgkin Lymphoma

Acute Graft Versus Host Disease

Chronic Myeloproliferative Disorders

Antineoplastic Agents

Antirheumatic Agents

Anti-Infective Agents

Tacrolimus

Cyclophosphamide

Mycophenolic Acid

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Calcineurin Inhibitors

Enzyme Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antitubercular Agents

All patients treated on this trial will have hematological malignancies that are in remission at the time of the transplant. Their diseases would be expected to relapse with standard therapy alone.

Total body irradiation is given in 8 fractions over 4 days (total dose of 12 Gy).

Total Body Irradiation (TBI)

After TBI, the patients will receive a dose of 2 x 10e8 of their donor's T cells. After this infusion, the patients will have 2 rest days.

Donor Lymphocyte Infusion (DLI)

Cyclophosphamide is administered 2 days after the DLI to help tolerize the donor T cells. It is given at a dose of 60 mg/kg/d for 2 days

Started the day before the transplant to prevent graft versus host disease (GVHD)

Mycophenolate Mofetil (MMF)

Started the day before the transplant to prevent graft-versus-host disease (GVHD)

One day after the cyclophosphamide is finished, the patients will receive a CD34 selected-donor stem cell product. This is the day of transplant.

The CliniMACS® Plus Instrument will be used for the selection of human CD34+ hematopoietic stem and progenitor cells in human allogeneic hematopoietic stem cell transplantation.

Hematopoietic stem cell transplantation (HSCT)

Dolores Grosso, DNP, CRNP

Neal Flomenberg, MD

The primary hypothesis of this research study is that patients in remission undergoing myeloablative haploidentical hematopoietic stem cell transplantation (HSCT) on the Thomas Jefferson University (TJU) 2 Step treatment regimen will have a disease-free survival (DFS) rate at 1 year that is the same or better than the historical DFS of patients with similar diagnoses and ages undergoing matched sibling HSCT. Based on a review of the literature a DFS rate of 50% or better at 1 year would meet the criterion for an effective alternative therapy. A DFS rate of 75% or better would imply superior efficacy of the TJU 2 Step approach over T-replete matched sibling HSCT.

The primary rationale for the development of this research study is to find out if the Thomas Jefferson University (TJU) 2 Step approach to stem cell transplant is an effective treatment for patients with blood cancers who require transplant for long-term survival but are without an available matched-sibling donor. Historically, survival rates for patients undergoing half-matched stem cell transplant have been much lower than those observed after matched sibling stem cell transplant. This may be due to the poor-risk disease features of the patients by the time they are referred for hematopoietic stem cell transplantation (HSCT). Survival post half-matched stem cell transplant has also been affected by the requirement to remove or soothe donor T cells resulting in higher rates of infection and relapse. Newer approaches to haploidentical HSCT, such as the TJU 2 Step approach, utilize cyclophosphamide (CY) to tolerize donor lymphocytes instead of removing them completely from the donor product. This has resulted in less infection without concomitant increase in severe graft-versus-host disease (GVHD) and has increased overall survival as compared to older haploidentical treatment approaches due to decreases in regimen-related morbidity.

Because of the historically low overall survival (OS) after haploidentical HSCT, it has become a procedure of last resort with most centers unwilling to consider it unless all other options are exhausted. With the recent development of regimens such as the TJU 2 Step approach which provide safe, alternative platforms for HSCT, it is now feasible, and ethically more acceptable, for patients without matched sibling donors to undergo HSCT prior to being heavily pretreated or developing resistant disease. In this setting, i.e. equivalent regimen safety profiles and more homogenous patient comparison groups, it is possible to more accurately compare antitumor effects between matched sibling donors and haploidentical donors. There is ample evidence in the literature that HLA mismatching causes GVHD. There is not a large body of evidence supporting the notion that HLA mismatching provides superior tumor control translating into greater relapse free survival. As compared to more common types of transplants where donor T cells are given to the recipient, the investigators would surmise that the T cell tolerization associated with the TJU 2 Step approach may decrease the anti-tumor effects of the donor immune system. Conversely, the greater degree of human leukocyte antigen (HLA) mismatch with exploitation of NK effects may mitigate some of the attenuated T cell alloreactivity.

Thus, in the context of comparable regimen-related toxicity, our major aim in this research study is to compare graft versus tumor effects as measured by disease-free survival (DFS) between matched sibling HSCT and the TJU 2 Step haploidentical HSCT. If DFS is similar despite T cell tolerization, than the TJU 2 Step haploidentical approach should be considered an effective alternative therapy for those patients in remission without a matched sibling donor. The widespread benefit of this outcome would be the enfranchisement of segments of the population who are without available matched donors resulting in a delay or a failure to receive this potentially life-saving therapy. If DFS survival after treatment on the TJU 2 Step haploidentical approach is superior to what would be expected after matched sibling HSCT, then one could conclude that haploidentical HSCT confers greater tumor control forming the basis for future studies regarding the potential benefits of utilizing haploidentical donors over matched sibling donors when both types of donors are available.

Bone Marrow Transplantation of Patients in Remission Using Partially Matched Relative Donor

A Two Step Approach to Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Hematologic Malignancies in Remission From HLA Partially-Matched Related Donors

1-year post-transplant disease free survival (DFS), defined as success if a patient is alive and disease free at 1-year post-transplant.

Probability of overall survival at 15 months post-treatment, defined as success if a patient is alive 1-year post-transplant.

Sidney Kimmel Cancer Center at Thomas Jefferson University

All patients treated on this trial will have hematological malignancies that are in remission at the time of the transplant. Their diseases would be expected to relapse with standard therapy alone.

Total Body Irradiation (TBI): Total body irradiation given in 8 fractions over 4 days (total dose of 12 Gy).

Donor Lymphocyte Infusion (DLI): After TBI, the patients will receive a dose of 2 x 10e8 of their donor's T cells. After this infusion, the patients will have 2 rest days.

Cyclophosphamide: Cyclophosphamide is administered 2 days after the DLI to help tolerize the donor T cells. It is given at a dose of 60 mg/kg/d for 2 days

Mycophenolate Mofetil (MMF): Started the day before the transplant to prevent graft versus host disease (GVHD)

Tacrolimus: Started the day before the transplant to prevent graft-versus-host disease (GVHD)

Hematopoietic stem cell transplantation (HSCT): One day after the cyclophosphamide is finished, the patients will receive a CD34 selected-do

TJU 2 Step Regimen

Age, Continuous

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

Ethnicity (NIH/OMB)

United States

Region of Enrollment

Dolores Grosso, CRNP, DNP

Disease-Free Survival (DFS)

Probability of Overall Survival at 15 Months Post-treatment

Overall Study

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Antibodies

Dexamethasone

Lenalidomide

Dexamethasone acetate

Immunoglobulins

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Angiogenesis Inhibitors

Growth Inhibitors

Carfilzomib, Lenalidomide, Dexamethasone, Belantamab Mafodotin

Phase I - Chemotherapy multiple agents systemic Phase II - Maximum Tolerated Dose from Phase I

Shebli Atrash, MD, MS

This research study is being done to learn if the study drug belantamab mafodotin, in combination with other standard medications, can improve multiple myeloma. This study will also help determine what effects, good and/or bad, this combination of study drugs have on subjects and their cancer, and to evaluate the overall response to this study treatment combination.

This is a phase I dose escalation and expansion study in RMM and RRMM followed by a single arm phase II expansion in high risk, NDMM. The phase I portion of the protocol will utilize a standard 3+3 dose escalation design to determine the maximum tolerated dose (MTD) and RP2D of the KRd-belantamab mafodotin combination. The phase II portion of the trial is a two-stage design that will assess the efficacy and safety of the combination in newly diagnosed, high-risk MM patients.

Study of Carfilzomib, Lenalidomide, Dexamethasone and Belantamab Mafodotin in Multiple Myeloma

A Phase I/II Study of Carfilzomib, Lenalidomide, Dexamethasone and the Anti-B-Cell Maturation Antigen (BCMA) Antibody Drug Conjugate Belantamab Mafodotin in Multiple Myeloma

The SAE variable will be determined for each subject as a binary variability indicating whether or not subject experienced a protocol-defined SAE.

The AE variable will be determined for each subject as a binary variability indicating whether or not subject experienced an AE per CTCAE V5.0.

The AESI variable will be determined for each subject as a binary variability indicating whether or not subject experienced a protocol-defined AESI.

Describe subject outcomes of progression free survival and overall survival for MRD concordant and discordant cases

Compare MRD status concordance between NGF and QiP mass spectrometry

Assess BCMA (B Cell Maturation Antigen) expression by plasma cells prior to therapy and at relapse using formalin-fixed paraffin embedded (FFPE) bone marrow biopsies.

Establish peripheral blood and bone marrow immunologic profiles throughout therapy.

Correlate plasma cell BCMA (B Cell Maturation Antigen) expression with Progression Free Survival (PFS) and Overall Survival (OS).

Correlate serum cell sBCMA (serum B Cell Maturation Antigen) concentration with Progression Free Survival (PFS) and Overall Survival (OS).

DLTs will be determined for each subject enrolled in Phase I as a binary variable indicating whether the subject experienced a DLT during Cycle 1 of belantamab mafodotin-containing protocol directed induction therapy.

CR will be determined for each subject as a binary variable indicating whether the achieved a best overall response to induction therapy of CR or better.

CR will be determined for each subject as a binary variable indicating whether the achieved a best overall response to induction therapy of CR or better

The best overall response will be determined as an ordered categorial variable indicating the subject's best response at any point along the treatment continuum.

will be determined for each subject as a binary variable indicating whether the achieved a best overall response to induction therapy of VGPR or better.

The best overall response will be determined as an ordered categorial variable indicating the subject's best response at any point along the treatment continuum

. Minimal residual disease (MRD) (via NGF 10-5 and 10-6) will be determined for each subject after suspected CR for Phase I subjects and at the following timepoints for Phase II subjects: after induction therapy, after ASCT, and after 12 cycles of maintenance therapy (post Cycle 18visit) and every 12 months post Cycle 18 sample.

TTFR will be calculated for all subjects achieving an sCR, CR, VGPR, or PR. This will be defined as the time from initiation of belantamab mafodotin-containing protocol directed induction therapy to the time of first disease assessment indicating either sCR, CR, VGPR or PR

Time to best response will be calculated for all subjects achieving an sCR, CR, VGPR or PR. This will be defined as the time from initiation of belantamab mafodotin-containing protocol directed induction therapy to the time of best disease assessment indicating either sCR, CR, VGPR or PR.

TTP is defined as the duration of time from enrollment to the study (treatment start date) to first occurrence of progressive disease

DoR will be calculated for each subject achieving a PR or better and will be calculated from the time of the first assessment that identified response until disease progression or death.

OS is defined as the duration from enrollment to the study (treatment start date) to the date of death from any cause.

PFS is defined as the duration of time from enrollment to the study (treatment start date) to first occurrence of either progressive disease or death (from any cause), whichever comes first.

Amgen

GlaxoSmithKline

Wake Forest University Health Sciences

Janus Kinase Inhibitors

Proteasome Inhibitors

Cohort 1) 5mg ruxolitinib, Cohort 2) 10mg ruxolitinib, Cohort 3) 15mg ruxolitinib

Cohort A) non-responders to Phase I regimen, Cohort B) responders to Phase I regimen

Carfilzomib

Ruxolitinib

Shebli Atrash, MD

The primary objective of Phase I is to establish the maximum tolerated dose (MTD) of ruxolitinib in combination with carfilzomib and dexamethasone. The primary objective of phase II is to evaluate progression-free survival (PFS) at 4 months in multiple myeloma subjects who receive the combination treatment carfilzomib, dexamethasone, and ruxolitinib.

This is an open-label, Phase I/II study of carfilzomib, ruxolitinib, and low-dose dexamethasone for carfilzomib-refractory multiple myeloma. Phase I is designed to evaluate overall maximum tolerated dose (MTD) of ruxolitinib in combination with carfilzomib and dexamethasone in the following cohorts: Cohort 1) 5mg ruxolitinib, Cohort 2) 10mg ruxolitinib, Cohort 3) 15mg ruxolitinib. Phase II is designed to evaluate 4-month progression-free survival (PFS) in the following cohorts: Cohort A) non-responders to Phase I regimen, Cohort B) responders to Phase I regimen. Up to 18 evaluable subjects will be enrolled in Phase I over approximately 12 months. An additional 30 evaluable subjects will be enrolled in Phase II over 24 months.

LCI-HEM-MYE-CRD-004 (MMRC-073 CARJAK): Study of CRD for Carfilzomib-Refractory Multiple Myeloma

LCI-HEM-MYE-CRD-004 (MMRC-073 CARJAK): Phase I/II Study of Carfilzomib, Ruxolitinib, and Low Dose Dexamethasone for Carfilzomib-Refractory Multiple Myeloma

DLTs will be determined for each subject as a binary variable indicating whether or not the subject experienced a DLT during Cycle 1

Objective response will be determined for each subject as a binary variable indicating whether or not the subject achieved a best overall response of PR or better as per the IMWG criteria

Clinical benefit will be determined for each subject as a binary variable indicating whether or not the subject achieved a best overall response of minimal response (MR) or better as determined by the IMWG criteria

Disease control will be determined for each subject as a binary variable indicating whether or not the subject achieved a disease response or stable disease for greater than or equal to 8 weeks

PFS is defined as the duration of time from the initiation of study treatment with ruxolitinib to first occurrence of either progressive disease or death without progressive disease.

Time to best response will be defined as the time from initiation of ruxolitinib treatment to the time of best objective status assessment of response.

Overall survival is defined as the duration from initiation of ruxolitinib treatment to the date of death from any cause.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Iopofosine I 131 (CLR 131) in Select B-Cell Malignancies (CLOVER-1) and Pivotal Expansion in Waldenstrom Macroglobulinemia	NCT02952508	Waldenstrom Mac... Multiple Myelom... Chronic Lymphoc... Small Lymphocyt... Lymphoplasmacyt... Marginal Zone L... Mantle Cell Lym... Diffuse Large B... Central Nervous...	Iopofosine I 13... Iopofosine I 13... Iopofosine I 13...	18 Years -	Cellectar Biosciences, Inc.
Bone Marrow Transplantation of Patients in Remission Using Partially Matched Relative Donor	NCT01350245	Acute Myeloid L... Myelodysplastic... Biphenotypic Le... Acute Lymphocyt... Chronic Myeloid... Chronic Lymphoc... Plasma Cell Neo... Lymphoma Hodgkin's Disea... Aplastic Anemia	Total Body Irra... Donor Lymphocyt... Cyclophosphamid... Mycophenolate M... Tacrolimus Hematopoietic s...	18 Years -	Thomas Jefferson University
Study of Iopofosine I 131 (CLR 131) in Select B-Cell Malignancies (CLOVER-1) and Pivotal Expansion in Waldenstrom Macroglobulinemia	NCT02952508	Waldenstrom Mac... Multiple Myelom... Chronic Lymphoc... Small Lymphocyt... Lymphoplasmacyt... Marginal Zone L... Mantle Cell Lym... Diffuse Large B... Central Nervous...	Iopofosine I 13... Iopofosine I 13... Iopofosine I 13...	18 Years -	Cellectar Biosciences, Inc.
Study of Carfilzomib, Lenalidomide, Dexamethasone and Belantamab Mafodotin in Multiple Myeloma	NCT04822337	Multiple Myelom...	Carfilzomib, Le...	18 Years -	Wake Forest University Health Sciences
LCI-HEM-MYE-CRD-004 (MMRC-073 CARJAK): Study of CRD for Carfilzomib-Refractory Multiple Myeloma	NCT03773107	Multiple Myelom...	Carfilzomib Ruxolitinib Dexamethasone	18 Years - 75 Years	Wake Forest University Health Sciences

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