Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Antineoplastic Agents

All Drugs and Chemicals

Melphalan

Amifostine

Three subjects determined to be eligible for study and agree to participate are assigned to receive 200 cGy of TSI-HT for 5 days. If this dose level is well tolerated in the first 3 subjects, the dose will be increased and given over 5 days. The dose will continue to be increased until the maximum toelrated dose is reached.

Escalating doses of TSI starting at 200cGy (escalating up to 400cGy unless maximum tolerated dose is determined in lower dose level) in cohort 1 over 5 days followed by high dose melphalan and cytoprotection followed by autologous hematopoietic stem cell transplant

Total Skeletal Irradiation

Gordon Phillips, MD

The purpose of this study is to improve the efficacy of the HDC regimen by adding a novel, "targeted" means administering a variation of total body irradiation (TBI) radiation i.e., total skeletal irradiation (TSI) administered by helical tomotherapy (HT) before, and in addition to the current standard of HDC, at a dose of 200 mg/m2 (HDMel200). The underlying postulate of this endeavor is that TSI-HT will provide additional cytoreduction to HDMel alone, without producing additional (serious) toxicity. We will utilize a classical Phase I study design (i.e., dose escalation) in myeloma patients undergoing AHSCT2 to define a maximum tolerated dose (MTD) and dose limiting toxicity (DLT). Finally, although comparisons to other therapies are not typical (and/or feasible) for a Phase I study, we will compare, whenever possible, both the toxicity and the antimyeloma activity of the AHSCT2 to AHSCT1.

This protocol will standardize, as much as possible the use of AHSCT2 both as a "tandem" and "salvage" procedure. Since sufficient AHSC (CD34+ cells) are routinely collected in adequate numbers for multiple AHSCTs, but recently used infrequently, it is important to work towards defining the optimal utilization of this resource.

While HDC/AHSCT is active most patients eventually relapse; obviously, those with lesser responses progress as well. Many investigators regard HDC/AHSCT as a "mature" modality a useful if fixed element in an evolving treatment paradigm that focuses on the introduction of new (non-HDC/AHSCT) agents with unique mechanisms of action. However, data from several related sources (including both the syngeneic and second \["tandem" or salvage\] AHSCT experience), suggests that the efficacy of HDC/AHSCT could be improved by obtaining better cytoreduction of the HDC component, thus prolonging survival and possibly even producing an increase in cures. However, to do so will require additional attention to the sources of relapse following HDC/AHSCT, mainly the residual myeloma in the patient, but perhaps also the inadvertent reinfusion of clonogenic myeloma cells in the AHSCT. For reasons discussed herein, this study will focus on the former.

We believe that the agents with more potent activity vs. the (multiple) myeloma cancer stem cell (MM-CSC) and/or their microenvironment are ultimately needed to increase the cure rate in myeloma. Unfortunately, preliminary data suggest current modalities used in myeloma therapy are only variably effective vs. these targets, and that newer agents with such activity are only now becoming available for clinical trials.

The use of these newer agents are most likely to augment, not supplant, current modalities, lending even more urgency to optimizing existing elements to try to improve the efficacy of HDC/AHSCT and especially to determine if activity vs. MM-CSC and/or the microenvironment of these current modalities can be augmented. Radiation seems especially attractive to re-evaluate, given new, "targeted" methods of administration such as those described herein. Impetus for this effort comes from the known radiosensitivity of clonogenic myeloma cells (a population that at least may contain MM-CSC), and especially given the ability of local radiotherapy to provide local disease control in myeloma, and especially given the ability of local radiotherapy to cure some patients with solitary plasmacytoma "proving" activity of radiotherapy vs. MM-CSC in this closely-related diagnosis.

It is important to note that improvement in current modalities may offer better clinical outcomes even if major effects vs. the MM-CSC and microenvironment interaction are not produced. We do not currently have the ability to measure such effects; this will not be part of this trial.

Total Skeletal Irradiation in Multiple Myeloma Before Second Autologous Hematopoietic Stem Cell Transplantation

Evaluation of a Method Designed to Improve Outcome of HD Chemotherapy and AHSCT for Patients With Myeloma: Total Marrow Irradiation Administered Via Helical Tomotherapy Plus High-Dose Melphalan and Amifostine Before AHSCT2

MTD of high dose therapy consisting of escalating doses of Total Skeletal Irradiation administered via Helical Tomotherapy, followed by standard high dose chemotherapy of high dose Melphalan (200mg/m2) with amifostine cytoprotection before AHSCT.

This objective will also include detailed short and long term assessment of hematopoiesis even if it is not the dose limiting toxicity.

Determine if quantity and severity of toxicities of TSI regimen are less than toxicities experienced in AHSCT1.

Compare using standard outcome parameters (ie; response rate, relapse rate, disease-free survival or progression-free survival and overall survival) to high dose chemotherapy/AHSCT1

University of Rochester

Professor of Medicine, Division of Hematology/Oncology

Lenalidomide

Participants have not experienced disease progression since initiation of initial systemic anti-myeloma therapy, are within 12 months of frontline autoHCT with

\>/=140mg/m2 of melphalan, initiated lenalidomide maintenance at least 6 months ago, and have a very good partial response (VGPR) or less at time of enrollment. Cohort 1 will be initiated after evaluation of preliminary efficacy and safety data from Cohort 2.

Participants have already received lenalidomide maintenance after a prior line of treatment, underwent a salvage autoHCT within the prior 2-6 months as consolidation therapy for relapsed disease after 2 to 3 prior therapies

Patients will receive 12 cycles of iberdomide as maintenance therapy. Cohort 1: Cycle 1-12: Iberdomide 1mg daily Days 1-21 of 28 day cycles Cohort 2: Cycles 1-12: Iberdomide 1mg daily Days 1-21 of 28 day cycles

Iberdomide

Gunjan Shaw, MD

Heather Landau, MD

Gunjan Shah, MD

Alexandra Gomez Arteaga, MD

Gunjan Shah, MD, MS

The purpose of this study is to see if iberdomide is a safe and effective maintenance therapy option for people with Multiple Myeloma (MM) who have had an Autologous Hematopoietic Stem Cell Transplant (AHCT) and have already had lenalidomide as maintenance therapy.

Patients will receive iberdomide treatment beyond 12 months if they continue to derive benefit from the treatment and will continue until progression of disease or unacceptable toxicity. Follow-up will be as per standard of care for a patient on maintenance therapy, and patients will not require additional research samples.

Study of Iberdomide in People With Multiple Myeloma Who Have Had an Autologous Hematopoietic Stem Cell Transplant (AHCT)

Phase II Multicenter Trial of Iberdomide as Maintenance Therapy for Multiple Myeloma Patients With Sub-Optimal Response After Autologous Hematopoietic Cell Transplantation or After Salvage Autologous Hematopoietic Cell Transplantation

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Estimate the 6-month complete response (CR) rate after iberdomide in Multiple Myeloma patients with suboptimal disease responses after an autoHCT and lenalidomide maintenance or autoHCT performed in patients who had progressed on lenalidomide maintenance previously.

Memorial Sloan Kettering Cancer Center

Nervous System Diseases

Symptoms and General Pathology

Nutritional and Metabolic Diseases

Muscular Atrophy

Lymphoma

Hematologic Neoplasms

Wasting Syndrome

Cachexia

Lymphosarcoma

asymmetric biphasic waveforms at 71 pulses per second frequency (Hz), 400 s pulse duration, 5:10s on:off time (50% duty cycle), and 1.5s ramp-up time. Participants will be in control of the muscle stimulator devices at all times and will be instructed to perform all sessions in the supine position. Bilateral NMES will be delivered via asymmetric, biphasic using four cutaneous parallel channels delivered simultaneously using 2"x4" or 3"x5" self-adhesive electrodes. For the active NMES group, participants will be encouraged to increase the amplitude to a level of moderate discomfort, such as that experienced during conventional exercise, but not to induce pain. At minimum, the amplitude should induce visible muscle contraction.

The amplitude of the muscle stimulators for the Sham group will be capped at 15 milliamperes so patients will only feel cutaneous sensation without achieving muscle contraction.

Active or Sham Neuromuscular electrical stimulation. US Food and Drug Administration-approved 2012

RS-4i Plus Sequential Stimulator (RS Medical, Vancouver, WA)

Lindsey J Anderson, PhD

Jose M Garcia, MD PhD

Some blood, bone marrow, and lymphatic (hematologic) cancers such as Hodgkin/Non-Hodgkin lymphomas, chronic lymphocytic leukemia, and multiple myeloma, are over-represented in Veterans due to exposures including Agent Orange and an increased percentage of patients of African American ethnicity. Hematologic transplantation (HCT) is a common treatment for these cancers, but often leads to deconditioning, fatigue, muscle atrophy, and poor quality of life, which are associated with complications such as hospitalization and infection. Despite the significance of these symptoms, there are no approved treatments to prevent/reverse these long-term effects. The cancer itself, side effects of chemotherapy, and sedentary behavior, contribute to these effects. Although exercise before and after HCT has helped reduce these effects, it is inconsistently recommended to patients and most remain sedentary through and after treatment. The investigators are testing an alternative exercise strategy, neuromuscular electrical stimulation, to maintain physical function quality of life after HCT.

Hematopoietic cell transplantation (HCT) reduces physical function and muscle mass and increases fatigue. Neuromuscular electrical stimulation (NMES), when used as a stand-alone intervention, improves muscle strength and muscle mass in non-cancer patients with chronic obstructive pulmonary disease and chronic heart failure. The use of NMES to combat disuse atrophy and functional decline may be particularly useful in the HCT setting as patients undergo intensive preparatory chemotherapy and often experience symptoms including severe fatigue that leave them inactive or isolated for extended time periods surrounding the transplant. However, its use in the setting of cancer has not been well-established. This proposal will contribute to developing strategies toward optimizing the safety and outcomes associated with HCT in Veterans with hematologic malignancies. The overall goals of this study are to assess 1) the efficacy of an NMES vs Sham intervention on HCT-induced reductions in physical function and muscle mass and worsening of patient-reported fatigue and QOL and 2) the association between physical function and prolonged recovery of patient-reported fatigue and QOL. The investigators hypothesize that 1) NMES will attenuate the acute HCT-induced negative impact on physical function, body composition, QOL, and fatigue compared to Sham intervention, and 2) baseline physical function will be a significant predictor of 6-month recovery of patient-reported fatigue and QOL. Aim 1: To determine the efficacy of NMES vs. Sham for attenuation of HCT-induced reductions in physical function, muscle mass, and patient-reported QOL and fatigue in patients undergoing autologous HCT. Patients will be randomized 1:1 (NMES:Sham) stratified by diagnosis. Physical function, body composition, QOL, and fatigue will be assessed at baseline (Pre, after admission to the Bone Marrow Transplant Unit but before initiation of preparatory chemotherapy) and 28 plus or minus 5 days after HCT (Follow-up 1; FU1). The primary outcome will be between-group difference in 6MWT change at FU1 compared to Pre (N=23/group; 46 total). Secondary outcomes include: body composition measured by dual-energy x-ray absorptiometry; previously validated questionnaires (Functional Assessment of Chronic Illness Therapy-Fatigue; Muscle and Joint Measures) to assess patient-reported fatigue, QOL, symptom burden, and functional status; standard of care clinical/laboratory data regarding co-morbidities, adverse events, hospitalizations, treatment history, functional status, and clinical course; and NMES process measures such as feasibility, acceptability, adherence in number of sessions, accurate use, duration/intensity, complications, and satisfaction. Aim 2: To determine predictive ability of baseline 6MWT on delayed recovery of physical function, QOL, and fatigue, patient-reported outcomes, physical function, and chart review will be collected 6-months after HCT (FU2). 6MWT at Pre will be used to determine significant predictors of QOL and fatigue at FU2 (N=46) as assessed by previously validated questionnaires. Clinical measures extracted from medical charts will include changes from FU1 to FU2 in standard of care clinical/laboratory data regarding co-morbidities, adverse events, hospitalizations, functional status, treatment history, disease trajectory, and survival. Aim 3 (exploratory): To investigate the acute impact of NMES vs. Sham during HCT on various aspects of physical function and patient-reported QOL for determining potential endpoints for future clinical trials. Exploratory measures of function (stair climbing power; muscle strength; sit-to-stand; handgrip strength; peak oxygen consumption) assessed at Pre and FU1 will be used to determine significant predictors of exploratory QOL measures (Multidimensional Fatigue Inventory; Short Form-36; European Organization for Research and Treatment of Cancer QOL Questionnaire) assessed at FU2.

Neuromuscular electrical stimulation (active vs sham signal)

During Informed Consent, patients will be instructed to not presume group assignment. An unblinded study coordinator will then randomize each participant to NMES:Sham on a 1:1 basis, stratifying by diagnosis. The unblinded coordinator will ensure each participant performs the appropriate NMES or Sham stimulus on each training day; stimulation will only occur in private exam rooms. NMES and Sham stimulators will be outwardly identical apart from a concealed "A" or "B" label indicating NMES or Sham device; the designation of A or B will only be known to the unblinded study coordinator, and not to the PI. The PI will administer all outcome assessments and conduct all statistical analyses; therefore the PI will remain blinded to NMES vs Sham group assignment until study completion. In the study database, group assignment will be coded as A or B, the PI will not know the coding of A or B. A document containing the coding will be kept in a different electronic location than the study folder.

Muscle Stimulation for Physical Function During Stem Cell Transplant

Neuromuscular Electrical Stimulation for Physical Function Maintenance During Hematopoietic Stem Cell Transplantation

Anderson Symptom Assessment Scale (range 0-10 where 10 is maximum fatigue)

dual energy fan-beam x-ray absorptiometry; bioelectrical impedance

Number of sessions completed out of total sessions

VA Office of Research and Development

Recurrence

Lymphoma, Non-Hodgkin

Lymphatic Diseases

Anti-Infective Agents

Micronutrients

Etoposide

Cytarabine

Etoposide phosphate

Carmustine

Iodine

Cadexomer iodine

Tositumomab I-131

Enzyme Inhibitors

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

BEAM + 131Iodine-Anti-B1 radioimmunotherapy and autologous HSCT

Dosimetric dose of 450 mg unlabeled Anti-B1 followed by 35 mg Anti-B1 which has been trace labeled with 5mCi of 131I-Anti-B1.

131Iodine-Anti-B1 Radioimmunotherapy

Carmustine (B) also known as BCNU Etoposide (E) Cytarabine (A) also known as Ara-C and cytosine arabinoside Melphalan (M) also known as alkeran

BEAM

Julie M Vose, MD

The purpose of this study is to assess the safety of 131I-anti-B1 Radioimmunotherapy when combined with high-dose BEAM or BEAC chemotherapy and hematopoietic stem cell transplantation. The study will also compare the difference in response rates and time to treatment failure between historical control patients receiving high-dose BEAM or BEAC chemotherapy with autologous hematopoietic stem cell transplant and patients receiving radioimmunotherapy and high-dose BEAM or BEAC chemotherapy with autologous hematopoietic stem cell transplant. Patients will receive escalating doses of radioimmunotherapy with anti-B1 radiolabeled with 131Iodine, high-dose carmustine, etoposide, cytarabine and Melphalan (BEAM) chemotherapy, and autologous hematopoietic stem cell transplant.

Thirty patients will be enrolled in this study. There will be two administrations of 131I-anti-B1 given to patients, the "dosimetric dose" and the "radioimmunotherapy dose". The dosimetric dose will consist of an infusion of unlabeled Anti-B1 (450 mg) immediately followed by an infusion of Anti-B1 (35 mg) which has been trace labeled with 5mCi of 131I-anti-B1. The total whole body dosimetry dose is then calculated over an approximated one-week time interval from the radioactive clearance data obtained by the Whole Body anterior and posterior gamma camera scans. Based upon dosimetric data calculations specific for each individual patient, a radioimmunotherapy dose will be given consisting of an infusion of unlabeled Anti-B1 (450 mg)immediately followed by an infusion of 35 mg Anti-B1 including a patient specific dose of 131Iodine-Anti-B1. Calculations will be made such that in a dose escation study, whole body radiation doses of 30, 45, 60, and 75cGy will result from the administration of the therapeutic activity of 131I-anti-B1. The amount of the unlabeled Anti-B1 administered is not calculated on a body surface area basis, but is given to provide an excess of Anti-B1 independent of tumor burden, splenic uptake, or other causes.

Hematopoietic Stem Cell Transplant for Recurrent Non-Hodgkin's Lymphoma

BEAM + 131Iodine-Anti-B1 Radioimmunotherapy and Autologous Hematopoietic Stem Cell Transplantation for the Treatment of Recurrent Non-Hodgkin's Lymphoma

Safety of 131I-anti-B1 radioimmunotherapy when combined with high-dose BEAM or BEAC chemotherapy \& HSCT. Calculations will be made such that in a dose escation study, whole body radiation doses of 30, 45, 60, and 75cGy will result from the administration of the therapeutic activity of 131I-anti-B1.

Difference in response rates/time to treatment failure between historical control patients receiving high-dose BEAM or BEAC chemo. with autologous HSCT and pateints receiving radioimmunotherapy and high-dose BEAM or BEAC chemo. with autologous HSCT

University of Nebraska

Lymphoma, Large B-Cell, Diffuse

Lymphoma, T-Cell

Lymphoma, B-Cell

B-cell Lymphoma

Gemcitabine

Busulfan

Cladribine

Treated with chidamide, cladribine, gemcitabine and busulfan(ChiCGB) therapy followed by autologous hematopoietic stem cell transplantation.

Treated with BCNU, etoposide, cytarabine and melphalan (BEAM) therapy followed by autologous hematopoietic stem cell transplantation.

Chidamide

6 mg/m2 intravenously once daily @ Day -7 \~ -3

3.2 mg/kg intravenously once daily @ Day -7 \~ -4

200 mg/m2 intravenously once daily @ Day -7 \~ -4

400 mg/m2 intravenously once daily @ Day -7 \~ -4

autologous hematopoietic stem cells infusion after ChiCGB or BEAM chemotherapy

Autologous hematopoietic stem cell transplant

Jie Zhou, MD

Jing Tan, MD

Jie Ji, MD

Kaiji Zhang, MD

Hai Yi, MD

Yaqiong Li, MD

Hongyun Xing, MD

Fang Xu, MD

Xingli Zou, MD

Jian Xiao, MD

Ying Yuan, MD

High-dose chemotherapy (HDT) with autologous stem cell transplantation (ASCT) plays a vital role in treating high-risked or relapsed/refractory lymphoma. Our previous study showed chidamide combined with cladribine, gemcitabine, and busulfan (ChiCGB) as conditioning therapy improved the survival of these patients. So we designed this trial to verify if ChiCGB were better than BCNU, etoposide, cytarabine, and melphalan (BEAM). Patients with diffuse large B cell or extra-nodal NK/T cell Lymphoma who consent to this study will be randomized into the trial group who receive ChiCGB or the control group whom receive BEAM. Patients will be followed for up to 2 years after the hematopoietic cell transplantation (HCT).

ChiCGB vs BEAM in High-risk or R/R Lymphomas

ChiCGB Versus BEAM With Autologous Stem-Cell Transplantation in High-risk Hodgkin and Non-Hodgkin Lymphoma - A Prospective, Multi-centered, Randomized Clinical Trial

Release after the publication of results of this trial

Progression free survival of this group of patients at the end of 2 year

Overall survival of this group of patients at the end of 2 year

non-hematologic adverse events @ Day +100

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Total Skeletal Irradiation in Multiple Myeloma Before Second Autologous Hematopoietic Stem Cell Transplantation	NCT01182233	Multiple Myelom...	Total Skeletal ...	18 Years - 70 Years	University of Rochester
Study of Iberdomide in People With Multiple Myeloma Who Have Had an Autologous Hematopoietic Stem Cell Transplant (AHCT)	NCT05354557	Multiple Myelom...	Iberdomide	18 Years - 75 Years	Memorial Sloan Kettering Cancer Center
Muscle Stimulation for Physical Function During Stem Cell Transplant	NCT04364256	Autologous Hema...	RS-4i Plus Sequ...	18 Years -	VA Office of Research and Development
Hematopoietic Stem Cell Transplant for Recurrent Non-Hodgkin's Lymphoma	NCT00574509	Lymphoma	131Iodine-Anti-... BEAM	19 Years - 70 Years	University of Nebraska
Total Skeletal Irradiation in Multiple Myeloma Before Second Autologous Hematopoietic Stem Cell Transplantation	NCT01182233	Multiple Myelom...	Total Skeletal ...	18 Years - 70 Years	University of Rochester
ChiCGB vs BEAM in High-risk or R/R Lymphomas	NCT05466318	Lymphoma, Large... Lymphoma, T-Cel...	Chidamide Cladribine Gemcitabine Busulfan Carmustine Etoposide Cytarabine Melphalan Autologous hema...	16 Years - 65 Years	Sichuan University
Study of Iberdomide in People With Multiple Myeloma Who Have Had an Autologous Hematopoietic Stem Cell Transplant (AHCT)	NCT05354557	Multiple Myelom...	Iberdomide	18 Years - 75 Years	Memorial Sloan Kettering Cancer Center

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