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

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

All Drugs and Chemicals

Dexamethasone

Lenalidomide

Bortezomib

Daratumumab

Dexamethasone acetate

BB 1101

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

All participants will receive 1800 mg in 15 ml Daratumumab by subcutaneous injection weekly and be given 20 mg of Dexamethasone orally once a week for 2 months. Patients who receive a partial response or better will continue on this arm.

Participants who have less than a partial response to Arm A may have Lenalidomide added to their treatment. Lenalidomide will be given orally on days 1-21 of each 28 day treatment cycle.

Participants who have less than a partial response to Arm A may have Bortezomib added to their treatment. Bortezomib will be given weekly in subcutaneous injections at a starting dose of 1/3 mg/m\^2 Days 1,8 and 15 of each 28 day treatment cycle.

Patient will receive daratumumab (1800 mg in 15 ml) administered by manual subcutaneous injections weekly for the first 8 weeks, every other week for the next 16 weeks and every 4 weeks after.

Daratumumab Injection

The dexamethasone starting dose will be 20 mg PO once a week. Commercial dexamethasone will be used. Dexamethasone is often supplied in 4 mg tablets. Accordingly, patients will take 5 (4 mg tablets) one day of the week prior to the administration of daratumumab if this corresponds to a daratumumab dosing days. In non daratumumab dosing days, dexamethasone will be taken by the patient at home, usually in the morning with breakfast.

Dexamethasone Oral

Lenalidomide will be given orally on days 1-21 of a 28 days cycle. The starting dose of lenalidomide will be based on the patient creatinine clearance per the package insert.

Specifically patients with a creatinine clearance ≥ 50 ml/min will receive 25 mg of lenalidomide PO Days 1-21. Patients with a creatinine clearance ≥ 30 but less than 50 ml/min will receive 10 mg of lenalidomide.

Patients with a creatinine clearance \< 30 ml/min are not eligible but patients who experience a deterioration in the renal function during screening or treatment may continue on lenalidomide therapy as long as the risk / benefit profile is deemed acceptable, that study therapy is in the best interest of the patient and after discussion with the study principal investigator / sponsor.

Lenalidomide Pill

Bortezomib will be given weekly subcutaneously in an effort to decrease the toxicity of the therapy. Specifically patients will receive a starting dose of bortezomib of 1.3 mg/m\^2 Days 1,8,15 of a 28 day cycle. Bortezomib will be administered in the cancer center per standard of care procedures.

Bortezomib Injection

Rachid C Baz, MD

This is a Phase II study of daratumumab based therapies for older adults with multiple myeloma.

In this response adapted approach, older adults with newly diagnosed symptomatic multiple myeloma will receive daratumumab and dexamethasone for 2 months. Patients who achieve a partial response or better will continue on daratumumab. Patients who achieve less than a partial response will have lenalidomide or bortezomib added to their therapy. Patients who experience progressive disease on daratumumab after the initial 2 months of monotherapy or on the combination of daratumumab and either lenalidomide or bortezomib will come off study

Daratumumab Based Response Adapted Therapy for Older Adults With Newly Diagnosed Multiple Myeloma

Phase II Study of Daratumumab Based Response Adapted Therapy for Older Adults With Newly Diagnosed Multiple Myeloma

The number of participants who continue on Daratumumab and Dexamethasone after 2 cycles

The number of patients who are without minimal residual disease (MRD) using Next Generation Sequencing (NGS) will be estimated and the 95% confidence interval will be computed by the Clopper-Pearson method.

Overall Response Rate (partial response or better) of the response adapted strategy using the uniform response criteria of the International Myeloma Working Group (IMWG).

Progression Free Survival (PFS) from start of treatment to death of any cause, disease progression or relapse of the date of last follow-up, whichever comes first. he PFS will be estimated by the Kaplan-Meier method and 95% confidence interval (CI) will be computed by complementary log-log transformation. The 1 and 2 year PFS and 95% Confidence Intervals will be reported.

Overall Survival (OS) from start of treatment to death of any cause or the date of last follow-up, whichever comes first. OS will be estimated by the Kaplan-Meier method and 95% confidence interval will be computed by complementary log-log transformation. The 2 year OS and 95% CI will be reported.

Janssen Scientific Affairs, LLC

H. Lee Moffitt Cancer Center and Research Institute

The main study consists of 4 phases a) 28-day screening phase; b) an induction phase inclusive of two 42-day induction treatment cycles: Isatuximab (IV), Bortezomib (SQ). Lenalidomide (PO), Dexamethasone; c) Followed by stem cell mobilization (at the discretion of the Principal Investigator \[PI\]);d) Participants will proceed with either autologous stem cell transplant or two additional induction cycles.

- Induction will be followed by a maintenance phase that continues until disease progression.

Via IV at predetermined dosage and predetermined days during each cycle

Isatuximab

Oral, predetermined dosage and predetermined days during each cycle

SQ Oral, predetermined dosage and predetermined days during each cycle

IV or Oral predetermined dosage and predetermined days during each cycle

Jacob C Laubach, MD

This research is testing whether the investigational drug isatuximab is safe and effective when used in combination with standard agents for the treatment of newly diagnosed multiple myeloma.

This is a multi-center, single-arm, open-label, Phase 2 study in patients with newly diagnosed multiple myeloma (NDMM) eligible for high dose therapy (HDT) and autologous stem cell transplant (ASCT).

In this research study, investigators are evaluating whether isatuximab is safe and effective in participants with newly diagnosed multiple myeloma when given in combination with lenalidomide, bortezomib, and dexamethsone.

* This research study involves administration of a four-drug chemotherapy regimen that combines the Investigational drug isatuximab with a standard chemotherapy regimen comprised of lenalidomide, bortezomib, and dexamethasone.
* This 4-drug regimen is not considered standard of the treatment of newly diagnosed multiple myeloma.

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug or combination of drugs to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.

The U.S. Food and Drug Administration (FDA) has approved lenalidomide, bortezomib, and dexamethasone as treatment options for this disease but the combination of these agents with isatuximab hasn't been approved.

Isatuximab, Lenalidomide, Bortezomib, and Dexamethasone in NDMM

Phase 2, Multi-Center, Single-Arm, Open-Label Study to Evaluate the Efficacy and Safety of the Combination Regimen Isatuximab, Lenalidomide, Bortezomib, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

proportion of patients who have achieved sCR, according to IMWG criteria, by the end of two cycles of induction treatment. Response will be evaluated using a Simon optimal two-stage design.

Progression-free probabilities over time will be estimated using the Kaplan-Meier method (Kaplan, 1958), presenting an estimate of median time to progression (TTP) with 95% confidence intervals (CIs). Time to progression is defined as time from registration to progression, censored at date last known to be progression-free for those who have not progressed and censored at time of death for those who died.

- Progression-free survival (PFS) will be analyzed similarly to time to progression: Progression-free probabilities over time will be estimated using the Kaplan-Meier method (Kaplan, 1958), presenting an estimate of median Time to progression (TTP) with 95% confidence intervals (CIs Time from registration to disease progression or death from any cause, censored at date last known to be progression-free for those who have not progressed or died

Duration of Response will be analyzed similarly to time to progression: Progression-free probabilities over time will be estimated using the Kaplan-Meier method (Kaplan, 1958), presenting an estimate of median time to progression (TTP) with 95% confidence intervals (CIs Time from first response after treatment to the date of disease progression or death from any cause, or date last known progression-free and alive for those who have not progressed or died.

Overall Survival will be analyzed similarly to time to progression: Progression-free probabilities over time will be estimated using the Kaplan-Meier method (Kaplan, 1958), presenting an estimate of median time to progression (TTP) with 95% confidence intervals (CIs

Overall survival: time from registration to death from any cause or date last known alive for those who have not died

Common Terminology Criteria for Adverse Events (CTCAE) of the National Cancer Institute (NCI) v5.0

Sanofi

Jacob Laubach, MD

Sponsor Investigator

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Lymphatic Diseases

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Lymphosarcoma

Antirheumatic Agents

Rituximab

Antineoplastic Agents, Immunological

to test whether adding rituximab in CD20 positive patients will have improvement in remission rate. (this arm terminated in October 2020) to add bortezomib in high risk patients at Induction to improve remission rate.

Bortezomib: patients with BM relapsed, add for 4 doses on D1,4,7, 11 in induction; dosage 1.3 mg/m2/dose as per parenteral;

Add rituximab in patients with CD20 positive ALL, rituximab: 6 doses of on D8,11of induction, D1,15 of consolidation1 and 2 with dosage 375 mg/m2 as parenteral (Terminated in Oct 2020)

rituximab injection

Chi Kong LI, Professor

Relapsed acute lymphoblastic leukaemia (ALL) has a poorer outcome than newly diagnosed ALL patients with only about 40% overall survival after re-treatment. The study CCCG Relapsed ALL 2017 study will adopt the UK R3 study stratification and treatment backbone with two new agents added. There will be a 4-week induction, followed by two consolidation courses. High-risk patients will receive allogeneic stem cell transplant. While intermediate and standard risk groups will continue maintenance treatment for another 2 years or one year. New agents will be added aiming at improving survival outcome.

1. Study of adding anti-CD20 antibody (rituximab) with chemotherapy: CD20 is found to be expressed in 40-50% of B-lineage ALL, and rituximab has been studied in adult ALL with superior survival (75% vs 47%,). There is little experience of using rituximab in pediatric ALL thus a CCCG Relapsed ALL 2017 Study will perform the study assessing the remission rate and MRD response of CD20+ ALL treated with rituximab. Six doses of rituximab and will be monitored the week 5 MRD and relapse rate as study outcome.

   (This arm was terminated in October 2020 after interim analysis showing lack of efficacy)
2. Adding bortezomid during the induction: The very early or early bone marrow relapse has low remission rate. Previous case studies showed that Bortezomib, a proteasome inhibitor, may achieve remission in refractory ALL, 80% remission in B-ALL with combination of chemotherapy and bortezomib. Thus adding bortezomib, may improve the remission rate, thus bridging to allogeneic stem cell transplant. Adding bortezomib in the relapsed chemotherapy protocol may increase the toxicity and even treatment related mortality. In this protocol, we suggested to add during the induction therapy.

Acute Lymphoblastic Leukemia (ALL) is now having over 80% event-free survival after frontline chemotherapy treatment. There is still 15-20% of patients having a relapse after initial control. Relapsed ALL is associated with lower second remission rate and also high chance of further relapse. Currently there are only a few large scale studies targeting this challenging disease. BFM Relapsed ALL studies have been organized since 1990s and have identified several important prognostic factors, including timing and site of relapse and also immunophenotyping. COG has performed several studies on relapsed ALL (AALL02P2, AALL0433, ADVL04P2) but the results are rather fragmented. Recently UK group conducted a nationwide randomized study, ALL R3 study, testing the type of anthracycline and prognostic value of minimal residual disease after induction therapy.

T-ALL relapse is having poor prognosis except for the late isolated extramedullary relapse. Long-term survival of T-ALL bone marrow relapse treated with chemotherapy is less than 10%, thus allogeneic stem cell transplant is always indicated. Whereas B-ALL has been better studied and the risk stratification of relapsed ALL is better defined.

According to previous studies, patients can be stratified into Standard, Intermediate and High-Risk groups based on site of relapse, time of relapse from first diagnosis and immunophenotyping. Early bone marrow relapse at less than 18-36 months from diagnosis is having the worst prognosis and is classified as HR. Those with late relapse at \>36 months from diagnosis is in general having a better prognosis. Bone marrow relapse is having a poorer outcome as compared to isolated extramedullary relapse (IEM). Somehow combined marrow and extramedullary relapse appear to have a better prognosis than isolated bone marrow relapse. Early B-ALL marrow relapse was only having 15-30% long-term survival, and early B-ALL IEM around 30-50% survival.

Late B-ALL marrow relapse has a higher second remission rate of around 95% and also better long term survival of 50-60%. Late B-ALL IEM is having a better prognosis of up to 70-80% survival. Based on the above criteria, several study groups including BFM, UK and COG also adopted similar strategies of stratifying patients and delivered risk-adapted treatment, with some minor variation among these groups.

Prospective and Non-randomized controlled trial

CCCG Relapsed Acute Lymphoblastic Leukemia 2017 Study in Children

Chinese Children Cancer Group Relapsed Acute Lymphoblastic Leukemia 2017 Study

bone marrow blast count \< 5% and MRD \<0.01%

survive without relapse or death or second cancer, with or without HSCT

Shanghai Children's Medical Center

Chinese University of Hong Kong

Professor

Alternating cycles of:

Selinexor oral 40mg once weekly Lenalidomide oral 25mg d 1-21 Dexamethasone 20mg d 1+2, 8+9 and 15+16 i 28 days cycles and Selinexor oral 80mg once weekly Bortezomib sc 1.3mg/sqm once weekly Dexamethasone 20mg d 1+2, 8+9 and 15+16 in 28 days cycles for up to 16 cycles (8 of each, alternating) followed by continuos selinexor 40mg(once weekly)-lenalidomide-dexamethasone

for up to 16 cycles followed by continuos lenalidomide-dexamethasone

Comparing an alternating regimen of selinexor-lenalidomide/bortezomib-dexamethasone to standard bortezomib-lenalidomide-dexamethasone

Selinexor 20 MG Oral Tablet

Lenalidomide capsule

Ida B Kristensen, MB

Hanne Norseth, MD

An unrandomized phase 2 study of selinexor in combination with lenalidomide/ bortezomib and dexamethasone to newly diagnosed, transplant in-eligible symptomatic multiple myeloma patients in a multicenter international set-up within the Nordic Multiple Myeloma Study Group

An unrandomized phase 2 study evaluating selinexor in combination with lenalidomide/ bortezomib and dexamethasone to newly diagnosed transplant in-eligible symptomatic multiple myeloma patients in a multicenter international set-up with in the Nordic Multiple Myeloma Study Group.

The study will include 50 patients, recruited within the NMSG collaborating countries. After induction patient will be treated with continued lenalidomide-dexamethasone according to SWOG, with continuous 40mg selinexor weekly in the selinexor arm (experimental arm B).

Selinexor With Alternating Bortezomib or Lenalidomide Plus Dexamethasone in TIE Newly Diagnosed MM Patients

Selinexor With Alternating Bortezomib or Lenalidomide Plus Dexamethasone in Transplant Ineligible Newly Diagnosed Multiple Myeloma Patients (SABLe): An Investigator Sponsored Trial

ORR at end of induction, with response defined according to IMWG response criteria

MRD negativity by NGS at end of induction

Time to at least PR from start of treatment

Comparison of toxicity rates according to NCI-CTCAE v4.03

Time to at least VGPR from start of treatment

Karyopharm Therapeutics Inc

Odense Patient Data Explorative Network

Ida Bruun Kristensen

Subcutaneous self administration of bortezomib

Jason Tay, MD

Amy Abel

This study is to see if the standard of care subcutaneous injection of bortezomib can safely be administered at home by the patient or caregiver. All tests and assessments are based on standard of care procedures.

Chemotherapy for malignancies is predominantly prescribed and delivered in a tertiary hospital and/or cancer centre setting. However, with modern chemotherapy, with a reduced side effect profile, this paradigm should be challenged. Indeed, the use of methotrexate and other biologics (a form of chemotherapy) in the Rheumatologic setting is commonly delivered effectively and safely in the community.

Taken together, a hospital-based model of chemotherapy delivery may not be warranted in all circumstances. Moreover, the use of this current model invariably discounts the time commitments, needs of patients and caregivers, as well as while not addressing the emerging concerns regarding system capacity, efficiency and effectiveness of safe chemotherapy delivery.

A Multicentre, Non-Blinded Study Exploring Self-Administration of Chemotherapy in the Home Environment

Number of eligible patients availing of self-administration

Myeloma outcomes as per International Myeloma Foundation Response (IMWG) Criteria

Adverse event documentation as per CTCAE version 5.0 scales of greater than grade 3

Patient Satisfaction Surveys - FACIT-TS-PS (Functional Assessment of Chronic Illness Therapy)

Patient Satisfaction Surveys - CQOLC (Caregiver Quality of Life - Cancer)

Patient Satisfaction Surveys - EORTC QLQ-MY20 (European Organization of Research and Treatment of Cancer - Quality of Life)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Daratumumab Based Response Adapted Therapy for Older Adults With Newly Diagnosed Multiple Myeloma	NCT04151667	Multiple Myelom...	Daratumumab Inj... Dexamethasone O... Lenalidomide Pi... Bortezomib Inje...	65 Years -	H. Lee Moffitt Cancer Center and Research Institute
Isatuximab, Lenalidomide, Bortezomib, and Dexamethasone in NDMM	NCT04653246	Multiple Myelom... Newly Diagnosed... Autologous Stem...	Isatuximab Lenalidomide Bortezomib Inje... Dexamethasone	75 Years -	Dana-Farber Cancer Institute
CCCG Relapsed Acute Lymphoblastic Leukemia 2017 Study in Children	NCT04224571	Acute Lymphobla...	Bortezomib Inje... rituximab injec...	3 Months - 21 Years	Chinese University of Hong Kong
Isatuximab, Lenalidomide, Bortezomib, and Dexamethasone in NDMM	NCT04653246	Multiple Myelom... Newly Diagnosed... Autologous Stem...	Isatuximab Lenalidomide Bortezomib Inje... Dexamethasone	75 Years -	Dana-Farber Cancer Institute
Selinexor With Alternating Bortezomib or Lenalidomide Plus Dexamethasone in TIE Newly Diagnosed MM Patients	NCT04717700	Multiple Myelom...	Selinexor 20 MG... Bortezomib Inje... Lenalidomide ca... Dexamethasone O...	18 Years -	Odense University Hospital
A Multicentre, Non-Blinded Study Exploring Self-Administration of Chemotherapy in the Home Environment	NCT04268199	Myeloma Myeloma Multipl...	Bortezomib Inje...	18 Years -	AHS Cancer Control Alberta
Daratumumab Based Response Adapted Therapy for Older Adults With Newly Diagnosed Multiple Myeloma	NCT04151667	Multiple Myelom...	Daratumumab Inj... Dexamethasone O... Lenalidomide Pi... Bortezomib Inje...	65 Years -	H. Lee Moffitt Cancer Center and Research Institute
Daratumumab Based Response Adapted Therapy for Older Adults With Newly Diagnosed Multiple Myeloma	NCT04151667	Multiple Myelom...	Daratumumab Inj... Dexamethasone O... Lenalidomide Pi... Bortezomib Inje...	65 Years -	H. Lee Moffitt Cancer Center and Research Institute

Spots Global Cancer Trial Database for bortezomib injection