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

Anti-Infective Agents

Ixazomib

HIV Protease Inhibitors

Protease Inhibitors

Enzyme Inhibitors

12 cycles of lenalidomide, ixazomib, daratumumab, and dexamethasone followed by lenalidomide until disease progression or unacceptable toxicity or a maximum of 2 years of maintenance therapy.

12 cycles of lenalidomide, ixazomib, dexamethasone, and daratumumab followed by lenalidomide, ixazomib, and daratumumab until disease progression or unacceptable toxicity or a maximum of 2 year maintenance therapy.

Evanthia Galanis, MD

Andrew Yee, MD

A randomized Phase II clinical trial will be conducted to assess the impact on progression free survival (PFS) with the addition of ixazomib and daratumumab to lenalidomide as a maintenance treatment following induction with lenalidomide, ixazomib, dexamethasone, and daratumumab.

Patients will be randomized to either:

Arm A: 12 cycles of lenalidomide, ixazomib, daratumumab, and dexamethasone followed by lenalidomide until disease progression or unacceptable toxicity or a maximum of 2 years of maintenance therapy.

Arm B: 12 cycles of lenalidomide, ixazomib, daratumumab and dexamethasone, followed by lenalidomide, ixazomib, and daratumumab until disease progression or unacceptable toxicity or a maximum of 2 years maintenance therapy.

Induction Phase: 28-day treatment cycle. Treatment continues until disease progression or for a maximum of 12 cycles as follows:

Cycles 1-2:

* Lenalidomide - 15 mg PO QD on Days 1-21
* Ixazomib - 4 mg PO on Days 1, 8, 15
* Daratumumab Subcutaneous - 15mL/1800mg on Days 1, 8, 15, 22
* Dexamethasone - 20 mg PO on Days 1, 2, 8, 9, 15, 16, 22, 23; For participants ≥75, dexamethasone administered on days 1, 8, 15, 22

Cycles 3-6:

* Lenalidomide - 15 mg PO QD on Days 1-21
* Ixazomib - 4 mg PO on Days 1, 8, 15
* Daratumumab Subcutaneous - 15mL/1800mg on Days 1, 15
* Dexamethasone - 20 mg PO on Days 1, 2, 8, 9, 15, 16; For participants ≥75, dexamethasone administered on days 1, 8, 15

Cycles 7-12:

* Lenalidomide - 15 mg PO QD on Days 1-21
* Ixazomib - 4 mg PO on Days 1, 8, 15
* Daratumumab Subcutaneous - 15mL/1800mg on Day 1
* Dexamethasone - 20 mg PO on Days 1, 2, 8, 9, 15, 16; For participants ≥75, dexamethasone administered on days 1, 8, 15

Maintenance Phase: 28-day treatment cycle. Treatment continues until progression or a maximum of 2 years of maintenance treatment:

Arm A

• Lenalidomide - 10 mg PO QD on Days 1-21

Arm B

* Lenalidomide - 10 mg PO QD on Days 1-21
* Ixazomib - 3 mg (or last tolerated dose from the induction phase) PO on Days 1, 8, and 15
* Daratumumab Subcutaneous - 15mL/1800mg on Day 1
* Dexamethasone - 20mg PO on Day 1; Unless patient is ≥75 then 10mg po day 1

In the maintenance phase, dexamethasone, 20 mg PO orally or IV will be administered to patients as a pre-infusion medication prior to daratumumab dosing. When dexamethasone is reduced to 20 mg/week and is given as pre-infusion medication, patients may receive low-dose methylprednisolone (≤20 mg) orally (or equivalent in accordance with local standards) for the prevention of delayed IRRs as clinically indicated.

If the investigator wishes to continue the maintenance regimen at the end of the 2 years maintenance treatment, patients may continue current maintenance as per standard of care.

Study of Lenalidomide/Ixazomib/Dexamethasone/Daratumumab in Transplant-Ineligible Patients With Newly Diagnosed MM

A Phase II Study of Lenalidomide, Ixazomib, Dexamethasone, and Daratumumab in Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma

Fat and lean mass will be measured using dual energy X-ray absorptiometry (DXA previously DEXA).

Blood samples will be collected to study DNA of normal and any potential tumor cells in blood. Further assessment of the genes, the RNA, and the proteins that are found in MM cells as well as in normal, noncancerous cells will be done.

Time interval between registration and progression or death.

Minimal residual disease (MRD) negativity in the blood and marrow will be determined using the IMWG criteria.

Evaluation of incidence and severity of adverse events by summaries of toxicity data/contingency tables.

Proportion of patients with reduction in tumor burden of a predefined amount.

Time from registration to death due to any cause.

Consists of 2 parts: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. The EQ VAS records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS can be used as a quantitative measure of health outcome that reflect the patient's own judgement.

The EORTC QLQ-MY20 module was developed as an addition to the QLQ-C30 for use specifically in MM. It has 4 domains (disease symptoms, side effects of treatment, body image, future perspectives). Scores range from 0 to 100; good HRQoL is indicated by high scores for future perspective and body image, and low scores for disease symptoms and side effects of treatment.

The EORTC QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status/QoL scale, and six single items. Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high/healthy level of functioning, a high score for the global health status/QoL represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology/problems.

All patients who have begun treatment will be included in the estimate of adherence rate to lenalidomide and the estimate of the adherence rate to ixazomib.

To describe functional status, comorbidity, psychological state, social activity, social support, chemotherapy toxicity, and nutrition using the geriatric assessment tool.

Celgene Corporation

Takeda

Alliance Foundation Trials, LLC.

A continuous therapy arm - continuation of therapy with Dara-Rd until PD

treatment free interval arm - discontinuation of therapy with Dara-Rd, which will be resumed at biochemical progression and given until PD

Patients who have been treated with 12 cycles of Daratumumab-Lenalidomide-Dexamethasone (Dara-Rd) will be randomized between Arm A (continuous therapy) and Arm B (treatment free interval)

Lenalidomide capsule

Sonja Zweegman, Prof Dr MD

Maarten Seefat, MD

In the Netherlands, the standard treatment for multiple myeloma is a combination of different medicines named daratumumab-lenalidomide-dexamethasone, abbreviated as Dara-Rd. In many patients this treatment results in suppressing the disease for a long time. The treatment is continued until it is not effective anymore and the disease progresses.

But until now it is unknown whether continuous therapy also leads to prolonging life. In addition, there are concerns about side effects, leading to a reduced quality of life, the development of severe toxicity that remains, which hampers subsequent therapy, and high costs due to prolonged treatment.

There are indications that temporarily stopping treatment is safe, leading to fewer side effects and allows recovering from toxicity or damage due to treatment. This may improve the quality of life.

FeAsiBility of a Treatment Free Interval in Newly Diagnosed MM Patients Treated With Daratumumab-lenalidomide-dexamethasone (HOVON174MM)

FeAsiBility of a Treatment Free Interval in Newly Diagnosed mUltiple myeLOma Patients Treated With DaratumUmab-Lenalidomide-DexamethaSone- the FABULOUS Study. A Nationwide Open-label Randomized Phase III Clinical Trial Comparing Daratumumab-lenalidomide-dexamethasone Continuously Versus Including a Treatment Free Interval

To compare Event-Free Survival (EFS) from the time of randomization, between arm A continuous therapy with Dara-Rd until PD versus arm B discontinuation of therapy with Dara-Rd, resuming therapy at the first signs of biochemical progression until PD

To compare Progression Free Survival (PFS) from the time of randomization, between arm A continuous therapy with Dara-Rd until PD versus arm B discontinuation of therapy with Dara-Rd, resuming therapy at the first signs of biochemical progression until PD

To compare adverse event (AE) burden between arms

To compare PROMs between arms via validated questionnaires such as Impact of Cancer version 2 Cancer Worry scale

To compare cost-effectiveness between arms

To determine the length of the treatment-free interval (TFI) in arm B

To determine time to (maximal) response after restart of Dara-Rd in arm B.

To compare time to next treatment (TTNT) between arms

To compare time from randomization to progression on second-line therapy (PFS2) between arms.

To compare Overall Survival (OS) between arms.

To compare the discontinuation rate and the reasons for discontinuation between arms.

To evaluate cumulative dose of daratumumab, lenalidomide and dexamethasone in both arms.

To compare dose reductions of daratumumab, lenalidomide and dexamethasone between arms.

To compare toxicity according to CTCAE v5 between arms

To compare Quality of Life between arms via validated questionnaires such as QLQ-C30, MY20, EQ-5D-5L

To compare relative dose intensity (RDI) of daratumumab, lenalidomide and dexamethasone between arms.

Stichting Hemato-Oncologie voor Volwassenen Nederland

Nutritional and Metabolic Diseases

Amyloidosis

Immunoglobulin Light-chain Amyloidosis

Proteostasis Deficiencies

Metabolic Diseases

AL Amyloidosis

Fibrinolytic Agents

Anticoagulants

Herbal and Botanical

Venetoclax

Bendamustine Hydrochloride

Heparin

Pomalidomide

Edetic Acid

Pentetic Acid

Calcium heparin

Antineoplastic Agents, Alkylating

Alkylating Agents

English Lavender

Cohort 1: Venetoclax 200 mg tablet, once daily for up to 2 cycles after achieving best response, for a maximum of 6 cycles (1 cycle = 28 days)

Cohort 2: Venetoclax 400 mg tablet, once daily for up to 2 cycles after achieving best response, for a maximum of 6 cycles (1 cycle = 28 days)

Cohort 3: Venetoclax 400 mg tablet, once daily and Dexamethasone 10 mg tablet once weekly, for up to 2 cycles after achieving best response, for a maximum of 6 cycles (1 cycle = 28 days)

Cohort 4: Venetoclax 400 mg tablet, once daily and Dexamethasone 20 mg tablet once weekly, for up to 2 cycles after achieving best response, for a maximum of 6 cycles (1 cycle = 28 days)

Venetoclax MTD (200 mg or 400 mg) with Dexamethasone (10 mg or 20 mg) as determined by the phase I results

Participants will receive one of the following as determined by the investigator:

Daratumumab, Pomalidomide, Bendamustine, or Ixazomib (+/- dexamethasone)

Venetoclax Oral Tablet, 200 mg

Cytogenetic analysis is intended for evaluation of relapsed/refractory AL amyloidosis using fluorescence in situ hybridization (FISH) using known translocation probes. Bone marrow aspirate (BMA) samples are collected in lavender top (Ethylenediaminetetraacetic acid (EDTA)) or green top (Sodium heparin) tubes. Specimen tubes shall be transported at room temperature to the laboratory on the same day of collection.

FISH assay

Venetoclax Oral Tablet, 400 mg

Dexamethasone Oral, 10 mg

Dexamethasone Oral, 20 mg

Daratumumab will be administered at a dose of 16 mg/kg by IV infusion once weekly for weeks 1 to 8, every 2 weeks for weeks 9 to 24, and every 4 weeks thereafter for a maximum of 6 months of therapy. If subcutaneous formulation is available, participants can also receive subcutaneous daratumumab (1800 mg in 15 ml) in the same schedule.

Bendamustine will be given at an initial dose of 100 mg/m\^2 intravenously on days 1 and 2 in each 28-day cycle.

Bendamustine

Pomalidomide will be administered at an initial dose of 2 mg per days on days 1-21 every 28 days.

Ixazomib will be administered at an initial dose of 4 mg per days on days 1, 8, and 15 every 28 days.

Venetoclax MTD with Dexamethasone

Research Nurse Navigator

Rajshekhar Chakraborty, MD

The purpose of this study is assess safety, safest dose, and effectiveness of venetoclax in combination with dexamethasone in participants with t(11;14) positive relapsed (comes back) or refractory (did not get better) light chain amyloidosis.

This study is a phase 1/2 study of venetoclax-dexamethasone combination therapy in relapsed/refractory t(11;14) systemic immunoglobulin light chain amyloidosis (AL) amyloidosis. The phase 1 is a dose escalation designed to determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of venetoclax in combination with low-dose weekly dexamethasone. There will be four candidate-dosing cohorts of venetoclax with or without dexamethasone in the Phase I dose-escalation. Dose escalation will be guided by the Bayesian optimal interval (BOIN) design with accelerated titration up to a total sample size of 15 participants.

The phase 2 portion is a randomized open-label study comparing the MTD or RP2D of venetoclax in combination with dexamethasone versus investigator's choice (daratumumab, pomalidomide, bendamustine, or ixazomib (with or without dexamethasone).

Venetoclax-Dexamethasone in Relapsed and/or Refractory t(11;14) Amyloidosis

An Open-label Phase I/II Trial of Venetoclax-Dexamethasone in Relapsed and/or Refractory t(11;14) Systemic Light-Chain Amyloidosis

The number of participants with dose limiting toxicities for each treatment dose will be used to determine the MTD. Dose limiting toxicity defined as grade 4 neutropenia lasting more than 5 days, any grade febrile neutropenia, grade 4 thrombocytopenia, grade 3 thrombocytopenia with bleeding, other therapy related non-hematologic toxicity of grade 2 or higher that requires discontinuation of therapy, clinical tumor lysis syndrome (TLS), laboratory TLS if the metabolic abnormalities are considered clinically significant by the investigator. All other grade 3 or higher adverse events (AEs) will be considered as DLTs with a few exceptions.

Hematologic ≥VGPR rate defined as proportion of participants achieving VGPR, low serum differential free light chain concentration (dFLC) partial response (PR), or a complete (CR).

VGPR is defined as the difference between involved and uninvolved free light chain (FLC) \[dFLC\] \< 40 mg/L. Low dFLC PR is defined as achieving a dFLC\<10 mg/L, low dFLC PR will be considered as a deep hematologic response and included in the ≥VGPR category). CR is defined as negative serum and urine immunofixation electrophoresis along with a serum free light chain ratio that lies within the normal range or skewed towards the non-amyloid forming light chain, as per institutional laboratory values

ORR defined as proportion of evaluable participants achieving organ response in each involved organ

PFS defined as time from the date of enrollment to hematologic progression or death, whichever is earlier

HRR defined as proportion of patients achieving partial response (PR) or better

DOHR defined as time from the date of first documentation of hematologic response to the date of first documented hematologic disease progression

Time to hematologic ≥VGPR defined as time from the first dose of study treatment to achievement of deep hematologic response (VGPR, low dFLC PR, or a CR)

TTNT defined as time from the date of enrollment to initiation of a subsequent line of therapy

MOD-PFS defined as time from the date of enrollment to one of the following events (whichever occurs first): death, clinical manifestation of cardiac/renal failure, or development of hematologic progression of disease

OS defined as the time from the date of enrollment to death from any cause

PROs defined as longitudinal score of "Physical Functioning" domain of Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Profile v2.0 The Physical Functioning domain contains four items with a 1 (unable to do) to 5 (without any difficulty) numeric rating.

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
Study of Lenalidomide/Ixazomib/Dexamethasone/Daratumumab in Transplant-Ineligible Patients With Newly Diagnosed MM	NCT04009109	Myeloma, Multip...	Lenalidomide Ixazomib Daratumumab Inj... Dexamethasone	18 Years - 75 Years	Alliance Foundation Trials, LLC.
FeAsiBility of a Treatment Free Interval in Newly Diagnosed MM Patients Treated With Daratumumab-lenalidomide-dexamethasone (HOVON174MM)	NCT06187441	Multiple Myelom...	Daratumumab Inj... Dexamethasone Lenalidomide ca...	18 Years -	Stichting Hemato-Oncologie voor Volwassenen Nederland
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
Venetoclax-Dexamethasone in Relapsed and/or Refractory t(11;14) Amyloidosis	NCT05451771	AL Amyloidosis	Venetoclax Oral... FISH assay Venetoclax Oral... Dexamethasone O... Dexamethasone O... Daratumumab Inj... Bendamustine Pomalidomide Ixazomib Venetoclax MTD ...	18 Years -	Columbia University

Spots Global Cancer Trial Database for daratumumab injection