Trial Title:
A Study of CyBorD (Cyclophosphamide, Bortezomib, Dexamethasone) Plus Daratumumab in People With Monoclonal Gammopathy of Renal Significance (MGRS)
NCT ID:
NCT06083922
Condition:
Multiple Myeloma
Monoclonal Gammopathy of Renal Significance
Conditions: Official terms:
Multiple Myeloma
Paraproteinemias
Monoclonal Gammopathy of Undetermined Significance
Dexamethasone
Cyclophosphamide
Bortezomib
Daratumumab
Conditions: Keywords:
Cyclophosphamide
Bortezomib
Dexamethasone
Daratumumab
22-424
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Intervention model description:
This trial will include a safety run-in-stage that will enroll patients from either
cohort, which purpose is to test the safety of the combination. The run-in-stage will be
followed by:
A Simon-two-stage phase II study that will enroll patients with cast nephropathy (cohort
A), A pilot study that will enroll patients with all other MGRS excluding AL amyloidosis
(cohort B).
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Cyclophosphamide
Description:
Days 1, 8 and 15, Cycles 1-8
Arm group label:
Arm A will include patients with cast nephropathy
Arm group label:
Arm B will include all other MGRS associated diseases with the exclusion of AL amyloidosis
Intervention type:
Drug
Intervention name:
Bortezomib
Description:
Days 1,8,15, Cycles 1-8, Days 1,15 Cycles 9+
Arm group label:
Arm A will include patients with cast nephropathy
Arm group label:
Arm B will include all other MGRS associated diseases with the exclusion of AL amyloidosis
Intervention type:
Drug
Intervention name:
Dexamethasone
Description:
Days 1,2,8, 9,15,16, 22, 23, Cycles 1-8
Arm group label:
Arm A will include patients with cast nephropathy
Arm group label:
Arm B will include all other MGRS associated diseases with the exclusion of AL amyloidosis
Intervention type:
Drug
Intervention name:
Daratumumab
Description:
Days 1,8,15,22, Cycles 1-2, Days 1,15 Cycles 3-6, Day 1 Cycles 7+
Arm group label:
Arm A will include patients with cast nephropathy
Arm group label:
Arm B will include all other MGRS associated diseases with the exclusion of AL amyloidosis
Summary:
The purpose of this study is to find out whether cyclophosphamide, bortezomib,
dexamethasone (CyBorD) with daratumumab SC is a safe treatment combination for
MGRS-associated kidney disease including cast nephropathy associated with multiple
myeloma. In addition, the researchers will find out whether the study drug combination is
an effective treatment for these conditions.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
Inclusion criteria for cast nephropathy associated with MM:
- Subjects must have a confirmed diagnosis of NDMM as per standard IMWG criteria
- Subjects must have measurable disease, defined as meeting at least 1 of the
following criteria ≤ 14 days prior to registration:
- A monoclonal Immunoglobulin (M-protein) concentration on serum protein
electrophoresis (SPEP) of ≥ 0.5 g/dL.
- Measurable urinary light chain secretion by quantitative analysis using urine
protein electrophoresis (UPEP) of ≥ 200 mg/24 hours.
- Involved serum free light chain (FLC) level ≥ 10 mg/dL, provided the serum FLC
ratio is abnormal.
- eGFR must be <40 ml/min/1.73m2
- Subjects must have histologically confirmed diagnosis of monoclonal gammopathy
associated CN by kidney biopsy OR If a kidney biopsy is not available, a percentage
of urine albumin excretion (%UAE) < 25 % AND FLC > 50 mg/dL
Inclusion criteria for other MGRS associated renal diseases
- Histologically confirmed diagnosis of MGRS-associated renal disease by kidney biopsy
- Presence of monoclonal gammopathy by serum protein electrophoresis, Immunofixation,
or Free Light Chain Assay
- Evidence of plasma cell dyscrasia by bone marrow biopsy confirming clonal plasma
cell population
- eGFR <40 ml/min/1.73m2 or 24h urine total protein > 1gm
Inclusion criteria for both cast nephropathy associated with MM and other MGRS associated
renal diseases
- Subjects must be ≥ 18 years of age at time of registration.
- Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status
of 0, 1, or 2 ≤ 14 days prior to registration.
- No evidence of unequivocal recent nephrotoxic exposure (NSAIDs, radiocontrast...)
- No evidence of obstructive nephropathy by ultrasound
- Subjects must have adequate hematology laboratory values within 14 days prior to
registration defined by the following:
- Neutrophils ≥ 1.0 × 10^9 /L (Patients cannot have received G-CSF or GM-CSF
within 1 week of screening or pegfilgrastim within 2 weeks of screening to meet
eligibility).
- Platelets ≥ 100 × 10^9 /L for run-in and 75 × 10^9 /L for phase II (Note:
Platelet support is not permitted to help participants meet eligibility
criteria).
- hemoglobin ≥ 7.5 g/dL without prior red blood cells [RBC] transfusion within 7
days before the laboratory test; recombinant human erythropoietin use is
permitted.
- Subjects must have adequate hepatic function laboratory values ≤ 14 days prior to
registration:
- Aspartate aminotransferase (AST), alkaline phosphatase (AP) or alanine
aminotransferase (ALT) ≤ 3 × the upper limit of normal (ULN)
- Total bilirubin ≤ 1.5 x ULN except for patients with a history of elevated
total bilirubin, such as in Gilbert's.
- Hepatic Child-Pugh score at worse A (patients are eligible for the phase 2 part
but not for the Run-in-Period of the trial).
- Female patients will have to satisfy the following criteria:
- Be postmenopausal for at least 1 year Prior to registration visit, OR
- Be surgically sterile, OR
- If of childbearing potential, agree to practice 2 effective methods of
contraception, at the same time, from the time of signing the informed consent
form through 90 days after the last dose of study drug, OR
- Agree to practice true abstinence when this is in line with the preferred and
usual lifestyle of the subject. (Periodic abstinence [e.g., calendar,
ovulation, symptothermal, post-ovulation methods] and withdrawal are not
acceptable methods of contraception). If patient is female and of childbearing
potential, she must have a negative serum beta human chorionic gonadotropin
(β-HCG) test < 14 days prior to registration and consent to ongoing pregnancy
testing during the course of the study.
- Male patients, even if surgically sterilized (i.e., status post-vasectomy), must
agree to one of the following
- Practice effective barrier contraception during the entire study treatment
period and through 90 days after the last dose of study drug, OR
- Practice true abstinence when this is in line with the preferred and usual
lifestyle of he subject. (Periodic abstinence [e.g., calendar, ovulation,
symptothermal, postovulation methods] and withdrawal are not acceptable methods
of contraception).
- Subjects must have the willingness and ability to comply with scheduled visits,
treatment plan, laboratory tests, study procedures, and research procedures.
Exclusion Criteria:
- MGRS associated with diseases other than plasma cell dyscrasia (e.g. CLL, B-cell
neoplasm, Waldenstrom's macroglobulinemia...)
- Plasma cell leukemia, AL amyloidosis, or POEMS syndrome.
- Treatment with prior drugs aimed at the plasma cell dyscrasia.
- Treatment with prior or concurrent investigational agents aimed at the plasma cell
dyscrasia.
- Female patients who are lactating or have a positive serum pregnancy test during the
screening period.
- Major surgery ≤ 14 days before registration.
- Focal radiation therapy within 14 days prior to registration with the exception of
palliative- radiotherapy for symptomatic management but not on measurable
extramedullary plasmacytoma.
- Disease-related central nervous system involvement.
- The subject has uncontrolled significant intercurrent illness including, but not
limited to, ongoing or active infection.
- Clinically significant cardiac disease, including:
- Myocardial infarction within 6 months before randomization, or unstable or
uncontrolled disease/condition related to or affection cardiac function (e.g.,
unstable angina, congestive heart failure, New York Heart Association Class
III-IV)
- Uncontrolled cardiac arrhythmia
- Any serious medical or psychiatric illness that could, in the investigator's
opinion, potentially interfere with the completion of treatment according to this
protocol.
- Known allergy to any of the study medications, their analogues, or excipients in the
various formulations of any agent.
- Concurrent malignancy except for treated non-melanoma skin cancer, cervical
carcinoma in situ and low-risk prostate CA being monitored without treatment.
- Grade 2 or higher peripheral neuropathy on clinical examination during the screening
period.
- Chemotherapy ≤ 14 days of registration.
- Exposure to an investigational drug (including investigational vaccine) or invasive
investigational medical device for any indication within 4 weeks or 5
pharmacokinetic halflives, whichever is longer.
- Patients with known chronic obstructive pulmonary disease (COPD) with a forced
expiratory volume in 1 second (FEV1) <50% of predicted normal; moderate or severe
persistent asthma within the past 2 years. Note that FEV1 testing is required for
participants suspected of having COPD and participants must be excluded if FEV1 is
<50% of predicted normal
- Moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma
of any classification. Note that participants who currently have controlled
intermittent asthma or controlled mild persistent asthma are allowed to participate.
- Patients who have a contraindication to the use of any form of anticoagulation or
antiplatelet agents.
- The use of strong CYP3A4 and CYP1A2 inducers or inhibitors will not be allowed while
patients are treated on this study.
- Patients with Hepatic Child-Pugh score B and C. Note that patients with Hepatic
Child-Pugh score A are excluded from the Run-in-Period of the trial
- Patient is:
- Known history of human immunodeficiency virus (HIV) and those who are
seropositive for HIV.
- Seropositive for hepatitis B (defined by a positive test for hepatitis B
surface antigen [HBsAg]). Subjects with resolved infection (ie, subjects who
are HBsAg negative but positive for antibodies to hepatitis B core antigen
[anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be
screened using real-time polymerase chain reaction (PCR) measurement of
hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be
excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV
vaccination (anti-HBs positivity as the only serologic marker) AND a known
history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR.
- Seropositive for hepatitis C (except in the setting of a sustained virologic
response [SVR], defined as aviremia at least 12 weeks after completion of
antiviral therapy).
- Vaccination with live attenuated vaccines within 4 weeks of first study agent
administration.
- Plasmapheresis within 28 days before randomization.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Tufts Medical Center (Data Collection Only)
Address:
City:
Boston
Zip:
02111
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Raymond L Comenzo, MD
Phone:
617-636-6454
Facility:
Name:
Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
Address:
City:
Basking Ridge
Zip:
07920
Country:
United States
Status:
Recruiting
Contact:
Last name:
Hani Hassoun, MD
Phone:
646-608-3718
Facility:
Name:
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
Address:
City:
Middletown
Zip:
07748
Country:
United States
Status:
Recruiting
Contact:
Last name:
Hani Hassoun, MD
Phone:
646-608-3718
Facility:
Name:
Memorial Sloan Kettering Bergen (Limited Protocol Activities)
Address:
City:
Montvale
Zip:
07645
Country:
United States
Status:
Recruiting
Contact:
Last name:
Hani Hassoun, MD
Phone:
646-608-3718
Facility:
Name:
Memorial Sloan Kettering Cancer Center Suffolk - Commack (Limited Protocol Activities)
Address:
City:
Commack
Zip:
11725
Country:
United States
Status:
Recruiting
Contact:
Last name:
Hani Hassoun, MD
Phone:
646-608-3718
Facility:
Name:
Memorial Sloan Kettering Westchester (Limited Protocol Activities)
Address:
City:
Harrison
Zip:
10604
Country:
United States
Status:
Recruiting
Contact:
Last name:
Hani Hassoun, MD
Phone:
646-608-3718
Facility:
Name:
Weill Cornell Medical Center (Data Collection Only)
Address:
City:
New York
Zip:
10021
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Jorge Monge, MD
Email:
jum9127@med.cornell.edu
Facility:
Name:
Mount Sinai Hospital (Data Collection Only)
Address:
City:
New York
Zip:
10029
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Adriana Rossi, MD
Phone:
212-241-7873
Facility:
Name:
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
Address:
City:
New York
Zip:
10065
Country:
United States
Status:
Recruiting
Contact:
Last name:
Hani Hassoun, MD
Phone:
646-608-3718
Contact backup:
Last name:
Carlyn R Tan, MD
Phone:
646-608-3778
Facility:
Name:
Memorial Sloan Kettering Nassau (Limited Protocol Activities)
Address:
City:
Uniondale
Zip:
11553
Country:
United States
Status:
Recruiting
Contact:
Last name:
Hani Hassoun, MD
Phone:
646-608-3718
Start date:
October 16, 2023
Completion date:
October 2026
Lead sponsor:
Agency:
Memorial Sloan Kettering Cancer Center
Agency class:
Other
Collaborator:
Agency:
Janssen Pharmaceuticals
Agency class:
Industry
Source:
Memorial Sloan Kettering Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06083922
http://www.mskcc.org/mskcc/html/44.cfm
