Trial Title:
Elimination of Minimal Residual Disease After Transplant
NCT ID:
NCT05690984
Condition:
Multiple Myeloma
Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasm, Residual
Dexamethasone
Lenalidomide
Conditions: Keywords:
minimal residual disease
multiple myeloma
next-generation sequencing
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Dexamethasone
Description:
Dexamethasone will be used for the double purpose of premedication and therapeutic
effect. On Day 1 of Cycle 1, subjects will be administered 40 mg dexamethasone as an IV
infusion. On Days 8, 15, 22 of Cycle 1 and Days 1 and 15 of Cycles 2-4, dexamethasone
will be given as a single oral dose of 40 mg. For Cycles 5-12, dexamethasone will be
given as a single oral dose of 4 mg on Days 1 and 15.
Arm group label:
Isatuximab in combination with lenalidomide and dexamethasone.
Other name:
Decadron
Other name:
Dexasone
Other name:
Diodex
Other name:
Hexadrol
Other name:
Maxidex
Intervention type:
Drug
Intervention name:
Isatuximab
Description:
Following premedication (if applicable), subjects will be given isatuximab 10 mg/kg body
weight as an intravenous (IV) infusion on Days 1, 8, 15, and 22 (i.e., weekly) during
Cycle 1 and on Days 1 and 15 (i.e., Q2W) during Cycles 2-12.
Arm group label:
Isatuximab in combination with lenalidomide and dexamethasone.
Other name:
Sarclisa
Intervention type:
Drug
Intervention name:
Lenalidomide
Description:
On Days 1-21 for all 12 cycles, lenalidomide will be given to subjects as a single daily
oral dose.
Arm group label:
Isatuximab in combination with lenalidomide and dexamethasone.
Other name:
Revlimid
Summary:
This is a single-center, single-arm, phase II study that will enroll multiple myeloma
(MM) patients with persistent bone marrow minimal residual disease (MRD) post autologous
stem cell transplant (ASCT) irrespective of the International Myeloma Working Group
(IMWG) response.
Detailed description:
Thirty-one study subjects will be enrolled at Froedtert Hospital and the Medical College
of Wisconsin Cancer Center. Enrolled subjects will receive a combination of isatuximab,
lenalidomide, and dexamethasone (IsaRD) for 12 28-day cycles. The primary objective of
this study is to determine bone marrow (BM) MRD ≤1x10^5 negativity rate, as measured by
the clonoSEQ® next-generation sequencing (NGS) assay, at the end of 12 months of IsaRD
treatment. Other objectives will further assess efficacy, tolerability, and molecular
response to the IsaRD regimen.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age ≥18 years.
2. Eastern Cooperative Oncology Group (ECOG) Performance Status criteria of 0-2.
3. Must have archival bone marrow sample at time of diagnosis that can be used for
clonality identification for NGS if not already performed.
4. Presence of residual bone marrow minimal residual disease (MRD) positivity by
clonoSEQ® next-generation sequencing (NGS) 90-120 days post autologous stem cell
transplantation.
5. Histologically confirmed diagnosis of symptomatic multiple myeloma (patients with
multiple myeloma with secondary amyloidosis are eligible, but no amyloid treatment
will be allowed while on study).
6. Received autologous stem cell transplant as upfront therapy for myeloma (defined as
ASCT within one year of diagnosis of symptomatic MM).
7. Adequate organ function as defined below:
- Absolute neutrophil count (ANC) ≥1,000/mm^3.
- Platelet count ≥75,000/mm^3; platelet transfusions to help patients meet
eligibility criteria are not allowed within seven days before study enrollment.
- Total bilirubin ≤1.5 x the upper limit of the normal range (ULN)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 x ULN
8. Pregnancy It is not known what effects this treatment has on human pregnancy or
development of the embryo or fetus. Therefore, female subjects participating in this
study should avoid becoming pregnant, and male subjects should avoid impregnating a
female partner. Non-sterilized female subjects of reproductive age and male subjects
should use effective methods of contraception through defined periods during and
after study treatment as specified below.
Female participants: A female participant is eligible to participate if she is not
pregnant, not breastfeeding, and at least one of the following conditions applies:
- Not a female of childbearing potential (FCBP), OR
- A FCBP who must have a negative serum or urine pregnancy test with a
sensitivity of at least 25 mIU/mL within 10-14 days prior to and again within
24 hours prior to starting study medication and before each cycle of study
treatment and must either commit to continue abstinence from heterosexual
intercourse or apply a highly effective method of birth control during the
intervention period and for at least five months after the last dose of
isatuximab treatment Male participants: A male participant, even if surgically
sterilized (i.e., status post-vasectomy), must agree to use contraception
during the intervention period and for at least five months after the last dose
of isatuximab treatment and refrain from donating sperm during this period.
9. All study participants must be registered into the mandatory Revlimid REMS® program
and be willing to comply with its requirements.
10. Ability to understand a written informed consent document, and the willingness to
sign it.
Exclusion Criteria:
1. Evidence of MM disease progression any time prior to enrollment.
2. Administration or planned administration of any other concomitant chemotherapy,
immunotherapy, or any ancillary therapy that would be considered a treatment of
multiple myeloma from Day +30 post-transplant through discontinuation from study.
Local radiation therapy is allowed. Subjects may be on corticosteroids if they are
being given for disorders other than multiple myeloma (e.g., adrenal insufficiency,
rheumatoid arthritis, etc.)
3. Any serious medical or psychiatric illness that could, in the investigator's
opinion, potentially interfere with the completion of treatment according to this
protocol.
4. Prior organ transplant requiring immunosuppressive therapy.
5. Known to be human immunodeficiency virus (HIV) positive.
6. Known to have hepatitis A, B, or C active infection. If hepatitis positive, patient
may still be per the notes below.
• Uncontrolled or active hepatitis B virus (HBV) infection: Patient with positive
HBsAg and/or HBV DNA.
Of Note:
- Patient can be eligible if anti-HBc IgG positive (with or without positive
anti-HBs) but HBsAg and HBV DNA are negative.
- If anti-HBV therapy in relation with prior infection was started before
initiation of investigational medicinal product, the anti-HBV therapy and
monitoring should continue throughout the study treatment period.
- Patient with negative HBsAg and positive HBV DNA observed during screening
period will be evaluated by a specialist for start of anti-viral treatment:
study treatment could be proposed if HBV DNA becomes negative and all the other
study criteria are still met.
- Active hepatitis C virus (HCV) infection: positive HCV RNA and negative
anti-HCV.
Of Note:
- Patients with antiviral therapy for HCV started before initiation of
investigational medicinal product and positive HCV antibodies are eligible. The
antiviral therapy for HCV should continue throughout the treatment period until
seroconversion.
- Patients with positive anti-HCV and undetectable HCV RNA without antiviral
therapy for HCV are eligible.
7. Known allergy to any of the study medications, their analogues, or excipients in the
various formulations of any agent.
8. Concurrent hematologic or non-hematologic malignancy requiring treatment (other than
multiple myeloma and secondary amyloidosis).
9. Cardiac syncope, uncompensated New York Heart Association (NYHA) Class 3 or 4
congestive heart failure, myocardial infarction within the previous six months,
unstable angina pectoris, clinically significant repetitive ventricular arrhythmias
despite antiarrhythmic treatment, severe orthostatic hypotension, or clinically
important autonomic disease.
10. Major surgery within 14 days prior to start of study treatment (Note: vertebroplasty
and kyphoplasty are not considered major surgery).
11. Infection requiring systemic antibiotic therapy or other serious infection within 14
days prior to start of study treatment.
12. Participation in other clinical trials, including those where a subject received an
investigational drug within 30 days or five half-lives of the investigational drug
prior to start of study treatment, whichever is longer.
13. Any clinically significant, uncontrolled medical conditions that, in the
investigator's opinion, would expose the subject to excessive risk or may interfere
with compliance or interpretation of the study results.
14. Hypersensitivity or history of intolerance to steroids, mannitol, pregelatinized
starch, sodium stearyl fumarate, histidine (as base and hydrochloride salt),
arginine hydrochloride, poloxamer 188, sucrose or any of the other components of
study intervention that are not amenable to premedication with steroids and H2
blockers or would prohibit further treatment with these agents.
15. Pregnant or breastfeeding subjects.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Froedtert Hospital & the Medical College of Wisconsin
Address:
City:
Milwaukee
Zip:
53226
Country:
United States
Status:
Recruiting
Contact:
Last name:
Meera Mohan, MD
Phone:
414-805-4600
Email:
memohan@mcw.edu
Investigator:
Last name:
Meera Mohan, MD
Email:
Principal Investigator
Start date:
June 26, 2023
Completion date:
July 2026
Lead sponsor:
Agency:
Medical College of Wisconsin
Agency class:
Other
Source:
Medical College of Wisconsin
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05690984
