Trial Title:
IMMUNOPLANT for Newly Diagnosed Multiple Myeloma
NCT ID:
NCT06376526
Condition:
Multiple Myeloma
Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
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:
Biological
Intervention name:
Linvoseltamab
Description:
Participants will be administered Linvoseltamab intravenously (IV), using a step-up
dosing schedule as follows:
- Cycle 1, Day 1: 5mg
- Cycle 1, Day 8: 25mg
- Cycle 1, Days 15 and 22: 200mg
- Cycles 2 and 3, Days 1, 8, 15 and 22: 200mg
- Cycle 4, Days 1 and 15: 200mg.
For participants who are MRD-positive after four (4) cycles of study treatment:
- Cycles 5 and 6, Days 1 and 15: 200 mg
Arm group label:
Linvoseltamab Group
Summary:
The purpose of this study is to determine whether Linvoseltamab therapy in patients with
newly diagnosed multiple myeloma will convert the disease status from minimal residual
disease (MRD)-positive to MRD-negative, and increase the length of time that the disease
is controlled. The researchers also want to find out the effects (good and bad) that
Linvoseltamab has on participants and the condition.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Diagnosis of newly-diagnosed multiple myeloma (NDMM) per International Myeloma
Working Group (IMWG) criteria documented initially prior to induction treatment.
2. Documentation of having received a triplet or quadruplet based initial combination
therapy containing at least two of the following: Immunomodulatory drug (IMiD),
proteosome inhibitor (PI), and/or anti-cluster of differentiation 38 (anti-CD38).
3. Documentation of attaining a best response of very good partial response (VGPR) or
better but MRD+ (sensitivity: ≤10^-5) after at least 4 cycles of combination
therapy.
Note: Patients who at baseline prior to initial combination therapy did not have
IMWG evaluable disease and therefore a response assessment of VGPR was unable to be
made but currently have residual MM by M-protein and/or involved light chains and/or
MRD positivity may enroll. Also, patients who have no apparent bone marrow (BM)
residual disease but rather extramedullary disease as evidenced by positron emission
tomography (PET)/computed tomography (CT) may enroll.
4. Age ≥18 years.
5. Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 1. Patients with
ECOG 2 solely due to local symptoms of myeloma (eg, pain) may be allowed after
discussion with the PI (APPENDIX A).
6. Adequate organ function, which is defined as follows:
- a. Absolute neutrophil count (ANC) ≥1,000 cells/microliter (mcL) (unless
patient has ethnic/cyclic neutropenia or if neutropenia is thought to be due to
MM)
- b. Platelets ≥50,000 platelets/mcL
- c. Hemoglobin ≥8 g/dL (transfusions permitted)
- d. Serum total bilirubin ≤ 1.5 X upper limit of normal (ULN) or direct
bilirubin ≤ ULN for patients with total bilirubin levels > 1.5 ULN (except
patients with Gilbert's syndrome who must have a total bilirubin of <3 X ULN)
- e. Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
(SGOT)) and alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase
(SGPT)) ≤ 2.5 X ULN
- f. Serum creatinine ≤ 1.5 X ULN (except if due to myeloma) or estimated
glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 (note that measured
glomerular filtration rate [GFR], ie, 24-hour urine, can also be used) based on
institutional standard
- g. Female patients of childbearing potential must have a negative serum
pregnancy test at Screening. Female patients of childbearing potential and
fertile male patients who are sexually active with a female of childbearing
potential must use highly effective methods of contraception throughout the
study and for 6 months following the last dose of study treatment. For more
information on contraception requirements, please refer to Section 4.11.
- h. Willing and able to provide written informed consent in accordance with
federal, local, and institutional guidelines. The patient must provide informed
consent prior to the first screening procedure. For more information on the
informed consent process, please refer to Section 15.1.
7. Willing and able to comply with clinic visits and study-related procedures.
Exclusion Criteria:
1. Patients who have received prior systemic therapies for MM other than initial
IMiD/PI/anti-CD38-based combination therapy (receiving limited cycles of other
induction therapies, eg, cyclophosphamide, bortezomib and dexamethasone (CyBorD) or
pulse dexamethasone prior to main induction is allowed). Exclusions include
high-dose melphalan with autologous stem cell transplant (HDM-ASCT) and allogeneic
stem cell transplant (SCT).
Note: Continuous systemic corticosteroid treatment with more than 10 mg per day of
prednisone or anti-inflammatory equivalent within 72 hours of start of study drug is
not permitted.
2. Patients who are receiving any other investigational agents for any reasons.
3. Patients who receive a live attenuated vaccine within 4 weeks of scheduled study
treatment administration.
4. Contraindication to any concomitant medication, including those medications
administered for infusion reaction, antiviral, antibacterial, anticoagulation, tumor
lysis, or hydration prophylaxis given prior to therapy (Sections 4.8, 4.9, and 7).
5. Patient has any of the following:
1. Human immunodeficiency virus (HIV)-positive with 1 or more of the following:
- i. History of acquired immune deficiency syndrome (AIDS)-defining
conditions cluster of differentiation 4 (CD4) count <350 cells/mm3
- ii. Detectable viral load during screening or within 6 months prior to
screening
- iii. Not receiving highly active anti-retroviral therapy
- iv. Had a change in anti-retroviral therapy within 6 months of the start
of screening
- v. Receiving anti-retroviral therapy that may interfere with study
treatment as assessed after discussion with the Sponsor-Investigator in
consultation with study pharmacist
2. Hepatitis B infection (ie, hepatitis B surface antigen (HBsAg) or hepatitis B
virus (HBV)-deoxyribonucleic acid [DNA] positive). Patients with resolved
infection (ie, patients 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 HBV DNA levels. Those who are PCR positive will be
excluded. In the event the infection status is unclear, quantitative viral
levels are necessary to determine the infection status. EXCEPTION: Patients
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.
3. Active hepatitis C infection as measured by positive hepatitis C virus
(HCV)-ribonucleic acid (RNA) testing. Participants with a history of HCV
antibody positivity must undergo HCV-RNA testing. If a participant with history
of chronic hepatitis C infection (defined as both HCV antibody and HCV RNA
positive) completed antiviral therapy and has undetectable HCV-RNA 12 weeks
following the completion of therapy, the participant is eligible for the study.
6. History of allergic reactions attributed to compounds of similar chemical or
biologic composition to the experimental agents used in study.
7. Female patient refuses to discontinue breastfeeding her infant during study
treatment or within 6 months after receiving the last dose of study treatment
(Section 4.11).
8. Women of childbearing potential (WOCBP) and men who are unwilling to practice highly
effective contraception prior to the initial dose/start of the first treatment,
during the study, and for at least 6 months after the last dose.
- Highly effective contraceptive measures for women include: stable use of
combined (estrogen and progestogen containing) hormonal contraception (oral,
intravaginal, transdermal) or progestogen-only hormonal contraception (oral,
injectable, implantable) associated with inhibition of ovulation initiated 2 or
more menstrual cycles prior to screening intrauterine device (IUD);
intrauterine hormone-releasing system (IUS) bilateral tubal ligation
vasectomized partner (provided that the male vasectomized partner is the sole
sexual partner of the study participant and that the partner has obtained
medical assessment of surgical success for the procedure) and/or sexual
abstinence.
- WOCBP are defined as women who are fertile following menarche until becoming
post-menopausal, unless permanently sterile. Permanent sterilization methods
include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A
post-menopausal state is defined as no menses for 12 months without an
alternative medical cause. A high follicle stimulating hormone (FSH) level in
the postmenopausal range may be used to confirm a post-menopausal state in
women not using hormonal contraception or hormonal replacement therapy.
However, in the absence of 12 months of amenorrhea, a single FSH measurement is
insufficient to determine the occurrence of a post-menopausal state.
- Male study participants with WOCBP partners are required to use condoms unless
they are vasectomized or practice sexual abstinence. Male study participants
should not donate sperm during the study, and for at least 6 months after the
last dose. Vasectomized partner or vasectomized study participant must have
received medical assessment of the surgical success.
- Sexual abstinence is considered a highly effective method only if defined as
refraining from heterosexual intercourse during the entire period of risk
associated with the study treatments. The reliability of sexual abstinence
needs to be evaluated in relation to the duration of the clinical trial and the
preferred and usual lifestyle of the patient.
Note: Periodic abstinence (calendar, symptothermal, post-ovulation methods),
withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method
(LAM) are not acceptable methods of contraception. Female condom and male condom
should not be used together (Section 4.11).
9. Presence of the following cardiac conditions:
- e. New York Heart Association stage III or IV congestive heart failure
- f. Myocardial infarction or coronary artery bypass graft ≤ 6 months prior to
study enrollment
- g. History of clinically significant ventricular arrhythmia or unexplained
syncope, not believed to be vasovagal in nature or due to dehydration.
Uncontrolled cardiac arrhythmia or clinically significant electrocardiogram
(ECG) abnormalities
- h. Unstable or uncontrolled disease/condition related to or affecting cardiac
function (eg, unstable angina)
10. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, venous thromboembolic disease, hemorrhage, pulmonary fibrosis,
pneumonitis, neurological condition, active autoimmune disease or a documented
history of autoimmune disease with the exception of vitiligo, type I diabetes, and
prior autoimmune thyroiditis that is currently euthyroid based on clinical symptoms
and laboratory testing, or psychiatric illness/social situations within 2 weeks that
would limit compliance with study requirements.
11. Active malignancy other than MM requiring treatment in the past 12 months.
Malignancies treated within the past 12 months that are considered cured with
minimal risk of recurrence are allowed.
12. Have any condition that, in the opinion of the Investigator, would compromise the
well-being of the patient or the study or prevent the patient from meeting or
performing study requirements.
13. Patients with impaired decision-making capacity will not be enrolled on this trial.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of Miami
Address:
City:
Miami
Zip:
33136
Country:
United States
Status:
Recruiting
Contact:
Last name:
Dickran Kazandjian, MD
Phone:
305-243-5001
Email:
dkazandjian@miami.edu
Contact backup:
Last name:
Dickran Kazandjian, MD
Start date:
August 21, 2024
Completion date:
August 31, 2029
Lead sponsor:
Agency:
Dickran Kazandjian, MD
Agency class:
Other
Collaborator:
Agency:
Regeneron Pharmaceuticals
Agency class:
Industry
Source:
University of Miami
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06376526
