This study has been transitioned to CTIS with ID 2024-513075-40-00 check the CTIS register for the current data. To evaluate the efficacy of blmf in patients with relapsed or refractory AL amyloidosis.
ID
Source
Brief title
Condition
- Plasma cell neoplasms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Endpoint: The primary end point of the study is the CR/VGPR/low-dFLC
response rate at 6 months/4 cycles from start of therapy with blmf, according
to consensus response criteria.
Stratification Factors: This is a single arm study; no stratification is
required for disposition to treatment arms
Secondary outcome
Secondary Endpoints
Safety
1. Rates of grade 3 or higher AEs related to blmf therapy,
2. Rates of treatment discontinuation due to toxicity related to blmf,
3. Dose reduction due to toxicity of blmf therapy,
4. Any grade hematologic AEs,
5. Any grade non-hematologic AEs,
6. Rates of AEs of special interest (Ocular toxicity)
Efficacy
1. Overall hematologic response rates at 3 and at 6 months (CR + VGPR +
low-dFLC response + PR),
2. Organ response rates per individual organ (heart, kidney, liver) at 3, 6,
12, 18 and 24 months from start of therapy,
3. Time to first hematologic response (CR/VGPR/low-dFLC response/PR),
4. Time to at least a very good hematologic response (VGPR or better),
5. Time to at least a low-dFLC response (low-dFLC response or CR),
6. Duration of hematologic response (time from first response to hematologic
progression, for those who achieved at least a hemPR or low-dFLC response)
7. Time to a subsequent therapy, either due to progression or inadequate
response,
8. Time to hematologic progression or major organ deterioration or death,
9. Overall survival,
10. Quality of life
Background summary
AL Amyloidosis is considered a rare disease, for which no specific standard of
care therapies exist. Therefore, we continue to seek better treatment results
by means of new medicines for patients who are diagnosed with this disease.
Belantamab mafodotin is a type of monoclonal antibody (protein) that targets
and destroys a specific type of immune cells (plasma cells) in the body. These
plasma cells produce the abnormal proteins (the light chains) which form
amyloid in AL Amyloidosis.
Doctors cannot prescribe belantamab mafodotin yet (outside of a study).
However, belantamab mafodotin has been evaluated (and continues to be
evaluated) for its efficacy in patients with multiple myeloma (another disorder
of plasma cells), however, it does not have an approved indication for AL
Amyloidosis.
Study objective
This study has been transitioned to CTIS with ID 2024-513075-40-00 check the CTIS register for the current data.
To evaluate the efficacy of blmf in patients with relapsed or refractory AL
amyloidosis.
Study design
•This is an open-label, multicenter, Phase 2 study in patients with light chain
(AL) amyloidosis, previously treated, and requiring therapy.
•Approximately 35 patients will receive therapy with belantamab mafodotin
(blmf).
•The study has four phases: Screening Phase, Treatment Phase, Post-Treatment
Observation Phase, and Long-term Follow-up Phase
•A safety run-in will be conducted in six patients treated with blmf for at
least one cycle.
Dosing of these six patients will be staggered so that no patient receives
their first dose earlier than 48 hours after the previously enrolled patient.
Safety evaluation will be performed by the sponsor after all six patients
complete at least one therapy cycle. A Data Monitoring Committee (DMC),
consisting of two clinicians and one statistician, will be established to
review safety results. The evaluation of the safety run-in will not include
patients who will not have completed the first cycle of treatment for reasons
unrelated to the study treatment. More specifically, this refers to patients
who die, withdraw from the study, or discontinue study treatment for reasons
other than toxicity, i.e., disease progression, patient choice, patient lost to
follow-up. If a safety signal is detected and the DMC deems, in the
recommendation sent to the Sponsor, that the safety profile of the study
treatment is unfavorable, recruitment will be temporarily interrupted, and dose
and schedule of the drug will be re-evaluated. If no safety signal is observed,
enrollment will resume.
•Patients in the safety run-in will continue all scheduled assessments as
specified in the Time and Events Schedule in the protocol, and contribute to
the overall safety evaluation.
Intervention
Treatment will be given in 42 day Cycles for a maximum of 1 year (8 cycles), on
day 1 of every cycle.
Study burden and risks
As with all research studies, the study treatment and study procedures may
involve unknown risks. Any medication can have temporary or permanent side
effects that may or may not be expected.
The most common side effects occurring in more than 10% of subjects (10 or more
out of 100 patients) were:
o Eye problems: blurred vision, dry/itchy eyes, changes in vision, eye
discomfort, , difficulty seeing at night, inflammation or other changes of
front part of eye.
o Low number of blood cells called platelets (thrombocytopenia), which may
cause bleeding and easy bruising. Bleeding may be serious, or life threatening
and may require a transfusion.
o Feeling tired (fatigue)
o Having fewer red blood cells than normal (anemia).
o Feeling sick to your stomach (nausea)
o Abnormal liver tests
o Fever (if you have a fever, please contact your trial doctor immediately)
o Pneumonia, or other lung infections
o Cold or cold-like symptoms (upper respiratory tract infection)
o Low number of certain types of white blood cells called neutrophils
(neutropenia) and lymphocytes (lymphopenia), which could increase the risk of
infection. If you have a fever, please contact your trial doctor immediately
o Diarrhoea
o Reactions from the infusion of belantamab mafodotin, usually happen within
the first 24 hrs after the infusion. Symptoms may include: flushing, chills,
fever, difficulty breathing, rapid heartbeat or a drop-in blood pressure
(feeling light-headed).
Other common side effects seen in 1% to 10% of subjects (between 1 to 10 out of
100 people) were:
o Other eye problems: eye irritation, abnormal sensitivity of the eyes to
light, and sores on the eyes possibly with infection.
o Increased albumin, a type of protein, in the urine (albuminuria)
o An increase in an enzyme released into the blood when muscle is damaged
(creatine phosphokinase)
o Vomiting
In another study which is testing belantamab mafodotin in combination with two
medicines already approved for the treatment of Relapsed/Refractory Multiple
Myeloma (RRMM), called lenalidomide and dexamethasone, two patients who had low
neutrophil counts developed serious infections which led to death.
If you have fever at any point while you are in this study, please contact your
study doctor immediately.
Possible Side effects from tests
•Blood draw: Taking blood may cause bruising at the place where the needle goes
into the skin. Fainting, and in rare cases infection, may occur.
•X-Ray Risks: The radiation dose that is in the x-ray(s) taken for this study
is small. There is no significant risk from this amount of radiation.
•ECG Risk: There is generally no risk with having an ECG. The sticky patches
may pull your skin or cause redness or itching.
•CT scan Risk: CT scans do create low levels of radiation, which has a small
potential to cause cancer and other defects. However, the risk associated with
any one scan is small.
•MRI Risk: There are no known risks or side effects with having an MRI. If a
contrast material is used, your study doctor will tell you about possible side
effects or allergic reaction.
•Risk of bone marrow investigations (biopsy/aspirate): The area around where
the aspirate and/or biopsy are taken is numbed using an injection of numbing
medication. You may experience pain and discomfort during and after the
procedure. There is also a risk of infection and of bleeding from the biopsy
site. You could also have an allergic reaction to the numbing medication. If
you have a prior history of allergies, you should inform your study doctor.
Embryo-fetal toxicity: belantamab mafodotin may harm an unborn baby.
Fertility: belantamab mafodotin treatment may affect men and women*s ability to
have children.
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NL
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Age
Inclusion criteria
1.Diagnosis of AL amyloidosis, confirmed by histology and typed with
immunohistochemistry, immunoelectron microscopy or mass spectrometry, or if not
available, for patients with biopsy confirmed amyloidosis and cardiac
involvement alone, if they also have a negative PYP- or DPD-Tc99m bone scan.
2..Patients must have had at least two cycles of therapy directed against
plasma cell clone. However, patients that have received high dose therapy with
melphalan as their only therapy are also eligible. 3.Patients must be 18 years
of age or above. 4.ECOG performance status 0, 1 or 2. 5.Mayo stage 1 or Mayo
stage 2 or Mayo stage 3A1-3 defined as both cTnT < 0.035 ng/mL (or in place of
cTnT the cTnI < 0.10 ng/mL or high sensitivity Troponin T < 54 ng/L) AND
simultaneous NT-proBNP <= 332 ng/L, OR EITHER above threshold, or BOTH above
threshold but with NTproBNP < 8500 ng/L (stage 3A disease) 6.Supine systolic
blood pressure >= 90 mmHg. 7.Measurable disease defined by at least one of the
following: a.serum free light chain (FLC) >=2.0 mg/dL (20 mg/L) with an abnormal
kappa:lambda ratio or the difference between involved and uninvolved free light
chains (dFLC) >=2mg/dL (20 mg/L). b.presence of a monoclonal spike that is >=0.5
g/dl. 8.Symptomatic organ involvement (heart, kidney, liver/GI tract,
peripheral nervous system). 9.Written informed consent in accordance with local
and institutional guidelines. 10.Female patients: contraceptive use should be
consistent with local regulations regarding the methods of contraception for
those participating in clinical studies. A female patient is eligible to
participate if she is not pregnant or breast-feeding, and at least one of the
following conditions applies: a.She is not of childbearing potential (WOCBP) OR
b.She is a WOCBP and using, during the intervention period and for at least 4
months after the last dose of the trial, a contraceptive method that is highly
effective (failure rate <1% per year), preferably with low user dependency (as
described in Appendix 3). Patient agrees not to donate eggs (ova, oocytes) for
the purpose of reproduction during this period. The investigator should
evaluate the effectiveness of the contraceptive method in relationship to the
first dose of trial intervention. A WOCBP must have a negative highly sensitive
serum-pregnancy test (as required by local regulations) 72 hours before the
first dose of the trial intervention. The investigator is responsible for
reviewing the medical history, menstrual history, and recent sexual activity to
decrease the risk for inclusion of a woman with a nearly undetected pregnancy.
Nonchildbearing potential is defined as follows (by other than medical
reasons): a.>=45 years of age and has not had menses for >1 year b.Patients who
have been amenorrhoeic for <2 years without a history of hysterectomy and
oophorectomy must have a follicle stimulating hormone value in the
postmenopausal range after screening evaluation c.Post-hysterectomy,
post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or
oophorectomy must be confirmed with medical records of the actual procedure or
confirmed by an ultrasound. Tubal ligation must be confirmed with medical
records of the actual procedure. 12. Male patients: contraceptive use should be
consistent with local regulations regarding the methods of contraception for
those participating in clinical studies. Male patients are eligible to
participate if they agree to the following during the intervention period and
for 6 months after the last dose of trial treatment to allow for clearance of
any altered sperm: a.Refrain from donating sperm PLUS, either: b.Be abstinent
from heterosexual intercourse as their preferred and usual lifestyle (abstinent
on a long term and persistent basis) and agree to remain abstinent. OR c.Must
agree to use contraception/barrier as detailed below: Agree to use a male
condom, even if they have undergone a successful vasectomy, and female partner
agrees to use an additional highly effective contraceptive method with a
failure rate of <1% per year as when having sexual intercourse with a woman of
childbearing potential who is not pregnant. 13. All toxicities related to
previous treatment (defined by National Cancer Institute- Common Toxicity
Criteria for Adverse Events [NCI-CTCAE], version 5, corneal toxicities are
defined according to the Keratopathy Visual Activity [KVA] scale), must be <=
Grade 1 at the time of enrolment except for alopecia. 14. Patient must be able
to understand the trial procedures and agree to participate in the trial by
providing written informed consent.
Exclusion criteria
1.Presence of non-AL amyloidosis. 2.Presence of lytic bone lesions or active
myeloma with hypercalcemia, cast nephropathy, anemia due to marrow infiltration
or extramedullary disease > 60% plasma cells in bone marrow. 3.Previous
exposure to anti-BCMA agents 4.Cardiac stage IIIB disease: both cTnT > 0.035
ng/mL (or in place of cTnT the cTnI > 0.10 ng/mL or high sensitivity Troponin T
> 54 ng/L) AND simultaneous NT-proBNP >8500 ng/L. 5.Known repetitive
ventricular arrhythmias on 24h Holter Electrocardiograms (ECG) despite
anti-arrhythmic treatment. Patient must not have evidence of cardiovascular
risk including any of the following: •Evidence of current clinically
significant uncontrolled arrhythmias, including clinically significant ECG
abnormalities such as 2nd degree (Mobitz Type II) or 3rd degree
atrioventricular (AV) block. •History of myocardial infarction, acute coronary
syndromes (including unstable or uncontrolled angina), coronary angioplasty, or
stenting or bypass grafting within three (3) months of screening. •Class III or
IV heart failure as defined by the New York Heart Association functional
classification system (NYHA, 1994). •Severe uncontrolled ventricular
arrhythmias, sick sinus syndrome, electrocardiographic evidence of acute
ischemia or Grade 3 conduction system abnormalities (unless patient has a
pacemaker). •Uncontrolled hypertension or hypotension (i.e., supine SBP< 90
mmHg despite supportive therapy with midodrine) 6.Significant neuropathy
(Grades 3-4, or Grade 2 with pain) within 14 days prior to Cycle 1 Day 1.
7.Pleural effusions requiring thoracentesis or ascites requiring paracentesis
within 14 days prior to Cycle 1 Day 1. 8.Ongoing corneal epithelial disease
except mild changes in corneal epithelium (mild punctate keratopathy).
9.Current unstable liver or biliary disease defined by the presence of ascites,
encephalopathy, coagulopathy, hypoalbuminemia (except due to related nephrotic
syndrome), esophageal or gastric varices, persistent jaundice, or cirrhosis.
Note: Stable non-cirrhotic chronic liver disease (including Gilbert*s syndrome
or asymptomatic gallstones) or hepatobiliary involvement of malignancy is
acceptable if otherwise meets entry criteria. 10.Active renal condition
(infection, requirement for dialysis or any other condition that could affect
the patient*s safety) unrelated to AL amyloidosis. Patients with isolated
proteinuria resulting from AL are eligible, provided they fulfil other
inclusion criteria. 11.Patient must not use contact lenses while participating
in this trial. 12.Patient must not be simultaneously enrolled in any
interventional clinical trial. 13.Use of an investigational drug or approved
systemic anti-myeloma therapy (including systemic steroids) within 14 days or
five half-lives, whichever is shorter, prior to the first dose of trial drug.
14.Plasmapheresis within seven days prior to the first dose of the trial
treatment. Serious conditions unrelated to AL, such as SARS-CoV-2, may be
permitted but need to be discussed with the medical doctor and trial-site
personnel. 15.Treatment with a monoclonal antibody within 30 days prior to the
first dose of the trial treatment 16.Major surgery <= 4 weeks prior to
initiating trial treatment. 17.Evidence of active mucosal or internal bleeding
18.Known immediate or delayed hypersensitivity reaction or idiosyncratic
reactions to blmf or drugs chemically related to blmf, or any of the components
of the trial treatment. 19.Active infection requiring treatment. 20.Known HIV
infection (defined as positive testing for human immunodeficiency virus [HIV]
antibodies). 21.Positive test for hepatitis B surface antigen (HBsAg), or
hepatitis B core antibody (HBcAb) at screening or within 3 months prior to the
first dose of trial treatment. 22.Positive test for hepatitis C antibody
hepatitis C RNA at screening or within 3 months prior to the first dose of the
trial treatment. 23.Invasive malignancies other than the disease under study,
unless the second malignancy has been medically stable for at least 2 years
and, in the opinion of the principal investigators, will not affect the
evaluation of the effects of the clinical trial treatments of the currently
targeted malignancy. Patients with curatively treated non-melanoma skin cancer
may be enrolled without a 2-year restriction. 24.Any serious and/or unstable
pre-existing medical, psychiatric disorder, or other conditions (including lab
abnormalities) that could interfere with the patient*s safety, informed consent
or compliance to the trial procedures. 25.Patients must not be pregnant or
breast-feeding. 26. Participant must not have received a live or
live-attenuated vaccine within 30 days prior to first dose of belantamab
mafodotin.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-513075-40-00 |
| EudraCT | EUCTR2020-004001-32-NL |
| CCMO | NL75978.056.20 |