A Study of Belantamab Mafodotin in Patients With Relapsed or Refractory AL Amyloidosis

• Register: ClinicalTrials.gov
• Last refreshed on: 21 October 2024
• Main ID: NCT04617925
• Date of registration: 20/10/2020
• Prospective Registration: Yes
• Primary sponsor: Stichting European Myeloma Network
• Public title: A Study of Belantamab Mafodotin in Patients With Relapsed or Refractory AL Amyloidosis EMN27
• Scientific title: A Phase 2 Study of Belantamab Mafodotin in Patients With Relapsed or Refractory AL Amyloidosis
• Date of first enrolment: February 26, 2021
• Target sample size: 35
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT04617925
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

France, Germany, Greece, Italy, Netherlands, United Kingdom

Key inclusion & exclusion criteria

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. Previous systemic therapy for AL amyloidosis

3. Patients must be = 18 years of age.

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:

1. 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).

2. presence of a monoclonal spike that is =0.5 gr/dl.

8. Symptomatic organ involvement (heart, kidney, liver/GI tract, peripheral nervous
system).

9. Patient must have adequate organ function, defined as follows:

System Laboratory Values

Hematologic:

Absolute neutrophil count (ANC) =1.5 X 109/L Hemoglobin =8.0 g/dL Platelets =75 X
109/L

Hepatic:

Total bilirubin =1.5X ULN (Isolated bilirubin =1.5xULN is acceptable if bilirubin is
fractionated and direct bilirubin <35%) ALT =2.5 X ULN Renal: eGFR =30 mL/min/ 1.73
m2 Cardiac:LVEF (Echo) Clinically asymptomatic patients with ECHO confirmed LVEF
=25%

10. Written informed consent in accordance with local and institutional guidelines.

11. 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 breastfeeding,
and at least one of the following conditions applies:

- Is not a woman of childbearing potential (WOCBP) OR

- Is a WOCBP and using a contraceptive method that is highly effective (failure
rate of <1% per year), preferably with low user dependency (as described in
Appendix 3), during the intervention period and for at least four months after
the last dose of study intervention and 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 study intervention.

A WOCBP must have a negative highly-sensitive serum pregnancy test (as required by
local regulations) within 72 hours before the first dose of study intervention.

The investigator is responsible for review of 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):

- =45 years of age and has not had menses for >1 year,

- Patients who have been amenorrhoeic for <2 years without history of a
hysterectomy and oophorectomy must have a follicle stimulating hormone value in
the postmenopausal range upon screening evaluation,

- 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 study treatment to allow
for clearance of any altered sperm:

• Refrain from donating sperm

PLUS either:

• 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

• 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 to
use an additional highly effective contraceptive method with a failure rate of <1%
per year as when having sexual intercourse with a WOCBP who is not currently
pregnant.

13. All prior treatment-related toxicities (defined by National Cancer Institute- Common
Toxicity Criteria for AEs (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. Patients must be able to understand the study procedures and agree to participate in
the study 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.

3. Previously untreated disease: patients must have had at least 2 cycles of therapy
directed against the plasma cell clone; however, patients that have received high
dose therapy with melphalan as their only therapy are eligible for the study.

4. Previous exposure to anti-BMCA agents

5. 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.

6. Known repetitive ventricular arrhythmias on 24h Holter Electrocardiogram (ECG) in
spite of anti-arrhythmic treatment. Patients 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, or
electrocardiographic evidence of acute ischemia or Grade 3 conduction system
abnormalities unless patient has a pacemaker.

- Uncontrolled hypertension or hypotension (i.e., supine SBPN < 90 mmHg despite
supportive therapy with midodrine)

7. Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to
Cycle 1 Day 1.




Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

AL Amyloidosis

Intervention(s)

Drug: Belantamab mafodotin

Primary Outcome(s)

response rate [Time Frame: at 6 months (cycle 4)]

Secondary Outcome(s)

Duration of response [Time Frame: approximately up to 9 years]

Overall hematologic response rates [Time Frame: 3 months, 6 months]

Non-hematologic AEs [Time Frame: up to 70 days after last dose]

Adverse events [Time Frame: up to 70 days after last dose]

Ocular toxicity [Time Frame: up to 1 year]

Dose reduction [Time Frame: up to 1 year]

Organ response rates [Time Frame: 3,6,12,18, and 24 months]

Overall survival [Time Frame: approximately up to 9 years]

Determine time to progression [Time Frame: approximately up to 9 years]

Hematologic AEs [Time Frame: up to 70 days after last dose]

Treatment discontinuation [Time Frame: up to 1 year]

Secondary ID(s)

EMN27

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

GlaxoSmithKline