This is a multicenter phase 2 study of belantamab mafodotin on participants with
plasmablastic lymphoma and ALK+ large B-cell lymphoma.The research study procedures include
screening for eligibility, and study treatment, including evaluations and follow up visits.
- This research study involves the study drug belantamab mafodotin.
- Participants may receive the study treatment until progression or intolerance, and will
be followed up to 2 years.
- It is expected that about 25 people will take part in this research study.
This research study is a Phase II clinical trial. Phase II clinical trials test the safety
and effectiveness of an investigational drug to learn whether the drug works in treating a
specific disease. "Investigational" means that the drug is being studied.
The U.S. Food and Drug Administration (FDA) has not approved belantamab mafodotin as a
treatment for any disease. This study drug is investigational, and it is not known whether
participants will benefit from taking belantamab mafodotin.
- Participants must have relapsed or refractory plasmablastic lymphoma or ALK+ large
Bcell lymphoma by WHO criteria.
- Participants must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter [LDi] to be recorded
for non-nodal lesions and short axis for nodal lesions) as ≥15 mm in LDi for nodal
disease or ≥10 mm in LDi for extranodal lesions.
- Participants must have received prior systemic lymphoma therapy.
- Age ≥18 years. Because no dosing or adverse event data are currently available on the
use of belantamab mafodotin in participants <18 years of age, children are excluded
from this study.
- ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A).
- Participants must have adequate marrow function as defined below (unless abnormalities
are considered related to marrow and/or splenic involvement by lymphoma):
- absolute neutrophil count ≥1,000/mcL
- platelets ≥50,000/mcL
- hemoglobin ≥ 8.0 g/dL
- Participants must have adequate organ function as defined below:
- total bilirubin ≤ 1.5 X institutional upper limit of normal (ULN); (Isolated
bilirubin ≥1.5xULN is acceptable if bilirubin is fractionated and direct
- AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN
- Spot urine (albumin/creatinine) <500 mg/g (56 mg/mmol) OR
- Urine Dipstick Negative/trace (if ≥1+ only eligible if confirmed ≤ 500 mg/g (56
mg/mmol) by albumin/creatinine ratio (spot urine from first void)
- Glomerular filtration rate (eGFR)≥30 mL/min/1.73 m2 (MDRD Formula).
- Participants with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification. To be
eligible for this trial, participants should be class 2B or better.
- Belantamab mafodotin is potentially teratogenic. A female participant is eligible to
participate if she is not pregnant or breastfeeding. Women of child-bearing potential
must agree to use adequate contraception (hormonal or barrier method of birth control;
abstinence) prior to study entry, for the duration of study participation, and for at
least 4 months after the last dose of study intervention. Women must also agree not to
donate eggs (ova, oocytes) for the purpose of reproduction during this period. Should
a woman become pregnant or suspect she is pregnant while she or her partner is
participating in this study, she should inform her treating physician immediately.
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.
- Women of childbearing potential must have a negative highly sensitive serum pregnancy
test, and agree to repeat highly sensitive serum pregnancy testing within 72 hours
before the first dose of study intervention (if screening pregnancy test was not
within 72 hours of dosing).
- Men treated or enrolled on this protocol must also agree to use adequate contraception
prior to the study, for the duration of study participation, and 6 months after
completion of administration. Men must also agree not to donate sperm during this
period. Men may agree to remain abstinent from heterosexual intercourse as their
preferred and usual lifestyle (abstinent on a long term and persistent basis) OR 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 when having sexual intercourse with a WOCBP (including pregnant
- Participants with a prior or concurrent malignancy whose natural history or treatment
does not have the potential to interfere with the safety or efficacy assessment of the
investigational regimen are eligible for this trial at the discretion of the overall
- Ability to understand and the willingness to sign a written informed consent document.
- Participants must not have current corneal epithelial disease except mild changes in
- Participant must not have current unstable liver or biliary disease defined by the
presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, 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
- Participants who have not recovered from adverse events due to prior anti-cancer
therapy (i.e., have residual toxicities > Grade 1) with the exception of alopecia. At
the discretion of the overall PI, participants with residual toxicities > Grade 1 may
be considered eligible if in the opinion of the overall PI the residual toxicity is
not likely to interfere with the safety or efficacy assessment of the investigational
- Participants who are receiving any other investigational agents.
- Participants must not have central nervous system involvement by lymphoma, as
belantamab mafodotin is not known to penetrate the CNS.
- Participant must not use contact lenses while participating in this study.
- Participant must not be simultaneously enrolled in any interventional clinical trial.
- Participant must not have used an investigational drug or approved systemic lymphoma
therapy within 14 days or five half-lives, whichever is shorter, preceding the first
dose of study drug. Steroids are permitted.
- Participant must not have had major surgery within 4 weeks of initiating study
- Participant must not have any evidence of active mucosal or internal bleeding.
- Participants must not have known immediate or delayed hypersensitivity reaction or
idiosyncratic reactions to belantamab mafodotin or drugs chemically related to
belantamab mafodotin, or any of the components of the study treatment.
- Participants must not have an uncontrolled intercurrent illness.
- Participant must not have an uncontrolled active infection.
- Participant must not have evidence of cardiovascular risk including any of the
- 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
angina), coronary angioplasty, or stenting/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].
- Participant must not have uncontrolled hypertension defined as persistent
systolic BP >160 mmHg or diastolic BP >100 mmHg.
- Participant must not have psychiatric illness/social situations that would limit
compliance with study requirements. Participants must not have any serious and/or
pre-existing medical or other condition (including lab abnormalities) that could
interfere with participant's safety in the opinion of the investigator.
- Women who are pregnant or lactating are excluded from this study because belantamab
mafodotin can cause embryo-fetal harm when administered to a pregnant woman. Because
there is an unknown but potential risk for adverse events in nursing infants secondary
to treatment of the mother with belantamab mafodotin, breastfeeding should be
discontinued if the mother is treated with belantamab mafodotin.
- Participant must not have presence of hepatitis B surface antigen (HBsAg), or
hepatitis B core antibody (HBcAb) at screening or within 3 months prior to first dose
of study treatment. Patients with presence of HBsAg, but demonstrate both HBSag and
HBV PCR negativity will be eligible for the study. Participant must not have positive
hepatitis C antibody test result or positive hepatitis C RNA test result at screening
or within 3 months prior to first dose of study treatment. Note: Participants with
positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a
confirmatory negative Hepatitis C RNA test is obtained. Note: Hepatitis RNA testing is
optional and participants with negative Hepatitis C antibody test are not required to
also undergo Hepatitis C RNA testing.
- Participant must not have uncontrolled HIV infection. HIV-infected patients on
effective anti-retroviral therapy are eligible if they (1) have an undetectable viral
load within the prior 6 months, or (2) have a detectable viral load with an absolute
CD4 count of 200 cells per microliter or higher.
- Participant must not have invasive malignancies other than 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 clinical trial treatments on the currently targeted malignancy. Participants with
adequately treated basal, squamous cell carcinoma or non-melanomatous skin cancer,
carcinoma in situ of the cervix, superficial bladder cancer not treated with
intravesical chemotherapy or BCG within 6 months, localized prostate cancer and PSA
<1.0 mg/dL on 2 consecutive measurements at least 3 months apart with the most recent
one being within 4 weeks of study entry, may be enrolled without a 2-year restriction.
- Participant must not have had plasmapheresis within 7 days prior to first dose of
- Participant must not have received prior treatment with a monoclonal antibody within
30 days of receiving the first dose of study drugs