A Research Study, where the participant and healthcare providers are aware of the treatment being given, to evaluate safety and effectiveness of medication MK-2140 in patients with Diffuse Large B Cell Lymphoma who failed prior therapies.
- Conditions
- Treatment of participants with Relapsed or Refractory Diffuse Large B-Cell LymphomaMedDRA version: 21.0Level: PTClassification code 10012818Term: Diffuse large B-cell lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2021-003397-32-PL
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 100
1. Has relapsed or refractory DLBCL, has progressed after at least 2 lines
of prior therapy, and has progressed after auto-SCT or is auto-SCT
ineligible. Must have received prior multiagent regimen that includes an
alkylating agent, anthracycline, and anti-CD20 monoclonal antibody
a Relapsed disease: progression (Lugano Response Criteria) =6 months
from completion of the most recent therapy after achieving an overall
response of PR or CR
b Refractory disease: failure to achieve CR or PR to the most recent
therapy OR disease progression (Lugano Response Criteria) <6 months
from completion of the most recent therapy after achieving an overall
response of PR or CR
c Ineligibility for auto-SCT:
Is >65 years old
Has organ dysfunction or comorbidities precluding the use of HDT or auto-SCT
Has not responded to salvage therapy
Has refused auto-SCT
Has an inability to successfully collect peripheral blood stem cells
2. Histologically confirmed diagnosis of DLBCL, according to the WHO
classification of neoplasms of the hematopoietic and lymphoid tissues,
including: DLBCL, NOS, germinal center B-cell type, or activated B-cell
type; DLBCL leg-type; EBV+ DLBCL, NOS; and T cell histiocytic-rich
DLBCL DLBCL with overexpression of MYC, BCL2, and/or BCL6 proteins
without rearrangement are also classified as DLBCL. DLBCL (HGBL) with
MYC, BCL2, and/or BCL6 rearrangement will also be included
3. a. Has radiographically measurable DLBCL per the Lugano Response
Criteria, with at least 1 nodal lesion (nonirradiated) that is >1.5 cm in
the long axis, regardless of length of the short axis, AND/OR extranodal
lesion of =1.0 cm in the long and short axis and
b. Has PET positive disease verified by BICR at Screening defined as 4-5
on a 5-point scale
4. Has progressed after CAR-T therapy or is ineligible for CAR-T cell
therapy
5. Life expectancy of at least 3 months, in the opinion of the investigator
6. Is male or female, from 18 years of age inclusive, at the time of
providing the informed consent
7. Male participants are eligible to participate if they agree to the
following during the intervention period and for at least the time needed
to eliminate each study intervention after the last dose of study
intervention. The length of time required to continue contraception for
each study intervention is:
• Zilovertamab vedotin: 110 days
• Refrain from donating sperm
PLUS either:
• Be abstinent from heterosexual intercourse as their preferred and
usual lifestyle and agree to remain abstinent
OR
• Must agree to use contraception unless confirmed to be azoospermic
• Contraceptive use by men should be consistent with local regulations
8. A female participant is eligible to participate if not pregnant or
breastfeeding, and at least one of the following conditions applies:
• Is not a WOCBP
OR
• Is a WOCBP and:
- Uses a contraceptive method that is highly effective, with low user
dependency, or is abstinent from heterosexual intercourse as their
preferred and usual lifestyle (abstinent on a long-term and persistent
basis), during the intervention period and for at least the time needed to
eliminate each study intervention after the last dose of study
intervention. The participant agrees not to donate eggs (ova, oocytes) to
others or freeze/store for the purpose of reproduction. The length of
time required to continue contraception for each study intervention is as
follows:
? Zilovertamab Vedotin 50 days
The investigator should evaluate the potential for contraceptive met
Has received a diagnosis of PMBCL.
2. Has undergone solid organ transplant at any time.
3. Has clinically significant (ie, active) cardiovascular disease: cerebral
vascular accident/stroke (<6 months prior to enrollment), myocardial
infarction (<6 months prior to enrollment), unstable angina, congestive
heart failure (New York Heart Association Classification Class = II),
serious cardiac arrhythmia requiring medication, arterial
thromboembolism, cerebrovascular thromboembolism (<6 months prior
to enrollment), uncontrolled Grade =3 hypertension (diastolic blood
pressure =100 mm Hg or systolic blood pressure =160 mm Hg) despite
antihypertensive therapy; or significant conduction system ECG
abnormalities, including second-degree AV block type II, third-degree
AV block, or Grade =2 bradycardia, or serious cardiac arrhythmia
requiring medication.
4. Known history of liver cirrhosis.
5. Has pericardial effusion or clinically significant pleural effusion.
6. Has baseline peripheral neuropathy> Grade 1.
7. Has a history of a second malignancy, unless potentially curative
treatment has been completed with no evidence of malignancy for 2
years.
8. Has a demyelinating form of Charcot-Marie-Tooth disease.
9. Transformed DLBCL from indolent lymphoma.
10. In participants with prior allo-SCT, acute GVHD or ongoing evidence
of chronic GVHD manifesting as Grade =2 serum bilirubin, Grade =3 skin
involvement, or Grade =3 diarrhea or requiring systemic
immunosuppression for treatment/prophylaxis for their GVHD.
11. Has received prior therapy with a ROR1-directed therapy.
12. Has contraindication to any of the study intervention components.
13. Has received prior systemic anticancer therapy, including
investigational agents within 4 weeks prior to the first dose of study
intervention.
14. Has received prior radiotherapy within 28 days of start of study
intervention. Participants must have recovered from all radiation-related
toxicities.
15. Has ongoing corticosteroid therapy (exceeding 30 mg daily of
prednisone equivalent). Prednisone equivalent dosing must have been
stable for at least 4 weeks prior to C1D1.
16. Has received a live or live-attenuated vaccine within 30 days before
the first dose of study intervention. Administration of killed vaccines are
allowed.
17. Has received a strong inhibitor or inducer of CYP3A4 (including
itraconazole, ketoconazole, posaconazole, or voriconazole) within 7 days
prior to C1D1 or expected requirement for chronic use of a strong
CYP3A4 inhibitor or inducer during the study intervention period and for
30 days after the last dose of study intervention.
18. Is currently participating in or has participated in a study of an
investigational agent or has used an investigational device within 4
weeks before the first dose of study intervention.
19. Has known active CNS lymphoma involvement or active CNS
involvement by lymphoma. Participants with prior CNS involvement are
eligible if their CNS disease is in radiographic, cytological (for
cerebrospinal fluid disease), and clinical remission.
20. Has an active infection requiring systemic therapy.
21. Has a known history of HIV infection. No HIV testing is required
unless mandated by local health authority.
22. Has a known history of hepatitis B (defined as HBsAg reactive) or
known active hepatitis C virus (defined as HCV RNA [qualitative] is
detected) infection.
23. Has a history or current evidence of any condition, therapy, or
laboratory abnormality that might confound the r
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: 1. To evaluate zilovertamab vedotin with respect to objective response<br>rate per Lugano Response Criteria as assessed by Blinded Independent<br>Central Review (BICR);Secondary Objective: 1. To evaluate zilovertamab vedotin with respect to duration of response<br>per Lugano Response Criteria as assessed by BICR<br>2. To evaluate the safety and tolerability of zilovertamab vedotin<br>;Primary end point(s): 1. Objective Response Rate (ORR) per Lugano Response Criteria;Timepoint(s) of evaluation of this end point: Up to approximately 3.5 years
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1. Duration of Response (DOR) per Lugano Response Criteria<br>2. Number of Participants Who Experience an Adverse Event (AE)<br>3. Number of Participants Who Discontinue Study Treatment Due to an<br>AE<br>;Timepoint(s) of evaluation of this end point: 1. Up to approximately 3.5 years<br>2. Up to approximately 3.5 years<br>3. Up to approximately 3.5 years