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 BCell 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-IT
- Lead Sponsor
- MERCK SHARP & DOHME CORP. UNA SUSSIDIARIA DI MERCK & CO. INC.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 100
1. Has relapsed or refractory DLBCL and have failed at least 2 lines of prior therapy, and have failed auto-SCT or are auto-SCT ineligible. Must have received prior rituximab/anti-CD20 monoclonal antibody.
a Relapsed disease: progression after achieving an overall response of PR or CR in response to the most recent therapy.
b Refractory disease: failure to achieve CR or PR to the most recent therapy.
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. Histologically confirmed diagnosis of DLBCL, according to the WHO classification of neoplasms of the hematopoietic and lymphoid tissues.
3. a. Has radiographically measurable DLBCL per the Lugano Response Criteria, with at least 1 nodal lesion (non-irradiated) 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. Life expectancy of at least 3 months, in the opinion of the investigator.
5. Is male or female, from 18 years of age inclusive, at the time of signing the informed consent.
6. 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 as detailed below:
- Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant.
• Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed.
7. A female participant is eligible to participate if she is 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 be 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 and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period. 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 method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention.
-Contraceptive use by women should be consistent with local regulations regarding the me
1. 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. Has received prior therapy with a ROR1-directed therapy.
10. Has contraindication to any of the study intervention components.
11. Transformed DLBCL from indolent lymphoma.
12. 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 treatment for their GVHD.
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 4 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (<=2 weeks of radiotherapy) to non-CNS disease.
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.
For more exclusion criteria please see the protocol.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate zilovertamab vedotin with respect to objective response rate per Lugano Response Criteria as assessed by BICR;Secondary Objective: 1. To evaluate zilovertamab vedotin with respect to duration of response per Lugano Response Criteria as assessed by BICR<br>2. To evaluate zilovertamab vedotin with respect to progression-free survival per Lugano Response Criteria as assessed by BICR<br>3. To evaluate zilovertamab vedotin with respect to overall survival<br>4. To evaluate the safety and tolerability of zilovertamab vedotin;Primary end point(s): Objective Response Rate (ORR);Timepoint(s) of evaluation of this end point: Up to approximately 17 months
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1. Duration of Response (DOR)<br>2. Progression-free Survival (PFS)<br>3. Overall Survival (OS)<br>4. Number of Participants Who Experience an Adverse Event (AE)<br>5. Number of Participants Who Discontinue Study Treatment Due to an AE;Timepoint(s) of evaluation of this end point: 1. Up to approximately 72 months<br>2. Up to approximately 72 months<br>3. Up to approximately 72 months<br>4. Up to approximately 14 months<br>5. Up to approximately 11 months