An Open Label Study of JNJ-68284528, Directed Against BCMA in Subjects with Multiple Myeloma
- Conditions
- Multiple MyelomaMedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-004124-10-NL
- Lead Sponsor
- Janssen-Cilag International NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 171
Cohort A:
-1-3 prior lines of therapy, including PI and IMiD
-Lenalidomide refractory
-Anti-CD38 mAb exposure not required
-PD per IMWG criteria =6 months of last regimen; confirmation may be either central or local
-Prior SCT allowed (allo: >6 months before apheresis; auto: >12 weeks before apheresis)
Cohort B:
-Frontline therapy with PI and IMiD
-Transplant and non-transplant patients
-Anti-CD38 mAb exposure not required
-PD per IMWG criteria =12 months of:
a. Autologous SCT
b. Start of initial therapy (non-transplanted patients)
Cohort C:
-Previously treated with PI, IMiD, anti-CD38 mAb and BCMA-directed therapy (as monotherapy or in combination)
a. Irrespective of dose level or response to prior BCMA-directed therapy
-PD per IMWG criteria
a. =12 months of last line of therapy
b. =6 months of prior therapy, and refractory or non-responsive to their most recent line of therapy
Cohort A, B, C:
Measurable disease at Screening as defined by any of the following:
-Serum M-protein =1.0 g/dL or urine M-protein level =200 mg/24 hours; or
-Light chain MM without measurable disease in serum or urine: Serum immunoglobulin free light chain =10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio
-Central screening lab results required for all study patients:
Local laboratory assessments may be used to establish measurable disease at Screening, with local laboratory result =125% of requirements
-For subjects with neither serum nor urine measurable disease, baseline positron emission tomography/ computed tomography (PET/CT) or whole body magnetic resonance imaging (MRI) may be used to satisfy the measurable disease criteria.
-Lab values as defined in the protocol
Cohort D:
-Newly diagnosed MM per IMWG with 4 to 8 total cycles of initial therapy, including induction, high-dose therapy and ASCT with or without consolidation
a. Previously treated for smoldering myeloma not eligible
b. Patient treated with consolidation must have received =2 cycles
- Received IMiD or PI or both in combination with steroid as part of induction or consolidation regimen
-Tx with alkylating therapy (eg, cyclophosphamide) or mAb during induction/ consolidation permitted
-Labs as specified in the protocol
-women of childbearing potential must follow the contraception criteria outlined in the local global REVLIMID® pregnancy prevention program or equivalent local Risk Evaluation and Mitigation Strategy (REMS), whichever is more stringent, as applicable in their region.
-Men should agree to practice contraception according to and for the time frame specified in the local global REVLIMID® pregnancy prevention program or equivalent localREMS, whichever is more stringent, as applicable in their region.
Cohort E:
-Measurable disease at Screening as defined by any of the following:
-Serum M-protein =1.0 g/dL or urine M-protein level =200 mg/24 hours;
or
-Light chain MM without measurable disease in serum or urine: Serum immunoglobulin free light chain =10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio
For participants that have received 1 cycle of anti-myeloma therapy prior to enrollment, measurable disease must be assessed by local laboratory on the most recent evaluation prior to the start of the anti-myeloma therapy.
-Central screening lab results required for all study patients:
Local laboratory assessments may be used to establish measurable disease at Screening, with local laboratory result =125% of requirements
-Not considered candidate
Key Exclusion criteria (All cohorts):
-Antitumor treatment washout prior to apheresis
-Toxicity from previous anticancer therapy must have resolved to baseline or =Grade 1 except alopecia or peripheral neuropathy
- Serious underlying medical condition, eg:
a.Clinically significant cardiac conditions (CHF, MI, LVEF <45%)
b. Active / Hx of autoimmune disease within 3 yrs
c. Dementia or altered mental status
d. Serious viral, bacterial or uncontrolled systemic fungal infection
e. Seropositive for HIV
f. Clinically significant Hepatitis B or C infection
- Cumulative dose of corticosteroids equivalent to =70 mg of prednisone =7 days prior to apheresis
- Stroke or seizure =6 months
- Pregnant, breast-feeding or planning to become pregnant / father child while enrolled in study and until 1 year after receiving a JNJ-68284528 infusion
- Contraindications, known life threatening allergies, hypersensitivity, or intolerance to cyclophosphamide, fludarabine, or JNJ-68284528 or its excipients, including DMSO (refer to Investigator’s Brochure).
Cohort D:
-Pregnant or breast-feeding, or planning to become pregnant while enrolled in this study and until 1 year after receiving a JNJ-68284528 infusion or for 4 weeks following discontinuation of lenalidomide (whichever is later).
-Contraindications, known life threatening allergies, hypersensitivity, or intolerance to cyclophosphamide, fludarabine, lenalidomide, or JNJ-68284528 or its
excipients, including DMSO (refer to Investigator’s Brochure).
Cohort E:
Contraindications, known life threatening allergies, hypersensitivity, or intolerance to boron or mannitol, hyaluronidase, sorbitol, corticosteroids, monoclonal antibodies or human proteins, cyclophosphamide, fludarabine, lenalidomide, daratumumab,
bortezomib, dexamethasone, or JNJ-68284528 excipients, including DMSO.
-Pregnant or breast-feeding, or planning to become pregnant while enrolled in this study and until: 1 year after receiving a JNJ-68284528 infusion, or for 4 weeks
following discontinuation of lenalidomide, or until 3 months after daratumumab (whichever is later).
-Plans to father a child while enrolled in this study until: 1 year after receiving a JNJ-68284528 infusion, or for 4 weeks following discontinuation of lenalidomide, or until 3 months after daratumumab (whichever is later).
Cohort F:
- Active malignancies (ie, progressing or requiring treatment change in the last 24 months) other than the disease being treated under study.
- Prior therapy, prior to apheresis
- Received a cumulative dose of corticosteroids equivalent to =70 mg of prednisone within the 7 days prior to apheresis
- Ongoing toxicity from previous anticancer therapy must have resolved to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy.
- Major surgery within 2 weeks prior to apheresis, or surgery planned after apheresis up to 2 weeks after cilta-cel administration.
For a full list of exclusion criteria, please refer to the protocol
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method