Study of CART-ddBMCA in Relapsed or Refractory Multiple Myeloma
Study Details
Study Description
Brief Summary
A Phase II study of CART-ddBCMA for patients with relapsed or refractory multiple myeloma. CART-ddBCMA is a BCMA-directed CAR-T cell therapy.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
CART-ddBCMA uses a novel extracellular binding domain (ddBCMA) to engage BCMA on myeloma cells and affect tumor kill through activation of 4-1BB and CD3ξ intracellular cascades within T cells. The study will be comprised to include patients with relapsed or refractory multiple myeloma who are 18 years of age or older and meet IMWG criteria for disease assessment
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: CART-ddBCMA one time dose of CART-ddBMCA administered by IV infusion |
Biological: CART-ddBCMA
BCMA-directed CAR T-cell therapy using d domain
|
Outcome Measures
Primary Outcome Measures
- Subject Response Rate (Overall Response Rate) [24 months]
Independent review committee will review results from blood, bone marrow, urine samples and, if applicable, radiographical assessments to determine overall response rate (ORR) per International Myeloma Working Group (IMWG) criteria (Kumar 2016).
Secondary Outcome Measures
- Stringent Complete Response (sCR) or Complete Response (CR) Rate [24 months]
Number of subjects who have a best response of stringent complete response (sCR) or complete response (CR) by IMWG criteria.
- Length of Disease Response [24 months]
For all subjects, the amount of time (e.g., days or months) from the date of first response achieved by IMWG criteria until the date at which progression or death occurs to determine duration of response (DoR).
- Very Good Partial Response (VGPR) or Partial Response (PR) Rate [24 months]
Number of subjects who achieve an overall best response of VGPR or PR as determined by IMWG criteria
- Length of Time to First Disease Response [24 months]
The amount of time (e.g., days or months) from the date of infusion of CART-ddBCMA to the date upon which the first disease response of PR or better occurs by IMWG criteria.
- Progression Free Survival (PFS) and Overall Survival (OS) [24 months]
Time (e.g., days or months) from the date of infusion to the date upon which progression of disease is determined by IMWG criteria or death by any cause occurs.
- Minimal Residual Disease (MRD) [24 months]
Number of subjects that are MRD negative (i.e., no measurable tumor cells in at least 105 cells isolated from the bone marrow) by central laboratory assessment and how this correlates to sCR/CR rates, duration of response and progression free survival.
- Adverse Event Collection [24 months]
Using CTCAE version 5.0, review the number of adverse events that occur for all sujbects including adverse events of special interest (AESIs) and serious adverse events (SAEs).
- Pharmacokinetics of CART-ddBCMA [24 months]
Collect blood samples to isolate and analyze the number of peripheral blood mononuclear cells by vector copy number (VCN) at defined timepoints
- Anti-CART-ddBCMA antibodies [24 months]
Analyze blood serum samples to determine the proportion of subjects who develop antibodies against CART-ddBCMA and the timing and titer of antibodies developed
- Health Related Qualify of Life (HRQoL) [24 months]
Data collected by self assessment using validated questionnaires to compare total scores reported in pre versus post treatment and at specified timepoints.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Age 18 years of age or older and has capacity to give informed consent
-
Relapsed or refractory Multiple Myeloma treated with at least 3 prior regimens of systemic therapy including proteasome inhibitor, IMiDs and anti-CD38 antibody and are refractory to the last line of therapy. For each line, 2 consecutive cycles are required unless the best response after 1 cycle was progressive disease.
-
Documented measurable disease including at least one or more of the following criteria:
-
serum m-protein ≥ 1.0 g/dL
-
urine m-protein ≥ 200 mg/24 hours
-
involved serum free light chain ≥ 10 mg/dL with abnormal kappa/lambda ratio (> 4:1 or < 1:2)
-
ECOG performance status 0-1
-
life expectancy > 12 weeks
-
adequate organ function as defined
-
resolution of AEs prior therapies to Gr 1 or baseline
-
if child bearing potential, must agree to highly effective means of birth control
-
willing to comply with the protocol and up to 15 years long term safety follow-up
-
leukapheresis product can be collected and accepted by manufacturing site.
Exclusion Criteria:
-
plasma cell leukemia or history of plasma cell leukemia
-
treatment with the following therapies:
-
prior systemic treatment for MM within the last 14 days prior to leukapheresis
-
receiving high dose systemic steroid therapy
-
prior treatment with any gene therapy or gene-modified cellular therapy
-
prior BCMA directed therapy
-
autologous stem cell transplant within 3 months prior to leukapheresis
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patients with solitary plasmacytomas without evidence of other measurable disease are excluded.
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history of allergy or sensitivity to study drug components (prior history of reaction to DMSO)
-
contraindication to fludarabine or cyclophosphamide
-
severe or uncontrolled intercurrent illness or lab abnormality
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seropositive for and with evidence of active Hepatitis B or C infection at time of screening or HIV seropositive
-
active CNS involvement by malignancy
-
any sign of active or prior CNS pathology
-
active malignancy not related to myeloma that has required therapy in the last 3 years or is not in complete remission.
-
females who are pregnant or breastfeeding or child bearing potential not willing to agree to effective method of birth control.
-
significant medical condition, laboratory abnormality or psychiatric illness that would prevent participation.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
| 2 | Medical College of Wisconsin | Milwaukee | Wisconsin | United States | 53226 |
Sponsors and Collaborators
- Arcellx, Inc.
- Multiple Myeloma Research Foundation
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ARC-112A