CRISPR Delivered Anti-BCMA Car-T Therapy for Relapsed or Refractory Multiple Myeloma
A Phase 1b Clinical Trial of CRISPR Delivered Anti-BCMA Chimeric Antigen Receptor T Cells for Treatment of Relapsed or Refractory Multiple Myeloma
2 other identifiers
interventional
30
1 country
1
Brief Summary
This phase Ib trial tests the safety, side effects and best dose of clustered regularly interspaced short palindromic repeats (CRISPR) delivered anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR)-T cells (1XX BCMA CAR-T cells) in treating patients with multiple myeloma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Anti-BCMA CAR-T cell therapy is a type of treatment in which a person's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein, such as BCMA, on the patient's cancer cells is added to the T cells in the laboratory by a tool called clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9. The special receptor is called a CAR. Large numbers of the CAR-T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Giving chemotherapy before CAR-T cells may decrease the number of lymphocytes (a type of white blood cells) in the blood and may help the 1XX BCMA CAR-T cells fight the cancer cells. Treatment with 1XX BCMA CAR-T cells may be safe, tolerable, and/or effective in treating patients with relapsed or refractory multiple myeloma (RRMM).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1 multiple-myeloma
Started Feb 2026
Longer than P75 for phase_1 multiple-myeloma
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 5, 2026
CompletedFirst Posted
Study publicly available on registry
January 14, 2026
CompletedStudy Start
First participant enrolled
February 28, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 25, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
May 25, 2043
March 10, 2026
March 1, 2026
2.2 years
January 5, 2026
March 7, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (5)
Proportion of participants with treatment-emergent adverse events
Proportion of participants with treatment-emergent adverse events of CAR-T in RRMM as graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 5.0), revised Cytokine Release Syndrome (CRS) grading criteria (for CRS grading), and the American Society for Transplantation and Cell Transplantation (ASTCT) Immune effector cell-associated neurotoxicity syndrome (ICANS) Consensus Grading for Adults (for neurotoxicity grading).
Up to 12 months following CAR-T infusion
Proportion of participants who experience dose-limiting toxicity (DLT) (Dose Escalation)
The DLT evaluable analysis set includes all participants in the dose-finding part of the study who have received the target doses of anti-BCMA CAR-T cell product, and who have either experienced a DLT or were followed for the full DLT evaluation period. The trial observation period for dose limiting toxicities will conclude at day 30 (approximately 4 weeks after CAR-T cell infusion)
Up to 30 days
Maximum Tolerated Dose (MTD) (Dose Escalation)
The DLT evaluable analysis set includes all participants in the dose-finding part of the study who have received the target doses of anti-BCMA CAR-T cell product, and who have either experienced a DLT or were followed for the full DLT evaluation period (within 28 days following infusion of CAR-T cells targeting BCMA). The MTD is defined as the dose level immediately below that in which ≥ 2/6 participants experience a DLT.
Up to 28 days
Best Overall Response Rate (BORR) (Dose expansion + MTD dose escalation cohort)
ORR is defined as the proportion of participants with stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), as per International Myeloma Working Group (IMWG) criteria, as best overall response over the total population. ORR will be reported as proportion with 90% binomial confidence interval for the expansion cohort including the patients on MTD in the dose escalation cohort(s).
Up to 12 months following CAR-T infusion
Proportion of participants with of severe neurologic events (Dose Expansion)
Incidence of severe neurologic events defined as grade 2 or higher will be reported as a proportion of the total participants by group.
From initiation of study treatment to 12 months following CAR-T infusion, approximately 13 months total
Secondary Outcomes (9)
Overall Response Rate (ORR) - Long term
Up to 15 years
Median Duration of Response (DoR) - Beginning of response
Up to 15 years
Median Progression-free Survival from Study Entry (PFS-SE)
up to 15 years
Median DoR - First documented response
up to 15 years
Median Overall Survival (OS)
up to 15 years
- +4 more secondary outcomes
Study Arms (3)
Dose Escalation Starting Dose: 10 × 10^6 CAR + T cells/ infusion
EXPERIMENTALParticipants undergo leukapheresis and then receive lymphodepleting chemotherapy with fludarabine IV over 30 minutes and cyclophosphamide IV over 60 minutes on days -5, -4, and -3. Participants also receive 10 × 10\^6 BCMA CAR-T cells/ infusion over 5-30 minutes on day 1 in the absence of disease progression or unacceptable toxicity. Additionally, participants undergo PET/CT or MRI at screening and urine and blood sample collection, bone marrow biopsy or aspiration throughout the study.
Dose Escalation: Planned Dose: 30 × 10^6 CAR + T cells/ infusion
EXPERIMENTALDependent on the safety profile of the starting dose, participants undergo leukapheresis and then receive lymphodepleting chemotherapy with fludarabine IV over 30 minutes and cyclophosphamide IV over 60 minutes on days -5, -4, and -3. Participants also receive 30 × 10\^6 BCMA CAR-T cells/ infusion over 5-30 minutes on day 1 in the absence of disease progression or unacceptable toxicity. Additionally, participants undergo PET/CT or MRI at screening and urine and blood sample collection, bone marrow biopsy or aspiration throughout the study.
Expansion: MTD of Anti-BCMA CAR-T
EXPERIMENTALParticipants undergo leukapheresis and then receive lymphodepleting chemotherapy with fludarabine IV over 30 minutes and cyclophosphamide IV over 60 minutes on days -5, -4, and -3. Participants also receive the MTD of BCMA CAR-T cells/ infusion established in the dose escalation phase over 5-30 minutes on day 1 in the absence of disease progression or unacceptable toxicity. Additionally, participants undergo PET/CT or MRI at screening and urine and blood sample collection, bone marrow biopsy or aspiration throughout the study.
Interventions
Given Intravenously (IV)
Ancillary studies
Undergo biopsy
Undergo Blood, serum and urine collection
Given IV
Undergo radiographic imaging
Undergo Leukapheresis
Given Intravenously (IV)
Eligibility Criteria
You may qualify if:
- Voluntarily sign informed consent form.
- Age ≥18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
- Diagnosis of multiple myeloma (per IMWG criteria) with relapsed or refractory disease and has received at least 3 prior lines of therapy including proteasome inhibitor immunomodulatory therapy, and anti-Cluster of differentiation 38 (CD38) antibody therapy.
- Participants may have received BCMA targeted therapy and must be at least 6 months from last BCMA therapy.
- Participants must have documented evidence of progressive disease within 12 months of the last line of therapy or be refractory/nonresponsive to their most recent line.
- Participants must have measurable disease, defined as at least one of the criteria below:
- Serum M-protein greater or equal to 0.5 grams per deciliter (g/dL).
- Urine M-protein greater or equal to 200 milligrams, over a 24-hour period (mg/24 h).
- Serum free light chain (FLC) assay: involved FLC level of ≥ 100 milligrams per liter (mg/L).
- Adequate organ function, defined as:
- Adequate bone marrow function for apheresis and lymphodepleting chemotherapy.
- Hgb \>8 gm/dl (transfusions allowed).
- Platelets \>50,000/microliter (uL) (in the absence of platelet transfusion within 7 days of apheresis, but transfusion permitted prior to lymphodepleting chemotherapy).
- Absolute neutrophil count (ANC) \> 1000/uL in the absence of growth factor support (filgrastim within 7 days or pegfilgrastim within 14 days of apheresis, but growth factor permitted prior to lymphodepleting chemotherapy). For those patients who have evidence of duffy null, ANC \>750/uL is allowed.
- +6 more criteria
You may not qualify if:
- Autologous transplant within 12 weeks of planned CAR-T cell infusion.
- Prior antitumor therapy as follows, prior to apheresis:
- Investigational therapy within 14 days, or at least 5 half-lives.
- Monoclonal antibody therapy within 21 days.
- Cytotoxic therapy within 14 days.
- Proteasome inhibitor therapy within 14 days.
- Immunomodulatory therapy within 14 days.
- Radiotherapy within 14 days - with the exception that if radiotherapy (XRT) covers \<5% of marrow reserve - no rest window needed.
- Active CNS multiple myeloma, plasma cell leukemia, primary AL amyloidosis or POEMS syndrome.
- Active other malignancy, other than non-melanoma skin cancer, carcinoma in situ (e.g., cervix, bladder, or breast). Any fully treated malignancies or indolent, clinically insignificant malignancies can be discussed among the study team to determine eligibility.
- HIV seropositivity.
- Serologic status reflects active hepatitis B or C infection. Participants that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive participants will be excluded).
- Participants with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, pulmonary abnormalities, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant or breastfeeding women are excluded from this study because CAR-T cell therapy may be associated with the potential for teratogenic or abortifacient effects. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with CAR-T cells, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study.
- NOTE: Women of childbearing potential must have a negative serum or urine pregnancy test.
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University of California, San Francisco
San Francisco, California, 94143, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Thomas G Martin, MD
University of California, San Francisco
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
January 5, 2026
First Posted
January 14, 2026
Study Start
February 28, 2026
Primary Completion (Estimated)
May 25, 2028
Study Completion (Estimated)
May 25, 2043
Last Updated
March 10, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will not share