CRISPR Delivered Anti-BCMA Car-T Therapy for Relapsed or Refractory Multiple Myeloma
NCT ID: NCT07340853
Last Updated: 2026-01-14
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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NOT_YET_RECRUITING
PHASE1
30 participants
INTERVENTIONAL
2026-02-28
2043-05-25
Brief Summary
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Detailed Description
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Dose Escalation:
I. To evaluate the safety and toxicity of administering Chimeric Antigen Receptor T Cells (CAR-T) cells targeting BCMA to participants with Relapsed or Refractory Multiple Myeloma (RRMM).
II. To determine the maximum tolerated dose (MTD) for anti-BCMA CAR-T cells.
Dose Expansion:
III. Determine whether administering conforming CAR T-cell product targeting BCMA to participants with RRMM increases the overall response rate (ORR) compared with historical data for non-CAR agents per International Myeloma Working Group (IMWG) response criteria.
IV. Determine whether administering conforming CAR T-cell product targeting BCMA to participants with RRMM lowers the Grade 2 or greater neurologic events to \<10% in RRMM.
SECONDARY OBJECTIVES:
Dose Expansion:
I. To describe the efficacy of conforming CAR-T cell product targeting BCMA in participants with RRMM.
II. To evaluate the feasibility of manufacturing anti-BCMA CAR T-cells locally and ability to produce adequate quantities of vector positive T-cells.
III. To evaluate the safety and toxicity of conforming CAR-T cell product targeting BCMA to participants with RRMM.
EXPLORATORY OBJECTIVES:
I. To determine the degree and impact of CAR-T persistence following anti-BCMA CAR-T cell infusion, on clinical outcomes and safety.
II. Describe changes in health-related quality of life (HRQoL) using the European Organization for Research and Treatment of Cancer - Quality of Life C30 questionnaire (EORTC-QLQ-C30).
III. To describe the efficacy of CAR-T cells targeting BCMA in participants with relapsed or refractory BCMA+ RRMM who were treated with product that did not meet one or more pre-specified release criteria (non-conforming product cohort).
OUTLINE:
Participants in both cohorts will undergo leukapheresis, receive lymphodepleting chemotherapy and then receive a single infusion of BCMA CAR-T therapy. After completion of study treatment, participants are followed up at 30, 60 and 90 days, 6 and 12 months, and then yearly for up to 15 years.
Conditions
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Study Design
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NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
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Dose Escalation Starting Dose: 10 × 10^6 CAR + T cells/ infusion
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 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.
Leukapheresis
Undergo Leukapheresis
Cyclophosphamide
Given Intravenously (IV)
Chimeric Antigen Receptor T cells (CAR-T) Targeting BCMA
Given Intravenously (IV)
Quality of Life (QoL) Questionnaires
Ancillary studies
Bone Marrow Biopsy
Undergo biopsy
Biospecimen Collection
Undergo Blood, serum and urine collection
Fludarabine
Given IV
Radiographic imaging
Undergo radiographic imaging
Dose Escalation: Planned Dose: 30 × 10^6 CAR + T cells/ infusion
Dependent 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.
Leukapheresis
Undergo Leukapheresis
Cyclophosphamide
Given Intravenously (IV)
Chimeric Antigen Receptor T cells (CAR-T) Targeting BCMA
Given Intravenously (IV)
Quality of Life (QoL) Questionnaires
Ancillary studies
Bone Marrow Biopsy
Undergo biopsy
Biospecimen Collection
Undergo Blood, serum and urine collection
Fludarabine
Given IV
Radiographic imaging
Undergo radiographic imaging
Expansion: MTD of Anti-BCMA CAR-T
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 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.
Leukapheresis
Undergo Leukapheresis
Cyclophosphamide
Given Intravenously (IV)
Chimeric Antigen Receptor T cells (CAR-T) Targeting BCMA
Given Intravenously (IV)
Quality of Life (QoL) Questionnaires
Ancillary studies
Bone Marrow Biopsy
Undergo biopsy
Biospecimen Collection
Undergo Blood, serum and urine collection
Fludarabine
Given IV
Radiographic imaging
Undergo radiographic imaging
Interventions
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Leukapheresis
Undergo Leukapheresis
Cyclophosphamide
Given Intravenously (IV)
Chimeric Antigen Receptor T cells (CAR-T) Targeting BCMA
Given Intravenously (IV)
Quality of Life (QoL) Questionnaires
Ancillary studies
Bone Marrow Biopsy
Undergo biopsy
Biospecimen Collection
Undergo Blood, serum and urine collection
Fludarabine
Given IV
Radiographic imaging
Undergo radiographic imaging
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Age ≥18 years.
3. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
4. 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.
5. Participants may have received BCMA targeted therapy and must be at least 6 months from last BCMA therapy.
6. 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.
7. 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).
8. 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.
* Absolute lymphocyte count (ALC) \>300/uL.
* Alanine aminotransferase/aspartate aminotransferase (ALT/AST) \< 3 x institutional upper limit of normal (ULN) and Total bilirubin \< 1.5 milligrams per deciliter (mg/dl) x institutional ULN, except with Gilbert's syndrome.
* Serum creatinine clearance (CrCl) ≥ 30 milliliter per minute (mL/min) using Cockcroft-Gault formula or as measured with a 24 hour urine collection.
* Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) \> 40% as assessed by echocardiogram or multiple uptake gated acquisition (MUGA) and adequate pulmonary function (measured by room air pulse oximetry ≥ 92%).
9. Women of childbearing potential must have a negative serum or urine pregnancy test AND agree to use highly effective methods of contraception for 1 year after the last dose of anti-BCMA CAR-T cells.
10. Males who have partners of childbearing potential must agree to use an effective barrier contraceptive method for 6 months after CAR-T therapy.
Exclusion Criteria
2. 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.
3. Toxicity from previous anticancer therapy must resolve to baseline levels or to Grade 1 or less except for alopecia, peripheral neuropathy and baseline hematologic toxicity that otherwise meets inclusion.
4. Active CNS multiple myeloma, plasma cell leukemia, primary AL amyloidosis or POEMS syndrome.
5. 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.
6. HIV seropositivity.
7. 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).
8. 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.
9. 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.
10. Participants with currently symptomatic central nervous system (CNS) pathology such as epilepsy, seizure disorders, paresis, aphasia, uncontrolled cerebrovascular disease, severe brain injuries, dementia, and Parkinson's disease OR seizure or stroke within 6 months.
11. History of autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus) with requirement of immunosuppressive medication within 6 months.
18 Years
ALL
No
Sponsors
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Thomas Martin, MD
OTHER
Responsible Party
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Thomas Martin, MD
Principal Investigator
Principal Investigators
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Thomas G Martin, MD
Role: PRINCIPAL_INVESTIGATOR
University of California, San Francisco
Locations
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University of California, San Francisco
San Francisco, California, United States
Countries
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Central Contacts
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Facility Contacts
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Role: backup
Other Identifiers
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NCI-2025-08425
Identifier Type: REGISTRY
Identifier Source: secondary_id
25707
Identifier Type: -
Identifier Source: org_study_id
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