Relapsed/Refractory Multiple Myeloma (RRMM)Phase 1NCT07874334
Phase 1a/b Study of GPRC5D CART Therapy in Relapsed/Refractory Multiple Myeloma and Light-chain Amyloidosis
A Phase 1 study testing GPRC5D CART in people with Relapsed/Refractory Multiple Myeloma (RRMM) and Light-Chain Amyloidosis, run by Hadassah Medical Organization at 1 site in Israel.
Trial summary
A Phase 1a/b Open-Label Study to Evaluate Safety and Preliminary Efficacy of GPRC5D CART Therapy for the Treatment of Relapsed/Refractory Multiple Myeloma and Light-chain Amyloidosis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed/Refractory Multiple Myeloma (RRMM), Light-Chain Amyloidosis
- What is being tested?
- GPRC5D CART
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 160 participants
- Where
- 1 siteIsrael
- Study dates
- 1 Nov 2026to 31 Dec 2032
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥18 years of age at the time of signing informed consent.
- Voluntarily signed informed consent form.
- Diagnosis of relapsed/refractory multiple myeloma or AL amyloidosis, with measurable disease at screening visit as follows:
- Multiple Myeloma (at least one of the criteria below):
- Serum M-protein greater or equal to 0.5 g/dL.
- Positive test for urine M-protein.
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- Serum free light chain (FLC) assay: involved FLC level greater or equal to 3 mg/dL (30 mg/L) provided serum FLC ratio is abnormal.
- A biopsy- or PET-CT- proven evaluable plasmacytoma*.
- Bone marrow plasma cells > 10% of total bone marrow cells*.
- Non secretory patient will be allowed provided they have measurable disease by PET-CT or MRI or bone marrow aspiration, as designated*.
- Results pre-dating the Screening visit by up to 28 days may be used to establish eligibility AL Amyloidosis Serum free light chain (FLC) assay: involved FLC level greater or equal to 3 mg/dL (30 mg/L) provided serum FLC ratio is abnormal.
- Prior Exposure:
- Multiple Myeloma: Subject must have been exposed to at least 3 prior lines of therapy including the following agents:
- proteasome inhibitor
- immunomodulatory (IMiDs) drug
- anti-CD38 antibody
- AL Amyloidosis: Subject have been exposed to 2 prior lines of therapy which include/s the following agents:
- proteasome inhibitor
- anti-CD38 antibody
- Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2.
- Women of child-bearing potential (WCBP), defined as a sexually mature woman who has not undergone a hysterectomy or tubal ligation or who has not been naturally postmenopausal for at least 24 consecutive months, must have a negative serum pregnancy test prior to treatment. All sexually active WCBP and all sexually active male subjects must agree to use effective methods of birth control throughout the study.
- Recovery to ≤ Grade 2 or baseline of any non-hematologic toxicities due to prior treatments, excluding alopecia and Grade 3 neuropathy.
- Ability and willingness to adhere to the study visit schedule and all protocol requirements.
- Subjects who have previously undergone allogenic stem cell transplantation are without evidence of graft versus host disease after cessation of any immunosuppressive therapy for at least one month before recruitment to the study.
- Subjects with Absolute Lymphocyte Count (ALC) > 0.3 × 109/L
Who cannot join
- Known bulky central nervous system disease.
- Inadequate hepatic function defined by aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 2.5 x upper limit of normal (ULN) and direct bilirubin > 4x ULN.
- Inadequate renal function defined by serum creatinine clearance/estimated clearance of <20 (ml/min).
- International ratio (INR) or partial thromboplastin time (PTT) > 2 x ULN, unless on a stable dose of anticoagulant for a thromboembolic event (provided this event is not an exclusion criteria).
- Inadequate bone marrow function defined by absolute neutrophil count (ANC) < 1000 cells/mm3, platelet count < 30,000 mm3, or hemoglobin < 8 g/dL.
- Echocardiogram with left ventricular ejection fraction < 40%.
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- Ongoing treatment with chronic immunosuppressant or systemic steroids (physiological replacement doses of steroids are allowed up to 12 mg/m2/d hydrocortisone or equivalent)
- Significant co-morbid condition or disease which in the judgment of the Investigator would place the subject at undue risk or interfere with the study; examples include, but are not limited to, cirrhotic liver disease, sepsis, recent significant traumatic injury, and other conditions.
- Known human immunodeficiency virus (HIV) positive status.
- Active Hepatitis B or Hepatitis C infections.
- Active CMV infection.
- Have suffered from a stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control and is not expected to resolve or stabilize within 3 months.
- Chronic atrial fibrillation with uncontrolled heart rate.
- Second primary malignancy that has required therapy in the last 2 years or is not in complete remission. This exclusion criterion does not exclude the following subjects: successfully treated non- metastatic basal cell or squamous cell skin carcinoma, or prostate cancer under control with hormonal therapy
- Subjects who have had a venous thromboembolic event (e.g., pulmonary embolism or deep vein thrombosis) requiring anticoagulation and who meet any of the following criteria:
- Have been on a stable dose of anticoagulation for < 1 month (except for acute line insertion induced thrombosis).
- Have had a Grade 2, 3, or 4 hemorrhage in the last 30 days
- Are experiencing continued symptoms from their venous thromboembolic event (e.g. continued dyspnea or oxygen requirement).
- Pregnant or lactating women.
- Contraindication to a study treatment/procedure or is anticipated to receive treatment/procedure that may preclude performance of study procedures.
- Subjects with Absolute Lymphocyte Count (ALC) ≤0.3 × 109/L or < 300 cells/mm3 (due to potential challenges with producing CART cells), per investigator judgement
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Israel1 site
Hadassah MO
Jerusalem, 9574869
Polina Stepensky, MD, 97226776679, Fainak@haddasah.org.il
About this study
Official title: A Phase 1a/b Open-Label Study to Evaluate Safety and Preliminary Efficacy of GPRC5D CART Therapy for the Treatment of Relapsed/Refractory Multiple Myeloma and Light-chain Amyloidosis.
A Phase 1a/b Open-Label Study to Evaluate Safety and Preliminary Efficacy of GPRC5D CART Therapy for the Treatment of Relapsed/Refractory Multiple Myeloma and Light-chain Amyloidosis.
- Being tested
- GPRC5D CART
- Keywords
- Multiple Myeloma, Amyloidosis
- Medical subject headings
- Multiple Myeloma, Immunoglobulin Light-chain Amyloidosis, Amyloidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GPRC5D CARTBiological
The GPRC5D CART is defines as autologous bone marrow derived T-cells transduced with anti-GPRC5D CAR lentiviral vector encoding the chimeric antigen receptor (CAR) targeted to human GPRC5D. The GPRC5D CART is provided cryopreserved.
| Study group | Role | What they receive |
|---|---|---|
| GPRC5D CART | Experimental | In the Phase 1a dose-escalation phase, eligible participants for Cohorts 1, 2, 3 and 4 will receive a single dose of either 50× 10˄6, 150 × 10˄6, 300 × 10˄6 or 450 × 10˄6 GPRC5D CART cells, respectively. The Phase 1b expansion part will enroll additional participants at the maximum tolerated dose, as determined during dose escalation. Receives: Biological: GPRC5D CART |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Related Serious Adverse Events and Adverse Events of Special Interest following GPRC5D CART Therapy
Incidence of Treatment-Related Serious Adverse Events and Adverse Events of Special Interest will be assessed
Measured: 24 months following infusion
Maximum tolerated dose (MTD) of GPRC5D CART cells in Phase 1a.
The maximum tolerated single dose (MTD) of GPRC5D CART cells will be determined during Phase 1a dose-escalation stage.
Measured: 21 days following infusion
Secondary outcomes (5)
Overall response rate
Overall Response Rate is defined by proportion of subjects with Partial Response or better per IMWG Criteria for MM, and Partial Response or better per Hematologic Response Criteria for AL
Measured: 24 months following infusion
Complete response rate
Complete Response Rate is defined by proportion of subjects with Complete Response per IMWG Criteria for MM or per Hematologic Response Criteria for AL
Measured: 24 months following infusion
Progression-Free Survival
Progression-Free Survival is defined as the time from the date of the initial infusion the date of first documented disease progression, or death due to any cause, whichever occurs first
Measured: 24 months following infusion
Overall Survival
Overall Survival is defined by the date of the initial infusion to the date of the patient's death due to any cause
Measured: 24 months following infusion
MRD negativity rate
MRD Negativity Rate is defined by proportion of subjects with MRD, defined as the absence of clonal plasma cells on bone marrow aspirate (minimum test sensitivity to detect 1 in 10x5 nucleated cells (10-5 threshold))
Measured: At 1, 6, 12, 18, and 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2026
- Study start1 Nov 2026 (estimated)
- Primary completion31 Dec 2032 (estimated)
- Study completion31 Dec 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed/Refractory Multiple Myeloma (RRMM)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- The phase 1a dose-escalation part will follow a 3+3 design and include up to 4 dose level cohorts. This will be followed by a phase 1b expansion part, in which participants will be enrolled to receive treatment at the maximum tolerated dose (MTD).
- Masking
- None (open label)
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hadassah Medical Organization
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Polina Stepensky, Hadassah Medical Organization
- Investigators
- Polina Stepensky, MD, Principal investigator, Hadassah Medical Organization
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07874334
- Sponsor's protocol ID
- GPRC5D CART-01
- Status last verified
- Oct 2026
- First submitted
- 8 Oct 2026
- Last updated
- 20 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided