Relapsed/Refractory Multiple Myeloma (MM)
Conditions
Keywords
Multiple Myeloma (MM)
Brief summary
A Phase 1a/1b Open-Label Study with Dose Escalation and Expansion Phases to Evaluate Safety and Preliminary Efficacy of Naïve HBI0101 CART Therapy for the Treatment of Relapsed/Refractory Multiple Myeloma.
Interventions
BIOLOGICALNaive HBI0101 CAR-T
Naïve HBI0101 CART is defined as autologous T cells transduced ex-vivo with anti-BCMA CAR retroviral vector encoding the chimeric antigen receptor (CAR) targeted to human BCMA. The Naïve HBI0101 CART is provided cryopreserved.
Sponsors
Hadassah Medical Organization
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. ≥18 years of age at the time of signing informed consent. 2. Voluntarily signed informed consent form. 3. Diagnosis of relapsed/refractory multiple myeloma (Parts 1a and 1b), with measurable disease at screening visit as follows: Multiple Myeloma (at least one of the criteria below): 1. Serum M-protein greater or equal to 0.5 g/dL. 2. Urine M-protein greater or equal to 200 mg/24 h. 3. 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. 4. A biopsy-proven evaluable plasmacytoma\*. 5. Bone marrow plasma cells \> 10% of total bone marrow cells\*. 6. Non secretory patient will be allowed provided they have measurable disease by PET-CT or bone marrow aspiration, as designated\*. * Results pre-dating the Screening visit by up to 28 days may be used to establish eligibility. 4. R/R MM subjects must have been exposed to at least three prior lines of therapy including the following agents: 1. proteasome inhibitor 2. immunomodulatory (IMiDs) agent 3. anti-CD38 antibody 5. For part 1a: At least one of the following risk factors: a. Extra-medullary disease (EMD) - defined as a MM lesion that is not connected to a bone. b. previous exposure to an anti-BCMA therapy. 6. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2. 7. 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. 8. Recovery to ≤ Grade 2 or baseline of any non-hematologic toxicities due to prior treatments, excluding alopecia and Grade 3 neuropathy, and toxicities that are irreversible and not expected to interfere with study treatment or pose safety concerns, per investigator judgement. 9. Ability and willingness to adhere to the study visit schedule and all protocol requirements. 10. For subjects with relapsed multiple myeloma who have previously undergone allogenic stem cell transplantation: no evidence of graft versus host disease after cessation of any immunosuppressive therapy for at least one month before recruitment to the study.
Exclusion criteria
1. Contraindication to a study treatment/procedure or is anticipated to receive treatment/procedure that may preclude performance of study procedures. 2. Known bulky central nervous system disease. 3. Inadequate hepatic function defined by aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \> 2.5 x upper limit of normal (ULN) and/or direct bilirubin \> 4x ULN. 4. Inadequate renal function defined by estimated clearance of \<20(ml/min). 5. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine the Maximum Tolerated Dose (MTD) | 21 days after infusion | MTD will be determined by dose limiting toxicities |
| Evaluate safety of Naïve HBI0101 CART in Parts 1a and 1b | 24 Months after infusion | Incidence of Serious Adverse Events and Adverse Events of Special Interest related to study treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate Progression-Free Survival in participants treated with Naïve HBI0101 CART | 24 Months after infusion | — |
| Evaluate Duration of Response in participants treated with Naïve HBI0101 CART | 24 Months after infusion | — |
| Evaluate clinical response to Naïve HBI0101 CART | 24 Months after infusion | Overall response rate- Percentage of participants who achieved at least partial response |
| Evaluate persistence of Naïve HBI0101 CART in treated participants | 24 Months after infusion | Quantification of Naïve HBI0101 CART in the blood |
| Evaluate proportion of MRD negative subjects in participants treated with Naïve HBI0101 CART. | 24 Months after infusion | — |
| Evaluate Overall Survival in participants treated with Naïve HBI0101 CART | 24 Months after infusion | — |
Countries
Israel
Contacts
Primary ContactPolina Stepensky, MD
Outcome results
None listed