This is an open-label, single-arm, non-randomized multicenter Phase 2 study evaluating
RAPA-201 cells in subjects with relapsed, refractory multiple myeloma.
After a subject consents to the study, an apheresis procedure will be performed to collect
cells to manufacture the investigational product, RAPA-201 cells. During Cycle 1, subjects
will receive pentostatin and low-dose, dose-adjusted Cyclophosphamide (PC regimen), but will
not receive RAPA-201 cells. During Cycles 2 and beyond, Subjects will receive a conditioning
regimen consisting of the PC regimen followed by the RAPA-201 cell infusions.
Subjects will receive up to five cycles of treatment. If a subject has stable disease at the
end of cycle 4, they will receive an additional four cycles of PC regimen+RAPA-201 cells.
All subjects who complete the active treatment portion of the study, prematurely terminate
the study, or subjects who discontinue active treatment due to a toxicity attributable or
related to the study drug will complete the follow-up portion of the study (approximately one
year).
Patients who experience progressive disease will be taken off study.
Inclusion Criteria:
- Male or female patients ≥ 18 years of age.
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
- Diagnosis of relapsed, refractory multiple myeloma.
- Exposure to at least three different prior lines of therapy including exposure to at
least two proteosome inhibitors (e.g. bortezomib), and at least two immunomodulatory
drugs (e.g. lenalidomide) and at least one anti-CD38 monoclonal antibody agent (e.g.
daratumumab). To qualify as a prior line of therapy, ≥ 2 cycles of therapy must be
administered unless the disease is refractory, or the regimen is not tolerated.
Documentation of a prior line of therapy must include at least one of the following
three items: [1] medical records detailing prior treatment, best response to
treatment, and date of progression; [2] myeloma markers (SPEP, UPEP, Immunoglobulin,
FLC) at time of treatment and progression; or, [3] documentation by
investigator/treating physician to be included in patient's medical and research
record (for example, note in electronic medical record), indicating prior treatment,
best response to treatment, and data of progression.
- Refractory status to ≥ one proteasome inhibitor AND ≥ one immunomodulatory drug.
Refractory disease is defined as <25% reduction in M-protein/free light chain
difference (involved vs. uninvolved) or disease progression during treatment or ≤ 60
days after treatment cessation. Patient may or may not be refractory to anti-CD38
therapy.
- Presence of secretory myeloma/measurable disease, as defined by ONE of the following:
1. Serum M-protein (SPEP) ≥ 0.5 mg/dL or
2. Urine M-protein (UPEP) ≥ 200 mg/24 hours; or
3. Light chain MM: Serum free light chain (FLC) assay ≥ 10 mg/dL (100 mg/L) and
abnormal serum immunoglobulin kappa/lambda FLC ratio.
- Must have a potential source of autologous T cells potentially sufficient to
manufacture RAPA-201 cells, as defined by a circulating CD3+ T cell count ≥ 300
cells/µL.
- Prior to apheresis, patients must be ≥ 14 calendar days from last myeloma therapy,
major surgery, radiation therapy and participation in investigational trials.
- Patients must have recovered from clinical toxicities (resolution of CTCAE toxicity to
a value of ≤ 2).
- Left ventricular ejection fraction (LVEF) by MUGA or 2-D echocardiogram within
institution normal limits, with an LVEF level of ≥ 40%.
- Serum creatinine ≤ to 2.5 mg/dL.
- Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ to 3 x upper
limit of normal (ULN).
- Absolute neutrophil count (ANC) of ≥ 1000 cells/µL (independent of growth factor
support for at least 7 days prior to screening).
- Platelet count of ≥ 50,000 cells/µL, with value obtained (independent of growth factor
support or transfusion support for at least 7 days prior to screening).
- Hemoglobin count ≥ 8 grams/µL (independent of growth factor support or transfusion
support for at least 7 days prior to screening).
- Bilirubin ≤ 1.5 (except if due to Gilbert's disease).
- Corrected DLCO ≥ 50% (Pulmonary Function Test).
- No history of abnormal bleeding tendency, as defined by any inherited coagulation
defect or history of internal bleeding.
- Voluntary written consent must be given before performance of any study related
procedure not part of standard medical care, with the understanding that consent may
be withdrawn by the patient at any time without prejudice to future medical care.
Exclusion Criteria:
- Prior allogeneic stem cell transplantation.
- Current plasma cell leukemia (circulating myeloma > 20% of leukocytes).
- Other active malignancy (except for non-melanoma skin cancer).
- Non-secretory multiple myeloma (difficult to assess by IMWG criteria).
- Evidence of systemic AL Amyloidosis involving any vital organ. Incidental histologic
demonstration of amyloid deposition in marrow/within plasmacytoma is not considered
organ involvement.
- Life expectancy <4 months.
- Patients seropositive for HIV, hepatitis B, or hepatitis C.
- Uncontrolled hypertension.
- History of cerebrovascular accident within 6 months prior to enrollment.
- Myocardial infarction within 6 months prior to enrollment.
- NYHA class III/IV congestive heart failure.
- Uncontrolled angina/ischemic heart disease.
- Subjects with known central nervous system disease.
- Pregnant or breastfeeding patients.
- Patients of childbearing age, or males who have a partner of childbearing potential,
who are unwilling to practice contraception.
- Patients may be excluded at PI discretion or if it is deemed that allowing
participation would represent an unacceptable medical or psychiatric risk.
