Overview

Phase Ib Study of SAR650984 in Combination With Carfilzomib for Treatment of Relapsed or Refractory Multiple Myeloma

Status:
Recruiting
Trial end date:
2024-12-31
Target enrollment:
0
Participant gender:
All
Summary
This phase Ib trial studies the side effects and best dose of isatuximab when given together with carfilzomib with or without dexamethasone and lenalidomide in treating patients with multiple myeloma that has returned after a period of improvement (relapsed) or has not respond to previous treatment (refractory). Immunotherapy with monoclonal antibodies, such as isatuximab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as dexamethasone and lenalidomide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving isatuximab and carfilzomib with or without dexamethasone and lenalidomide may be a better treatment for patients with multiple myeloma.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Thomas Martin, MD
University of California, San Francisco
Collaborators:
Amgen
Sanofi
Treatments:
Dexamethasone
Criteria
Inclusion Criteria:

1. Males or females, age 18 years or older

2. Diagnosis of multiple myeloma (MM) and documentation of treatment

- ARM 1: Must have prior exposure to an immunomodulatory drug (IMiD) and proteasome
inhibitor (PI) and have had 2 prior regimens/lines of therapy; but there is no
maximum number of prior regimens, and prior autologous bone marrow transplant is
acceptable if > 12 weeks from transplantation; patients may have received prior
carfilzomib (sensitive, relapsed and refractory [having progressed while
receiving carfilzomib or within 60 days of stopping carfilzomib] are all
eligible), but must be > 4 weeks from last dosing of carfilzomib

- ARM 2: Must have had at least 1 but no more than 3 prior lines of anti-myeloma
therapy; may be refractory to lenalidomide but sensitive to carfilzomib; prior
exposure to carfilzomib is allowed but may not be refractory to carfilzomib;
subjects must be >= 8 weeks from last carfilzomib therapy

- A line of therapy is defined as a course of therapy that is not interrupted by
progressive disease; for example, induction therapy, autologous stem cell
transplantation, and maintenance therapy without intervening progressive disease
is one line of therapy

3. Confirmed evidence of relapse/disease progression from immediately prior MM therapy or
relapsed and refractory to the immediately prior treatment; relapsed and refractory
disease is defined as those who are non-responsive (< minimal response) on salvage
therapy or experience disease progression within 60 days of last therapy in patients
who have achieved an MR or better to previous therapy; relapsed disease is defined as
previously treated myeloma that progresses and requires the initiation of salvage
therapy but does not meet IMWG criteria for relapsed and refractory

4. Patients may have received prior carfilzomib (sensitive, relapsed and refractory all
eligible); response and duration of prior carfilzomib therapy must be known

5. Patients must have measurable disease defined as at least one of the following:

- Serum M-protein >= 0.5 g/dl (>= 5 g/l)

- Urine M-protein >= 200 mg/24 hours (h)

- Serum free light chain (FLC) assay: involved FLC level >= 10 mg/dl (>= 100 mg/l)
and an abnormal serum free light chain ratio (< 0.26 or > 1.65)

- Quantitative immunoglobulin > 500 mg/dL, only for immunoglobulin (Ig)A and (Ig)D
myeloma when the protein electrophoresis under-represents disease burden

- Biopsy proven plasmacytoma > 1x1 cm (should be measured within 28 days prior to
initial investigational agent dosing)

6. Subject has an Eastern Cooperative Oncology Group (ECOG) =< 2 performance status OR
Karnofsky >= 60% performance status

7. Females of childbearing potential (FCBP)

- A female of childbearing potential is a sexually mature woman who: 1) has not
undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally
postmenopausal for at least 24 consecutive months

- Females of childbearing potential must have a negative serum beta-human chorionic
gonadotropin (beta-hCG) pregnancy test with a sensitivity of at least 50
milli-international units per milliliter(mIU/mL), within 10-14 days of study
start (during screening)

- FCBP must also agree to ongoing pregnancy testing. Pregnancy testing is not
required for post-menopausal or surgically sterilized women

- Females must agree to avoid pregnancy during the study and must agree to use a
medically acceptable method of birth control as determined by the study doctor
while participating in the study and for at least 5 months after the last dose of
study medication

8. Men must agree to use contraception (i.e. a latex condom) during sexual contact with a
FCBP even if they have had a successful vasectomy and agree to not donate sperm for 5
months after last study therapy (SAR650984, lenalidomide and carfilzomib).

9. Voluntary written informed consent before performance of any study-related procedure
not part of routine medical care with the understanding that consent may be withdrawn
by the subject at any time without prejudice to future medical care

10. Ability to understand the purpose and risks of the study and provide signed and dated
informed consent and authorization to use protected health information (in accordance
with national and local subject privacy regulations)

11. For patients with platelets > 100,000 cells/ul (100x10^9/L) able to take aspirin daily
as prophylactic anticoagulation therapy for ARM 2 (patients intolerant to aspirin may
use warfarin, low-molecular-weight heparin or equivalent anti-platelet therapy)

12. Inclusion Clinical Laboratories Criteria. The following laboratory results must be
met:

- Absolute neutrophil count (ANC) > 1,000 cells/dL (1.0 x 10e9/L) (growth factor
cannot be used within the previous 7 days)

- Hemoglobin >= 8.0 g/dl (without transfusion within the previous 7 days)

- Platelet count > 75,000 cells/dL (75 x 10e9/L)

- Creatinine clearance >= 30 mL/min (Cockcroft-Gault equation)

- Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST)
or serum glutamate pyruvate transaminase (SGPT)/alanine aminotransferase (ALT) <
2.5 x upper limit of normal (ULN)

- Total bilirubin =< 1.5 x ULN

- Serum calcium (corrected for albumin) level at or below the ULN range (treatment
of hypercalcemia is allowed and subject may enroll if hypercalcemia returns to
normal with standard treatment) prior to study therapy initiation

- Left ventricular ejection fraction (LVEF) >= 40% (by echocardiogram or multigated
acquisition scan (MUGA) testing)

- Fasting glucose under control (< 150 mg/dL [8.3 mmol/L])

Exclusion Criteria:

Patients who have met all the inclusion criteria listed above will be screened for the
following exclusion criteria:

1. Diagnosed or treated for another malignancy within 3 years of enrollment, with the
exception of complete resection of basal cell carcinoma or squamous cell carcinoma of
the skin, an in situ malignancy, low-risk prostate cancer after curative therapy or
complete resection of other advanced malignancy with the expectation that the patient
has received curative therapy

2. Patient has received other investigational drugs with 21 days before enrollment (or
must be > than four half-lives of the experimental agent); no prior SAR650984
anti-CD38 antibody therapy allowed

3. History of significant cardiovascular disease unless the disease is well-controlled or
history of myocardial infarction in the past 6 months; significant cardiac diseases
includes second/third degree heart block; significant conduction abnormalities,
significant ischemic heart disease; poorly controlled hypertension; congestive heart
failure of New York Heart Association (NYHA) class II or worse (slight limitation of
physical activity; comfortable at rest, but ordinary physical activity results in
fatigue, palpitation, or dyspnea) and inability to tolerate intravenous hydration
necessary for study therapy administration

4. Prior autologous or allogeneic peripheral stem cell transplant within 12 weeks of the
first dose of study treatment

5. Daily requirement for corticosteroids (> 10 mg prednisone once daily (QD) or
equivalent)

6. Patients with evidence of significant mucosal or internal bleeding

7. Prior radiation therapy or chemotherapy within 2 weeks or major surgical procedure
within 4 weeks of the first dose of study treatment

8. Known active infection requiring parenteral or oral anti-infective treatment, once a
patient has completed antibiotics and symptoms of infection have resolved to < grade
2, they are then considered eligible from an infection standpoint

9. Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or
confuse follow-up evaluation

10. Any medical conditions that, in the Investigator's opinion, would impose excessive
risk to the patient; examples of such conditions include any pre-existing kidney
disease (acute or chronic, unless renal insufficiency is felt to be secondary to MM),
hypertension, active seizure disorder or pulmonary diseases that would impose
excessive risk to the patient

11. Patient has hypersensitivity to boron, mannitol sucrose, histidine (as base and
hydrochloride salt) and polysorbate 80 or any of the components of study therapy
including required prophylactic medications

12. Known human immunodeficiency virus (HIV) seropositivity or active hepatitis B or C
viral infection

13. Neuropathy >= grade 3 or painful neuropathy >= grade 2 (National Cancer Institute
Common Terminology Criteria for Adverse Events [NCI CTCAE] version [v]4.03)

14. Gastro-intestinal abnormalities, including bowel obstruction, inability to take oral
medication, requirement for intravenous (IV) alimentation, active peptic ulcer or
prior surgical procedures or bowel resection affecting absorption