Overview

High-Dose Weekly Carfilzomib Plus Cyclophosphamide and Dexamethasone in the Treatment of Relapsed Multiple Myeloma

Status:
Active, not recruiting
Trial end date:
2022-12-31
Target enrollment:
0
Participant gender:
All
Summary
The purpose of this study is to find out what effects carfilzomib has on relapsed multiple myeloma when administered in combination with cyclophosphamide and dexamethasone.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Canadian Cancer Trials Group
Collaborators:
Amgen
Canadian Myeloma Research Group
Myeloma Canada Research Network
Treatments:
BB 1101
Cyclophosphamide
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Criteria
Inclusion Criteria:

- Relapsed symptomatic multiple myeloma as per the International Myeloma Working group
criteria [Palumbo 2009].

- Measurable disease, as defined by one or more of the following (assessed within 21
days prior to registration):

- Serum M-protein ≥ 5 g/L (0.5g/dL)

- Urine Bence-Jones protein ≥ 200 mg/24 hours

- Involved serum free light chain (FLC) measurement ≥ 100 mg/L (10 mg/dL), provided
serum FLC ratio is abnormal (abnormal if FLC ratio is <0.26 or >1.65)

- Biopsy proven plasmacytoma

- For IgA patients whose disease can only be reliably measured by serum
quantitative immunoglobulin (qIgA) ≥ 750 mg/dL (0.75 g/dL)

- Prior treatment with at least one, but no more than three, regimens for multiple
myeloma

- Documented relapse or progressive disease on or after any regimen (subjects refractory
to the most recent line of therapy are eligible except those who are refractory to
bortezomib and cyclophosphamide as described in exclusion criteria 1.

- Achieved a response to at least one prior regimen (defined as ≥ 25% decrease in
M-protein)

- Age ≥ 18 years.

- Life expectancy ≥ 3 months.

- ECOG performance status 0-2.

- Laboratory Requirements (must be done within 21 days of registration):

- Hematology:

- Absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L

- Hemoglobin ≥ 8 g/dL (80 g/L) (subjects may be receiving red blood cell (RBC)
transfusions in accordance with institutional guidelines)

- Platelet count ≥ 50 × 10^9/L, independent of platelet transfusions for 7 days. (≥
30 × 10^9/L if myeloma involvement in the bone marrow is ≥ 50%)

- Biochemistry:

- ALT ≤ 3.5 x UNL

- Serum direct bilirubin ≤ 2 mg/dL (34 μmol/L) (only required if total bilirubin ≥
2mg/dL (34μmol/L)

- Creatinine clearance (CrCl) ≥ 30 mL/minute (Crockcroft and Gault formula) and not
on dialysis.

- Patient consent must be appropriately obtained in accordance with applicable local and
regulatory requirements. Each patient must sign a consent form prior to enrollment in
the trial to document their willingness to participate.

- Patients must be accessible for treatment and follow up. Patients registered on this
trial must be treated and followed at the participating centre.

- In accordance with CRO policy, protocol treatment is to begin within 2 working days of
patient registration.

- Women/men of childbearing potential must have agreed to use a highly effective
contraceptive method.

Exclusion Criteria:

- Refractory to any proteasome inhibitor therapy (bortezomib, ixazomib, etc.) Refractory
disease is defined as failure to respond to the proteasome inhibitor, initial response
followed by progression while on a proteasome inhibitor, or relapse within 60 days of
stopping proteasome inhibitor therapy.

- Prior carfilzomib treatment.

- POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and
skin changes)

- Waldenström's macroglobulinemia or IgM myeloma

- Current or previous Plasma cell leukemia defined as (> 2.0 × 10^9/L circulating plasma
cells by standard differential)

- Chemotherapy or investigational agent within 3 weeks prior to registration or antibody
therapy within 6 weeks prior to registration

- Radiotherapy to multiple sites within 28 days prior to registration; localized
radiotherapy to a single site within 7 days prior to registration

- Plasmapheresisis within 14 days of registration.

- Pregnant or lactating females.

- Major surgery within 21 days prior to registration.

- Active, uncontrolled bacterial, fungal, or viral infection.

- Concurrent amyloidosis

- Known human immunodeficiency virus infection.

- Active hepatitis B or C infection.

- Myocardial infarction within 4 months prior to registration, NYHA Class III or IV
heart failure, uncontrolled angina, history of severe coronary artery disease, severe
uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic
evidence of acute ischemia or grade 3 conduction system abnormalities unless subject
has a pacemaker.

- Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to
registration.

- Other malignancy, including MDS, within the past 3 years with the exception of
adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer;
carcinoma in situ of the cervix or breast; prostate cancer of Gleason Score 6 or less
with stable prostate-specific antigen levels; or cancer considered cured by surgical
resection or unlikely to impact survival during the duration of the study, such as
localized transitional cell carcinoma of the bladder or benign tumours of the adrenal
or pancreas.

- Significant neuropathy (≥ grade 3, or grade 2 with pain) within 14 days prior to
registration.

- Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize
carfilzomib).

- Contraindication to any of the required concomitant drugs or supportive treatments,
including hypersensitivity antiviral drugs, or intolerance to hydration due to
preexisting pulmonary or cardiac impairment.

- Ongoing graft-versus-host disease.

- Subjects with pleural effusions requiring thoracentesis or ascites requiring
paracentesis within 14 days prior to registration.

- Any other clinically significant medical disease or condition that, in the
Investigator's opinion, may interfere with protocol adherence or a subject's ability
to give informed consent.