Clinical trial NCT03756896: Carfilzomib, Pomalidomide, and Dexamethasone in Treating Patients With High-Risk Multiple Myeloma
Official title: Maintenance Therapy With Carfilzomib, Pomalidomide and Dexamethasone (CPd) in High-Risk Myeloma Patients: A Phase 2 Study With a Safety Run-In
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Plasma Cell Myeloma
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: Amgen
name: National Cancer Institute (NCI)
name: National Institutes of Health (NIH)
First posted: 2018-11-28
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase II trial studies how well carfilzomib, pomalidomide, and dexamethasone work in treating patients with high-risk multiple myeloma. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as pomalidomide and dexamethasone, 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 carfilzomib, pomalidomide, and dexamethasone may work better in treating patients with multiple myeloma.

Detailed description: PRIMARY OBJECTIVE:

I. To determine the ≥ complete response (CR) rates with carfilzomib, pomalidomide and dexamethasone (CPd) maintenance.

SECONDARY OBJECTIVES:

I. To determine the improved progression free survival (PFS) with CPd maintenance among high-risk patients.

II. To determine the best response rates (very good partial response rate \[VGPR\], stringent complete response \[sCR\] rate) with CPd maintenance.

II. To evaluate the safety of the CPd combination as maintenance regimen.

III. To characterize safety in subjects who receive CPd maintenance.

IV. To evaluate the duration of response (DOR).

V. To evaluate the overall survival (OS) in high-risk patients.

VI. To evaluate the minimal residual disease (MRD) detection with CPd maintenance.

OUTLINE:

Patients receive carfilzomib intravenously (IV) over 30 minutes on days 1, 8, and 15, pomalidomide orally (PO) daily on days 1-21, and dexamethasone PO daily on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months.

Eligibility criteria: Inclusion Criteria:

* Patients must meet the following criteria on screening examination to be eligible to participate in the study; all laboratory assessments should be performed within 28 days of initiation of protocol therapy unless otherwise specified; subject is, in the investigator's opinion, willing and able to comply with the protocol requirements
* Subject has given voluntary signed written informed consent before performance of any study-related procedure that is not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to their future medical care
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1
* Subject is a transplant-eligible patient that have undergone autologous stem cell transplant (ASCT) within one year of their diagnosis and have achieved ≥ partial response (PR) based on International Myeloma Working Group (IMWG) standard criteria
* Patients with high risk disease defined as

  * Presence of del(17p); t(4;14); t(14;16); t(14;20) by fluorescence in situ hybridization (FISH) or by cytogenetics (CTG)
  * Plasma cell leukemia at diagnosis with ≥ 20% circulating plasma cells on peripheral blood
* Subject agrees to refrain from blood donations during therapy on study and for 90 days after therapy is completed
* Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 milli-International units (mIU)/mL within 10-14 days prior to and again within 24 hours of starting pomalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking pomalidomide through 90 days after the last dose of study drug; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy from the time of signing the informed consent form through 90 days after the last dose of study drug; all patients must be registered in and must comply with all requirements of the pomalidomide Risk Evaluation and Mitigation Strategies (REMS) program; male subjects should refrain from sperm donation for at least 90 days after the last dose of carfilzomib or pomalidomide

  * FCBP refers to sexually mature female, regardless of sexual orientation or whether they have undergone tubal ligation, who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally menopausal for at least 24 consecutive months

Exclusion Criteria:

* Diagnosed with smoldering multiple myeloma (MM), monoclonal gammopathy of undetermined significance, Waldenstrom's macroglobulinemia, polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, amyloidosis or standard risk myeloma or secondary plasma cell leukemia
* High risk patients that did not achieve ≥ PR after stem cell transplant
* Participant has ≥ grade 2 peripheral neuropathy on clinical examination within 21 days before initiation of protocol therapy
* Creatinine clearance \< 30 mL/min (either actual or calculated value), within 21 days of initiation of protocol therapy; the Cockcroft-Gault formula should be used for calculating creatinine clearance values
* Platelet count \< 75,000 cells/mm³ at time of screening evaluation; transfusion may not be used to meet platelet eligibility criteria within 7 days of obtaining screening evaluation
* Participants with an absolute neutrophil count (ANC) \< 1000 cells/mm³ at time of screening evaluation; growth factors may not be used to meet ANC eligibility criteria within 14 days of obtaining screening evaluation
* Participants with hemoglobin level \< 8.0 g/dL, at time of screening; transfusion may not be used to meet eligibility criteria within 7 days of obtaining screening evaluation
* Bilirubin \> 1.5 x institutional upper limit of normal (ULN), within 21 days of initiation of protocol therapy
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]), alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]), or alkaline phosphatase \> 3 x institutional ULN, within 21 days of initiation of protocol therapy
* Other ongoing or prior anti-myeloma therapy; patients may be receiving concomitant therapy with bisphosphonates and low dose corticosteroids (e.g., prednisone up to but no more than 10 mg p.o. once daily \[q.d.\] or its equivalent) for symptom management and comorbid conditions; doses of corticosteroid should be stable for at least 7 days prior to study treatment)
* Known significant cardiac abnormalities including:

  * Congestive heart failure, New York Heart Association (NYHA) class III or IV
  * Uncontrolled angina, arrhythmia or hypertension
  * Myocardial infarction within the past six months
  * Any other uncontrolled or severe cardiovascular condition
  * Prior cerebrovascular event with residual neurologic deficit
* Serious, intercurrent illness including, but not limited to, clinically relevant active infection, known active hepatitis B or C viral infection, known human immunodeficiency virus (HIV) infection, uncontrolled diabetes mellitus, or serious co-morbid medical conditions such as chronic restrictive pulmonary disease, and cirrhosis
* Any condition, including laboratory abnormalities, that in the opinion of the investigator places the subject at unacceptable risk if he/she were to participate in the study
* Prior malignancy (within the last 5 years) except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer
* Known hypersensitivity to acyclovir or similar anti-viral drug
* Known intolerance to steroid therapy
* Contraindication or prior intolerance to thromboembolic prophylaxis with aspirin, warfarin or low-molecular weight heparin
* Participants with known central nervous system (CNS) disease
* Poor tolerability or known allergy to any of the study drugs or compounds of similar chemical or biologic composition to dexamethasone, boron or mannitol
* Female participants pregnant or breast-feeding
* Participants who have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from side effects of the surgery
* Participants with any significant history of non-compliance to medical regimens or unwilling or unable to comply with the instructions given to him/her by the study staff

Primary outcomes:
measure: ≥ Complete response (CR) rates
timeFrame: Up to 2 years after study start
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: From first dose until documented progression or death, assessed at 18 months
measure: Best response on-study
timeFrame: Up to 2 years after study start
measure: Objective response rate (ORR) defined as the proportion of treated subjects who achieve a best response of CR, stringent complete response (sCR), very good partial response (VGPR), or partial response (PR)
timeFrame: Up to 2 years after study start
measure: Duration of response (DOR)
timeFrame: From first response (PR or better) until a progression event (documented progression or death), assessed up to 2 years
measure: Overall survival (OS)
timeFrame: Up to 2 years after study start
measure: Minimal residual disease (MRD) detection
timeFrame: Up to 2 years after study start
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University Hospital/Winship Cancer Institute
state: Georgia
Study officials:
affiliation: Emory University
name: Ajay Nooka, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: