Clinical trial NCT01842308: Carfilzomib and Melphalan Before Stem Cell Transplant in Treating Patients With Multiple Myeloma
Official title: A Phase 1/2 Trial of Carfilzomib and Melphalan and Conditioning for Autologous Stem Cell Transplantation for Multiple Myeloma (CARAMEL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: DS Stage I Plasma Cell Myeloma
DS Stage II Plasma Cell Myeloma
DS Stage III Plasma Cell Myeloma
Refractory Plasma Cell Myeloma
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2013-04-29
Enrollment: 50
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 I/II trial studies the side effects and best dose of carfilzomib when given together with melphalan and to see how well they work in treating patients with multiple myeloma before stem cell transplant. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving carfilzomib together with melphalan may kill more cancer cells.

Detailed description: PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of carfilzomib that can be added to high dose melphalan as part of conditioning chemotherapy for myeloma. (Phase I) II. To determine the efficacy of the combination in patients with myeloma undergoing stem cell transplantation, as defined by achievement of complete response (CR). (Phase II)

SECONDARY OBJECTIVES:

I. To examine the toxicities associated with addition of carfilzomib to high dose melphalan in patients with multiple myeloma (MM).

II. To determine the progression free rate at 1 and 2 years post registration.

TERTIARY OBJECTIVES:

I. To determine the proportion of patients achieving a minimal residual disease (MRD) negative status.

II. To assess the HevyLite assay prior to and during treatment.

OUTLINE: This is a phase I, dose-escalation study of carfilzomib followed by a phase II study.

CONDITIONING: Patients receive carfilzomib intravenously (IV) over 30 minutes on days -6, -5, -2, and -1. Patients also receive melphalan IV over 1 hour on days -4 and -3.

TRANSPLANT: Patients undergo autologous stem cell transplant on day 0.

After completion of study treatment, patients are followed up at day 30, day 100, and then every 90 days for up to 5 years.

Eligibility criteria: Inclusion Criteria:

* Serum creatinine =\< 2 mg/dL
* Absolute neutrophil count \>= 1000/uL
* Platelet count \>= 50,000/uL
* Hemoglobin \>= 8.0 g/dL
* Diagnosis of symptomatic MM
* Measurable disease of multiple myeloma at the time of baseline values for disease assessment as defined by at least one of the following:

  * Serum monoclonal protein \>= 1.0 g/dL
  * \>= 200 mg of monoclonal protein in the urine on 24 hour electrophoresis
  * Serum immunoglobulin free light chain \>=10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
  * Bone marrow plasma cells \>= 30%
  * NOTE: For patients with no relapse prior to transplant, measurable disease at the time of diagnosis
  * NOTE: For patients who have had a disease relapse prior to transplant, measurable disease at the time of the most recent relapse immediately prior to transplant; NOTE: If the patient had treatment for the relapsed disease prior to transplant, the patient must have measurable disease at the time of relapse prior to this therapy
* Patient is considered for autologous stem cell transplantation with full dose melphalan (200 mg/m\^2)
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
* Recovered from toxicity of previous chemotherapy (excludes grade 1 neurotoxicity and hematological toxicity)
* Provide informed written consent
* Ejection fraction \>= 45%
* Corrected pulmonary diffusion capacity of greater than or equal to 50%
* Forced expiratory volume in 1 second (FEV1) \>= 50%
* Forced vital capacity (FVC) \>= 50%
* Negative pregnancy test performed =\< 7 days prior to registration, for women of childbearing potential only
* Willing to return to Mayo Clinic Rochester, Mayo Clinic Arizona, Mayo Clinic Florida for treatment

  * Note: During the active monitoring phase of a study (i.e., active treatment and observation), participants must be willing to return to the consenting institution for follow-up
* Willing to provide blood and bone marrow samples for correlative research purposes

Exclusion Criteria:

* Prior autologous or allogeneic bone marrow/peripheral blood stem cell transplant
* More than two prior regimens for therapy of MM
* Myocardial infarction within 6 months prior to enrollment, or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; NOTE: Prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
* Seroreactivity for human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV) I or II, hepatitis B virus (HBV), hepatitis C virus (HCV)
* Other active malignancy \< 2 years prior to registration; EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: If there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer
* Any of the following:

  * Pregnant women or women of reproductive capability who are unwilling to use effective contraception
  * Nursing women
  * Men who are unwilling to use a condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking the drug and for 28 days after stopping treatment
* Other co-morbidity, which would interfere with patient's ability to participate in the trial, e.g. uncontrolled infection, uncompensated lung disease
* Concurrent chemotherapy, radiotherapy, or any ancillary therapy considered investigational; NOTE: Bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment
* Known allergies to any of the components of the investigational treatment regimen or required ancillary treatments

Primary outcomes:
measure: Determine Maximum Tolerated Dose by the Number of Patients With a DLT Per Dose Level
timeFrame: Up to day 30
measure: Percentage of Patients With Complete Responses, Defined as a Complete Response Noted as the Objective Status on Two Consecutive Evaluations (Phase II)
timeFrame: Up to 5 years
Secondary outcomes:
measure: Adverse Event Rate, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
timeFrame: Up to 5 years
measure: Complete Response Rate at Day 100
timeFrame: At day 100
measure: Progression Free Percentage at 1 and 2 Years Post Registration
timeFrame: At 1 year and 2 years
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida
state: Florida
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Suzanne Hayman
role: PRINCIPAL_INVESTIGATOR
References: