Carfilzomib and Dexamethasone in Treating Patients With Multiple Myeloma Who Previously Underwent a Stem Cell Transplant (CARAMEL 2)

A Phase 2 Trial of Carfilzomib Consolidation After Autologous Stem Cell Transplantation for Multiple Myeloma(CARAMEL 2)

This phase II trial studies how well carfilzomib and dexamethasone work in treating patients with multiple myeloma who previously underwent a stem cell transplant. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunosuppressive therapy, such as dexamethasone, may improve bone marrow function and increase blood cell counts. Giving carfilzomib together with dexamethasone may be an effective treatment for multiple myeloma.

Study Overview

• Status: Withdrawn
• Conditions: Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage III Multiple Myeloma; Refractory Multiple Myeloma
• Intervention / Treatment: Drug: carfilzomib; Other: laboratory biomarker analysis; Drug: dexamethasone

Detailed Description

PRIMARY OBJECTIVES:

I. To assess the complete response (CR) rate with carfilzomib and dexamethasone consolidation following an upfront single stem cell transplant (SCT).

SECONDARY OBJECTIVES:

I. To assess the toxicity of carfilzomib and dexamethasone when used as consolidation therapy in patients post SCT.

II. To determine the progression free rate at 1 and 2 years post SCT. III. To evaluate progression-free survival and overall survival.

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:

Patients receive carfilzomib intravenously (IV) over 30 minutes and dexamethasone orally (PO) on days 1, 2, 15, and 16. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up every 3 months for 3 years and then every 6 months for 2 years.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Creatinine =< 3 mg/dL
• Absolute neutrophil count >= 1,000/uL
• Platelet count >= 75,000/uL
• Hemoglobin >= 8.0 g/dL
• Previous diagnosis of symptomatic multiple myeloma (MM)
• Received single autologous stem cell transplantation 60-120 days prior to registration
• Received the autologous SCT =< 12 months of their diagnosis of myeloma to be eligible for the study
• 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)
• Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that the subject may withdraw consent at any time without prejudice to future medical care
• Negative pregnancy test performed =< 7 days prior to registration, for women of childbearing potential only
• Willingness to return to one of the enrolling institutions for follow-up (during the active monitoring phase of the study); 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

• 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
  • 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
• Willing to provide bone marrow and blood samples for correlative research purposes

Exclusion Criteria:

• Prior allogeneic bone marrow/peripheral blood stem cell transplant
• Evidence of disease progression post SCT at the time of consideration for the study enrollment
• Myocardial infarction =< 6 months prior to registration
• New York Heart Association (NYHA) class III or IV heart failure
• Uncontrolled angina
• Severe uncontrolled ventricular arrhythmias
• Electrocardiographic (ECG) evidence of acute ischemia or active conduction system abnormalities; NOTE: prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant
• Seroreactivity for human immunodeficiency virus (HIV), human T-cell lymphotrophic virus (HTLV) I or II, hepatitis B virus (HBV), or hepatitis C virus (HCV)
• Other active malignancy requiring therapy; 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
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (carfilzomib, dexamethasone); Patients receive carfilzomib IV over 30 minutes and dexamethasone PO on days 1, 2, 15, and 16. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.	Drug: carfilzomib; Given IV; Other Names: Kyprolis; PR-171; Other: laboratory biomarker analysis; Correlative studies; Drug: dexamethasone; Given PO; Other Names: Aeroseb-Dex; Decaderm; Decadron; DM; DXM

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of complete response	The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportion will be calculated.	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	The distribution of survival time will be estimated using the method of Kaplan-Meier.	Time from registration to death due to any cause, assessed up to 5 years
Progression-free survival	The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.	Time from registration to progression or death due to any cause, assessed up to 5 years
Time to progression post SCT	The distribution of time to progression will be estimated using the method of Kaplan-Meier.	Time from SCT to the earliest day with documentation of disease progression, assessed at 1 year post-SCT
Time to progression post SCT	The distribution of time to progression will be estimated using the method of Kaplan-Meier.	Time from SCT to the earliest day with documentation of disease progression, assessed at 2 years post-SCT
Maximum grade for each type of adverse event	Frequency tables will be reviewed to determine adverse event patterns.	Up to 30 days after last day of treatment

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: March 14, 2013
• First Submitted That Met QC Criteria: March 14, 2013
• First Posted (Estimate): March 18, 2013

Study Record Updates

• Last Update Posted (Estimate): December 19, 2016
• Last Update Submitted That Met QC Criteria: December 15, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone
• Other Study ID Numbers: MC1287 (Other Identifier: Mayo Clinic); P30CA015083 (U.S. NIH Grant/Contract); NCI-2013-00492 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 12-005975