Carfilzomib + High Dose Melphalan as Preparative Regimen for Autologous Hematopoietic Stem Cell Transplantation

• Status: Completed
• Trial end date: 2017-11-01
• Target enrollment: 0
• Participant gender: All

Summary

This study is for patients that have multiple myeloma that has come back or relapsed and their condition indicates a procedure called an Autologous Hematopoietic Stem Cell Transplantation (AHSCT). AHSCT is a procedure when stem cells from bone marrow or blood are removed before high-dose chemotherapy. Afterwards, the removed stem cells are put back into the patient's body to form a new population of blood cells.

The high-dose chemotherapy administered before the AHSCT is called "Conditioning Therapy." The FDA has approved the use of the drug melphalan as a conditioning therapy. This research study will look at whether adding the study drug called carfilzomib will improve participant outcomes. Carfilzomib is considered investigational and is not approved by the FDA for the treatment of relapsed multiple myeloma.

This study is divided into two phases.

Phase I: Dose Escalation Phase:

The main purpose of Part I of this study is to examine the safety of the study drug, carfilzomib, and determine the safest amount of the study drug that can be given to subjects who have multiple myeloma. Subjects on this study will receive different dose levels of the study drug. If you are one of the first three subjects to receive the study drug, it will be at what is called the 'starting dose' for the study which is the lowest dose that is expected to be tolerated based on prior research. After the first set of participants receive the study drug, the study doctor will review their health to see how they are tolerating the treatment. This will decide if the study drug dosage will be increased or decreased for the next set of subjects who join the study. It is anticipated that 12- 18 participants will enroll in the Phase I portion of this study.

Phase II: Safety Confirmation Phase:

Once the study doctor has discovered the highest possible dose of study drug that subjects can tolerate, up to 28 more subjects may be enrolled at that dose level. The main purpose of the Phase II portion of the study is look at how effective the combination of carfilzomib and melphalan when given before your stem cell transplantation is in treating multiple myeloma. This expansion phase will also include evaluation of two single agent carfilzomib maintenance therapy regimens for patients without disease progression at day 100.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Alabama at Birmingham
• Collaborators: Amgen; Onyx Pharmaceuticals
• Treatments: Melphalan

Criteria

Inclusion Criteria:

1. Age ≥ 18 years and ≤ 70 years

2. Life expectancy ≥ 12 months

3. Eastern Cooperative Oncology Group (ECOG) performance status 0-2

4. Diagnosis of symptomatic multiple myeloma, relapsed after initial therapy.

5. At least minimal response (defined as 25% decrease in the M protein in serum or urine) to the most recent treatment regimen.

6. Evaluable disease prior to most recent treatment regimen as defined by at least one of the following:

• Serum monoclonal (M) protein ≥0.5 g/dl by protein electrophoresis

• 200 mg of M 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

• Monoclonal bone marrow plasmacytosis ≥30%

7. Adequate hepatic function, with serum ALT ≤ 3.5 times the upper limit of normal and serum direct bilirubin ≤ 2 mg/dL (34 µmol/L) within 14 days prior to start of therapy

8. Hemoglobin ≥ 8 g/dL (80 g/L) within 14 days prior to registration (subjects may be receiving red blood cell [RBC] transfusions in accordance with institutional guidelines)

9. Creatinine clearance (CrCl) ≥ 40 mL/minute within 14 days prior to registration, either measured or calculated using a standard formula (eg, Cockcroft and Gault).

10. Prior storage of at least 2 x 106 CD34+ cells/kg available for autologous transplantation. During the phase 1 component of the study, at least the same amount of cells is required as "back up" in the unlikely event of non-engraftment.

11. Subjects may have had a prior AHSCT for the treatment of MM as long as it was performed greater than 12 months from study registration.

12. Subjects must meet institutional general eligibility criteria for autologous transplantation.

13. Written informed consent in accordance with federal, local, and institutional guidelines.

14. Female of childbearing potential (FCBP) must agree to ongoing pregnancy testing and to practice contraception.

15. Male subjects must agree to practice contraception.

Exclusion Criteria:

1. Pregnant or lactating females.

2. Major surgery within 30 days prior to start of treatment.

3. Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to registration.

4. Known human immunodeficiency virus infection.

5. Active hepatitis B or C infection.

6. Unstable angina or 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.

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

8. Nonhematologic malignancy within the past 3 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen levels; or d) 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 tumors of the adrenal or pancreas.

9. Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to registration.

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

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

12. 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.