DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more



Ph 1b, Carfilzomib, Bendamustine, Dexamethasone in Multiple Myeloma

Information source: M.D. Anderson Cancer Center
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Myeloma

Intervention: Carfilzomib (Drug); Bendamustine (Drug); Dexamethasone (Drug)

Phase: Phase 1

Status: Recruiting

Sponsored by: M.D. Anderson Cancer Center

Official(s) and/or principal investigator(s):
Michael Wang, MD,MS, Principal Investigator, Affiliation: M.D. Anderson Cancer Center

Overall contact:
Michael Wang, MD,MS, Phone: 713-792-2860

Summary

The goal of this clinical research study is to find the highest tolerable dose of carfilzomib when given in combination with bendamustine and dexamethasone. The safety of this drug combination will also be studied.

Clinical Details

Official title: A Single Center Phase Ib Study of Carfilzomib, Bendamustine and Dexamethasone in Subjects With Relapsed/Refractory Multiple Myeloma

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Maximum Tolerated Dose (MTD) of Carfilzomib in Combination with Bendamustine and Dexamethasone

Secondary outcome: Overall Response

Detailed description: Study Groups: If you are found to be eligible to take part in this study, you will be assigned to a dose level of carfilzomib based on when you joined this study. Up to 5 dose levels of carfilzomib in combination with bendamustine and dexamethasone will be tested. Up to 3-6 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level of both carfilzomib and bendamustine. The second, third,, and fourth groups will receive higher doses of carfilzomib. The fifth and final group will receive a higher dose of bendamustine. The study will continue to move from group to group only if no intolerable side effects are seen in the previous groups. All participants will receive the same dose level of dexamethasone. Study Drug Administration: Each study cycle is 28 days. You will receive carfilzomib by vein over 30 minutes on Days 1, 2, 8, 9, 15, and 16 of Cycles 1-12, and on Days 1, 2, 15, and 16 of Cycles 13 and beyond. The infusion will last about 30 minutes. You may remain on the Cycle 1-12 dosing schedule for the entire study if the doctor thinks it is in your best interest. You will be monitored by the study staff for any side effects for at least 1 hour after receiving carfilzomib during each dose you receive during Cycle 1 and on Day 1 of Cycle 2. You will receive bendamustine by vein right after your carfilzomib infusion on Days 1 and 2 of Cycles 1-3 and Day 1 of Cycle 4 and each cycle after that. The infusion will last about 1 hour. You will take dexamethasone by mouth or by vein (over 20 minutes) at the following times:

- On Days 1, 2, 8, 9, 15, 16, 22, and 23 of Cycles 1-3.

- On Days 1, 2, 15 and 16 of Cycles 4-12.

- On Days 1 and 2 of Cycles 13 and beyond.

Dexamethasone should be taken 30 minutes to 4 hours before the carfilzomib dose on the days you receive carfilzomib. If you are taking dexamethasone by mouth, it should be taken with food and a glass of water. Study Visits: On Day 1 of Cycles 1-12, the following tests and procedures will be performed:

- You will have a physical exam, including a neurologic exam.

- Blood (about 2 teaspoons) and urine will be collected for routine tests. This routine

blood draw will include a pregnancy test for women who are able to become pregnant.

- Blood (about 3-4 teaspoons) and urine will be collected to check the status of the

disease.

- You will collect your urine over 24 hours to measure your protein levels. You will be

given a container for collecting the urine. On Days 2, 8 and 15 of Cycles 1-12, the following tests and procedures will be performed:

- Blood (about 2 teaspoons) will be drawn for routine tests.

On Day 1 of Cycle 13 and each cycle after that, the following tests and procedures will be performed:

- You will have a physical exam.

- Blood (about 2 teaspoons) will be drawn for routine tests. This routine blood draw will

include a pregnancy test for women who are able to become pregnant.

- Blood (about 3-4 teaspoons) and urine will be collected to check the status of the

disease.

- You will collect your urine over 24 hours to measure your protein levels. You will be

given a container for collecting the urine. On Day 15 of Cycles 13 and each cycle after that, the following tests and procedures will be performed:

- Blood (about 2 teaspoons) will be drawn for routine tests.

Length of Study: You may continue taking the study drugs for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions. Your participation in this study will be over after you have completed the end-of-study and follow-up visits. End-of-Study Visit: Within 30 days after you have stopped receiving the study drugs, you will have an end-of-study visit. At this visit, the following tests and procedures will be performed:

- You will have a physical exam.

- Blood (about 2 teaspoons) will be drawn for routine tests. This routine blood draw will

include a pregnancy test for women who are able to become pregnant.

- Blood (about 3-4 teaspoons) and urine will be collected to check the status of the

disease.

- You will collect your urine over 24 hours to measure your protein levels. You will be

given a container for collecting the urine.

- If the doctor thinks it is necessary, you will have a CT scan or MRI scan to look for

tumors caused by MM. Follow-Up: If you leave the study and the disease did not get worse while you were on study, the study staff will call you every 3 months for 1 year and every 6 months every year after that to ask you about the status of the disease. The phone call will last about 5 minutes. Additional Information: In order to decrease the risk of a possible side effect from carfilzomib called tumor lysis syndrome (TLS), you will be asked to make sure you are well-hydrated by drinking at least 6-8 cups (about 64 ounces) of water per day starting 2 days before your first study drug infusion. The study staff will tell you how many days you will need to drink this fluid. During each dose of Cycle 1 and on Day 1 of Cycle 2, you will receive fluids by vein before and after each dose of carfilzomib. If you think you have an infection, cold, flu, fever, and/or cough, if you have been exposed to a person with these types of conditions or illnesses, or if you have been asked to take antibiotics or antivirals at any time during the study, you should tell the study doctor right away. This is an investigational study. Carfilzomib is FDA approved and commercially available for the treatment of certain types of MM. Its use in this study is investigational. Bendamustine is FDA approved and commercially available for the treatment of rituximab-refractory Non-Hodgkin's Lymphoma, slow-growing (indolent) lymphoma, and for chronic lymphocytic leukemia (CLL). Its use in this study is investigational. Dexamethasone is FDA approved and commercially available in combination with lenalidomide for the treatment of patients with MM who have received at least 1 prior therapy. Its use in combination with carfilzomib and bendamustine is investigational. The study doctor can explain how the study drugs are designed to work. Up to 49 participants will be enrolled in this study. All will be enrolled at MD Anderson.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria: 1. Relapsed and or refractory multiple myeloma after at least one prior line of therapy. There is no upper limit of prior lines of therapy. Patients who are ineligible for stem cell transplantation are allowed. Patients should have received at least one prior novel agent (Immunomodulatory agents or proteasome inhibitors). Patients eligible for bone marrow transplant must have undergone BMT prior to enrollment. 2. Measurable disease, as defined by one or both of the following (assessed within 30 days prior to initiation of therapy): a. Serum M-protein >/= 0. 5 g/d; b. Urine Bence-Jones protein >/= 200 mg/24 hours. 3. Patients with light chain only myeloma are eligible. The involved free light chain level >/= 100 mg/L with abnormal serum free light chain ratio. 4. Documented relapse or progressive disease on or after any regimen (subjects refractory to the most recent regimen are eligible) 5. Primary refractory patients (never responded to any therapy) are eligible 6. Age >/= 18 years

7. Eastern Cooperative Oncology Group performance status 0 - 2

8. Adequate hepatic function, with serum ALT < 3. 5 times the upper limit of normal and serum direct bilirubin < 2 mg/dL (34 Omol/L) within 30 days prior to Cycle 1 Day 1. 9. Absolute neutrophil count (ANC) >/= 1. 0 × 10^9/L within 30 days prior to Cycle 1 Day 1, without granulocyte-colony stimulating factor (G-CSF). 10. Hemoglobin > 9 g/dL (80 g/L) within 30 days prior to Cycle 1 Day 1 (subjects may be receiving red blood cell transfusions in accordance with institutional guidelines) 11. Platelet count > 100 × 10^9/L ( 30 × 10^9/L if myeloma involvement in the bone marrow aspirate is > 50%) within 30 days prior to Cycle 1 Day 1. Subjects may receive platelet transfusions within institutional guidelines. 12. Creatinine clearance > 50 mL/minute within 30 days prior to Cycle 1 Day 1, either measured or calculated using a standard formula. Patient should have a normalized or normal uric acid level prior to study entry. 13. Written informed consent in accordance with federal, local, and institutional guidelines 14. Females of childbearing potential must have a negative pregnancy test and agree to ongoing pregnancy testing and to practice contraception. (Birth control methods should be determined in consultation with the investigator). 15. Male subjects must agree to practice contraception. Exclusion Criteria: 1. Intolerance to previous bendamustine, carfilzomib or dexamethasone or mannitol; subjects who are allergic to bortezomib are not excluded 2. Chemotherapy (approved or investigational) within 3 weeks prior to the first day of treatment or antibody therapy within 6 weeks prior to the first day of treatment. 3. Radiotherapy to >/= 3 sites at the same time within 1 week prior to the first day of treatment. 4. Immunomodulatory therapy such as Imids or stem cell transplant within 28 days prior to the first day of treatment. 5. Pregnant or lactating females 6. Major surgery within 21 days prior to the first day of treatment. 7. Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to the first day of treatment. 8. Known human immunodeficiency virus infection 9. Known Active hepatitis B or C infection 10. Unstable angina or myocardial infarction within 4 months prior to the first day of treatment, The New York Heart Association (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 11. Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to the first day of treatment. 12. Non-hematologic 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

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

the first day of treatment. 14. Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib) 15. Contraindication to any of the required concomitant drugs or supportive treatments or intolerance to hydration due to preexisting pulmonary or cardiac impairment 16. Subjects with known or likely systemic amyloidosis 17. Ongoing graft-vs-host disease 18. Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to the first day of treatment. 19. 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

Locations and Contacts

Michael Wang, MD,MS, Phone: 713-792-2860

University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States; Recruiting
Additional Information

University of Texas MD Anderson Cancer Center Website

Starting date: April 2014
Last updated: July 27, 2015

Page last updated: August 23, 2015

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017