Open-label Study of LCL161 Alone or With Cyclophosphamide in Relapsed/Refractory Multiple Myeloma
This phase II trial studies how well Inhibitor of Apoptosis Proteins (IAP) antagonist LCL161 [also known as Second Mitochondria-derived Activator of Caspases (SMAC) mimetic LCL161] alone or with cyclophosphamide works in treating patients with relapsed or refractory multiple myeloma. Immunomodulatory therapies, such as LCL161, may stimulate the immune system in different ways to kill the cancer cells. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing, and can also help to modulate the immune response to cancer. It is not yet known whether giving LCL161 alone or with cyclophosphamide is more effective in treating multiple myeloma.
Multiple Myeloma in Relapse
Refractory Plasma Cell Neoplasm
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of LCL161 Alone and in Combination With Cyclophosphamide in Patients With Relapsed or Refractory Multiple Myeloma.|
- Proportion of confirmed overall responses [stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR)] with single agent LCL161 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. 95% confidence intervals for the true success proportion will be calculated by the exact binomial method.
- Confirmed overall response rate with the addition of cyclophosphamide [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]Will be estimated by the number of patients who achieve a confirmed overall response at any time (with single agent LCL161 or LCL161 plus cyclophosphamide) divided by the number of evaluable patients. 95% confidence intervals for the true confirmed overall response rate will be calculated by the exact binomial method.
- Overall survival [ Time Frame: From registration to death due to any cause, assessed up to 1 year ] [ Designated as safety issue: No ]The distribution of survival time will be estimated using the method of Kaplan-Meier.
- Event-free survival [ Time Frame: From registration to disease progression while receiving LCL161 and cyclophosphamide, death due to any cause, or subsequent treatment for multiple myeloma, assessed up to 1 year ] [ Designated as safety issue: No ]The distribution of event-free survival will be estimated using the method of Kaplan-Meier.
- Incidence of adverse events graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 30 days ] [ Designated as safety issue: Yes ]The maximum grade for each type of adverse event, regardless of causality, will be recorded and reported for each patient, and frequency tables will be reviewed to determine adverse event patterns.
|Study Start Date:||October 2013|
|Estimated Study Completion Date:||October 2017|
|Estimated Primary Completion Date:||October 2015 (Final data collection date for primary outcome measure)|
Patients receive LCL161 PO QD on days 1, 8, 15, and 22. Patients lacking a minor response by end of course 2 or partial response by end of course 4 also receive cyclophosphamide PO QD on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other Names:Drug: cyclophosphamide
I. To evaluate the confirmed overall response rate (>= partial response [PR]) to LCL161, used as a single agent, in patients with relapsed multiple myeloma (MM).
I. To estimate the confirmed overall response rate to LCL161 in combination with cyclophosphamide, when cyclophosphamide is added to LCL161 for lack of response or progression.
II. To estimate the overall survival and event-free survival of patients treated with LCL161 in combination with cyclophosphamide, when cyclophosphamide is added to LCL161 for lack of response or progression.
III. To evaluate the tolerability of LCL161 alone and in combination with cyclophosphamide in patients with relapsed MM.
I. To determine degradation of cellular inhibitor of apoptosis protein-1 (cIAP1) in peripheral blood mononuclear cells (PBMC), changes in serum cytokines, and changes in immune cell subsets by flow cytometry.
II. To correlate the effect of LCL161 with the presence of activating mutations of the nuclear factor kappa beta (NFKB) pathway.
III. To evaluate the pharmacokinetics (PK) of LCL161 alone, and LCL161 in combination with cyclophosphamide.
Patients receive LCL161 orally (PO) once daily (QD) on days 1, 8, 15, and 22. Patients lacking a minor response by end of course 2 or partial response by end of course 4 also receive cyclophosphamide PO QD on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 1 year.
|Contact: Mayo Clinic Clinical Trials Office||507-538-7623|
|United States, Arizona|
|Mayo Clinic in Arizona||Not yet recruiting|
|Scottsdale, Arizona, United States, 85259|
|Principal Investigator: Peter L. Bergsagel, M.D.|
|United States, Florida|
|Mayo Clinic in Florida||Not yet recruiting|
|Jacksonville, Florida, United States, 32224-9980|
|Principal Investigator: Asher A. Chanan-Khan, M.D.|
|United States, Minnesota|
|Mayo Clinic||Not yet recruiting|
|Rochester, Minnesota, United States, 55905|
|Principal Investigator: Yi Lin, M.D., Ph.D.|
|Study Chair:||Peter L. Bergsagel, M.D.||Mayo Clinic campus in Arizona|
|Principal Investigator:||Asher Chanan-Khan, M.D.||Mayo Clinic campus in Florida|