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Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With Relapsed or Refractory Multiple Myeloma

Primary Purpose

Refractory Plasma Cell Myeloma

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Paclitaxel Albumin-Stabilized Nanoparticle Formulation

Laboratory Biomarker Analysis

About this trial

This is an interventional treatment trial for Refractory Plasma Cell Myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Absolute neutrophil count >= 500/mm^3
Platelet count >= 25000/mm^3
Hemoglobin >= 6 g/dL
Total bilirubin =< 2.5 X institutional upper limit of normal (ULN)
Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 5 X ULN
Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 5 X ULN
Creatinine =< 3 mg/dL
Patients with relapsed or refractory myeloma who have had >= 3 lines of prior therapy
Measurable disease of multiple myeloma 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
Ability to understand and the willingness to sign a written informed consent document
Negative (serum) pregnancy test done =< 7 days prior to registration, for women of childbearing potential only; NOTE: Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
Willing to return to enrolling institution (Mayo Clinic in Arizona) for follow-up and all study treatments

Exclusion Criteria:

Myelosuppressive therapy for myeloma =< 14 days prior to registration or those who have not recovered from acute reversible adverse events due to agents administered > 21 days earlier
Other concurrent chemotherapy, radiotherapy, or any ancillary therapy considered investigational; NOTE: Bisphosphonates are allowed while on protocol treatment; patients may be receiving stable doses of corticosteroids with a maximum dose of 10 mg of prednisone per day if they are being given for disorders other than lymphoma such as rheumatoid arthritis, polymyalgia rheumatica or adrenal insufficiency, or asthma
Other active malignancy =< 3 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 (i.e. other investigational therapy, anti-neoplastic therapy, etc.) for their cancer
Any of the following:
- Pregnant women or women of reproductive ability who are unwilling to use effective contraception
- Nursing women - NOTE: breastfeeding should be discontinued if the mother is treated with nab-paclitaxel (Abraxane®)
- 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 trial, e.g. uncontrolled infection, uncompensated heart or lung disease
Patients with a >= grade 2 peripheral neuropathy

Sites / Locations

Mayo Clinic in Arizona

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (chemotherapy)

Arm Description

Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Percentage of Patients Who Have a Confirmed Partial Response or Better

A confirmed partial response or better will be considered synonymous with "success" and is defined to be a stringent complete response (sCR = complete response (CR) + Normal serum FLC ratio + Absence of clonal cells in bone marrow), CR (= Negative immunofixation of the serum and urine + <5%plasma cells in bone marrow + Disappearance of any soft tissue plasmacytomas + normalization of FLC ratio), very good partial response (VGPR = partial response (PR) + Serum and urine M-component detectable by immunofixation but not on electrophoresis ), or PR (≥ 50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥ 90% or to <200 mg per 24 h) noted as the objective status on two consecutive evaluations. The percentage of successes (confirmed PR or better) will be estimated by the number of successes divided by the total number of evaluable patients times 100. Confirmed PR or better will be evaluated using all cycles of treatment.

Secondary Outcome Measures

Survival Time

Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.

Progression Free Survival at 3 Months

The distribution of time to progression will be estimated using the method of Kaplan-Meier and the 3 month progression-free rate (percentage) will be provided. Progression is defined as: Any one or more of the following: Increase of 25% from lowest value in: Serum M-component (absolute increase must be ≥ 0.5 g/dl Serum M-component increase ≥ 1 g/dl, if lowest M component was ≥ 5 g/dl Urine M-component (absolute increase must be ≥ 200 mg/24 h) If at on study, the only measurable non-bone marrow parameter was free light chain (FLC), the difference between involved and uninvolved FLC levels (absolute increase must be >10 mg/dl) Bone marrow plasma cell percentage (absolute % must be ≥10%) Or any one or more of the following felt related to the underlying clonal plasma cell proliferative disorder Development of new soft tissue plasmacytomas or bone lesions Hypercalcemia (≥11.5 mg/dl) Decrease in hemoglobin of ≥2 g/dl Serum creatinine level ≥2 mg/dl

Duration of Response of All Evaluable Patients Who Have Achieved a Partial Response or Better

Duration of response is defined for all evaluable patients who have achieved a partial response or better (stringent complete response (sCR = complete response (CR) + Normal serum FLC ratio + Absence of clonal cells in bone marrow), CR (= Negative immunofixation of the serum and urine + <5%plasma cells in bone marrow + Disappearance of any soft tissue plasmacytomas + normalization of FLC ratio), very good partial response (VGPR = partial response (PR) + Serum and urine M-component detectable by immunofixation but not on electrophoresis ), or PR (≥ 50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥ 90% or to <200 mg per 24 h) ) as the date at which the patients earliest best objective status is first noted to be at least a partial response or better to the earliest date of progression is documented. The distribution of duration of response will be estimated using the method of Kaplan-Meier.

Incidence of Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0

Toxicity is defined as a grade 3 or higher adverse events that is classified as either possibly, probably, or definitely related to study treatment. The assignment of attribution to study treatment and grade (or degree of severity) of the adverse event are classified using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. The percentage of patients with a maximum grade 3 or higher adverse event at least possibly related to the study treatment are reported below.

Overall Response Rate

Overall response rate (percentage) is defined as the percentage of patients with a partial response (PR) or better. A PR or better will be considered synonymous with "success" and is defined to be a stringent complete response (sCR = complete response (CR) + Normal serum FLC ratio + Absence of clonal cells in bone marrow), CR (= Negative immunofixation of the serum and urine + <5%plasma cells in bone marrow + Disappearance of any soft tissue plasmacytomas + normalization of FLC ratio), very good partial response (VGPR = PR + Serum and urine M-component detectable by immunofixation but not on electrophoresis ), or PR (≥ 50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥ 90% or to <200 mg per 24 h) noted as the objective status. The percentage of successes (PR or better) will be estimated by the number of successes divided by the total number of evaluable patients times 100. PR or better will be evaluated using all cycles of treatment.

Full Information

NCT ID

NCT01646762

First Posted

June 19, 2012

Last Updated

September 14, 2017

Sponsor

Mayo Clinic

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT01646762

Brief Title

Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With Relapsed or Refractory Multiple Myeloma

Official Title

Phase II Trial of Nab-paclitaxel (Abraxane®) in Patients With Relapsed or Refractory Multiple Myeloma

Study Type

Interventional

2. Study Status

Record Verification Date

December 2016

Overall Recruitment Status

Terminated

Why Stopped

Did not pass the Stage 1 interim analysis.

Study Start Date

November 5, 2012 (undefined)

Primary Completion Date

January 15, 2015 (Actual)

Study Completion Date

October 27, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Mayo Clinic

Collaborators

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This phase II trial studies how well paclitaxel albumin-stabilized nanoparticle formulation works in treating patients with multiple myeloma that has returned or did not respond to treatment. Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Detailed Description

PRIMARY OBJECTIVES: I. To evaluate the efficacy (overall response rate) of single agent nab-paclitaxel (Abraxane) (paclitaxel albumin-stabilized nanoparticle formulation) in patients with relapsed or refractory multiple myeloma. SECONDARY OBJECTIVES: I. To evaluate the adverse events associated with use of single agent nab-paclitaxel (Abraxane) in patients with relapsed or refractory multiple myeloma. II. To evaluate overall survival, time to progression, and duration of response among patients with relapsed or refractory multiple myeloma undergoing treatment with single agent nab-paclitaxel (Abraxane). OUTLINE: Patients receive paclitaxel albumin-stabilized nanoparticle formulation intravenously (IV) over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3-6 months for up to 3 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Refractory Plasma Cell Myeloma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

13 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment (chemotherapy)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Paclitaxel Albumin-Stabilized Nanoparticle Formulation

Other Intervention Name(s)

ABI 007, ABI-007, Abraxane

Intervention Description

Given IV

Intervention Type

Other

Intervention Name(s)

Laboratory Biomarker Analysis

Intervention Description

Correlative studies

Primary Outcome Measure Information:

Title

Percentage of Patients Who Have a Confirmed Partial Response or Better

Description

Time Frame

Up to 3 years

Secondary Outcome Measure Information:

Title

Survival Time

Description

Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.

Time Frame

Time from registration to death due to any cause, assessed up to 3 years

Title

Progression Free Survival at 3 Months

Description

Time Frame

Time from registration to the earliest date of documentation of disease progression, assessed up to 3 years

Title

Duration of Response of All Evaluable Patients Who Have Achieved a Partial Response or Better

Description

Time Frame

Date at which the patient's earliest best objective status is first noted to be at least a partial response or better to the earliest date progression is documented, assessed up to 3 years

Title

Incidence of Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0

Description

Time Frame

Up to 3 years

Title

Overall Response Rate

Description

Time Frame

Up to 3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Absolute neutrophil count >= 500/mm^3 Platelet count >= 25000/mm^3 Hemoglobin >= 6 g/dL Total bilirubin =< 2.5 X institutional upper limit of normal (ULN) Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 5 X ULN Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 5 X ULN Creatinine =< 3 mg/dL Patients with relapsed or refractory myeloma who have had >= 3 lines of prior therapy Measurable disease of multiple myeloma 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 Ability to understand and the willingness to sign a written informed consent document Negative (serum) pregnancy test done =< 7 days prior to registration, for women of childbearing potential only; NOTE: Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately Willing to return to enrolling institution (Mayo Clinic in Arizona) for follow-up and all study treatments Exclusion Criteria: Myelosuppressive therapy for myeloma =< 14 days prior to registration or those who have not recovered from acute reversible adverse events due to agents administered > 21 days earlier Other concurrent chemotherapy, radiotherapy, or any ancillary therapy considered investigational; NOTE: Bisphosphonates are allowed while on protocol treatment; patients may be receiving stable doses of corticosteroids with a maximum dose of 10 mg of prednisone per day if they are being given for disorders other than lymphoma such as rheumatoid arthritis, polymyalgia rheumatica or adrenal insufficiency, or asthma Other active malignancy =< 3 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 (i.e. other investigational therapy, anti-neoplastic therapy, etc.) for their cancer Any of the following: Pregnant women or women of reproductive ability who are unwilling to use effective contraception Nursing women - NOTE: breastfeeding should be discontinued if the mother is treated with nab-paclitaxel (Abraxane®) 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 trial, e.g. uncontrolled infection, uncompensated heart or lung disease Patients with a >= grade 2 peripheral neuropathy

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Rafael Fonseca

Organizational Affiliation

Mayo Clinic

Official's Role

Principal Investigator

Facility Information:

Facility Name

Mayo Clinic in Arizona

City

Scottsdale

State/Province

Arizona

ZIP/Postal Code

85259

Country

United States

12. IPD Sharing Statement

Learn more about this trial

Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With Relapsed or Refractory Multiple Myeloma

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