Phase I/II Trial of the Combination of Lenalidomide (Revlimid) and Nab-paclitaxel (Abraxane) in the Treatment of Relapsed/Refractory Multiple Myeloma

NCT02075021 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: 12-02519
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators will perform a phase I/II trial of Revlimid daily for 21 days and Abraxane weekly for 3 weeks. Accrual will be on standard cohorts of 3 patients. Once the maximum toxicity dose (MTD) is reached, the level below will be expanded to 25 patients for a pilot phase II trial. All treatments will be performed until progression. Assessments will be made at least at the 2, 4 and 6 month timepoints and monthly thereafter until progression. The purpose of this research study is to determine how much of the combination of Revlimid and Abraxane can be given safely and how well they work together against the cancer. Currently, this trial is in the phase 1 stage.

Conditions

Relapsed or Refractory Multiple Myeloma

Keywords

relapsed; refractory; multiple myeloma; revlimid; lenalidomide; abraxane; n-paclitaxel

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (Phase I)

  Dose limiting toxicity will be accessed based on Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

  4 weeks

Secondary Outcomes (1)

• the Number of Patients Who Achieve Complete Response (CR) or Partial Response (PR) (Phase II)

  up to 2 years

Study Arms (1)

lenalidomide and nab-paclitaxel

EXPERIMENTAL

100 mg/m\^2 of Abraxane weekly for 3 weeks and 10 mg Revlimid daily for 21 days, with a dose escalation for Revlimid to 15 mg and to 25 mg. One cycle is 4 weeks. Dose de-escalations will also be performed for both drugs as necessary. Patients will be treated until disease progression.

Drug: Lenalidomide; Drug: nab-paclitaxel

Interventions

Lenalidomide DRUG

Also known as: Revlimid

lenalidomide and nab-paclitaxel

nab-paclitaxel DRUG

Also known as: Abraxane

lenalidomide and nab-paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with relapsed/refractory multiple myeloma based on standard criteria
• Renal function assessed by calculated creatinine clearance as follows
• Phase I subjects must have calculated creatinine clearance \>=30ml/min by Cockcroft-Gault formula.
• Phase II subjects must have calculated creatinine clearance \>=30ml/min by Cockcroft-Gault formula.
• Progressed (\>25% increase in evaluable disease) or non response on Revlimid or within 60 days of stopping Revlimid
• \> 1 prior regimen
• Total bilirubin \<=1.5 x Upper limit of normal (ULN)
• AST (aspartate aminotransferase) or serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) or serum glutamic-pyruvic transaminase (SGPT) \<=3 x ULN.
• All study participants must be registered into the mandatory Revlimid REMS® program, and be willing and able to comply with the requirements of Revlimid REMS®.
• Females of childbearing potential must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL (milli-International unit/milliliter) within 10 - 14 days and again within 24 hours prior to prescribing lenalidomide for Cycle 1 (prescriptions must be filled within 7 days as required by Revlimid REMS) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide.
• Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA (acetylsalicylic acid) may use warfarin or low molecular weight heparin).
• With \< or = grade 2 neuropathy
• Karnofsky performance status ≥ 50
• Patients treated with local radiotherapy with or without a brief (2 weeks or less) exposure to steroids are eligible. Patients who require concurrent radiotherapy should have entry to the protocol deferred until the radiotherapy is completed
• Meets the following pretreatment laboratory criteria at Baseline (Day 1 of Cycle 1, before study drug administration)

You may not qualify if:

• \> grade 2 neuropathy
• \> Cr (complete response) 2.5
• LFTs (liver function test) \> 2x nl (normal limit)
• Patient had myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG (electrocardiogram) abnormality at screening must be documented by the investigator as not medically relevant.
• Known hypersensitivity to thalidomide or Revlimid (if applicable).
• The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
• Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine are eligible.
• Female subject is pregnant or lactating. Confirmation that the subject is not pregnant must be established by a negative serum -human chorionic gonadotropin (hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for postmenopausal or surgically sterilized women.
• Female patients who are lactating or have a positive serum pregnancy test during the screening period, or a positive urine pregnancy test on Day 1 before first dose of study drug, if applicable.
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
• Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial.
• Radiation therapy within 3 weeks before randomization. Enrollment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy.
• POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein) and skin changes)
• Plasma cell leukemia

Sponsors & Collaborators

• NYU Langone Health: lead
• Celgene Corporation: collaborator

Study Sites (1)

NYU School of Medicine

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Recurrence; Multiple Myeloma

Interventions

Lenalidomide; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Amitabha Mazumder, MD
• Organization: NYU Clinical Cancer Center

Amitabha.Mazumder@nyumc.org

(212) 731-5757

Study Officials

• Amitabha Mazumder, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2014
• First Posted: March 3, 2014
• Study Start: March 1, 2014
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: October 15, 2018
• Results First Posted: September 5, 2017

Record last verified: 2018-09

Locations

US (1)