Phase 1-2 Amrubicin in Combo With Lenalidomide + Weekly Dexamethasone in Relapsed/Refractory Multiple Myeloma

NCT ID: NCT01355705

Last Updated: 2018-09-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-08-31
• Study Completion Date: 2017-07-31

Brief Summary

To assess if amrubicin is safe and useful for patients with multiple myeloma requiring additional treatment.

Detailed Description

PRIMARY OBJECTIVES

• Establish the maximum tolerated dose (MTD) and toxicity profile for the combination of amrubicin with lenalidomide and dexamethasone in previously treated adult patients with multiple myeloma during Phase I
• Determine the combined rate of complete response (CR) and very good partial response (VGPR) for this combination in this population as defined by the International Myeloma Working Group Uniform Response Criteria (IMWGURC)

SECONDARY OBJECTIVES

• Determine the overall response rate (CR, VGPR and PR)
• Assess additional evidence of ant-tumor activity as measured by duration of response (DOR), progression-free survival (PFS), time to tumor progression (TTP), and overall survival (OS)

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Amrubicin + Lenalidomide + Dexamethasone

Amrubicin will be given intravenously on Day 1 of each 3-week cycle beginning with 40 mg/m2, for a maximum of 4 cycles.

Concurrent therapeutic medications:

• Lenalidomide: 10 or 15 mg daily by mouth, Days 1 to 14
• Dexamethasone: 40 mg weekly by mouth (Days 1, 8, and 15)

Other drugs:

• Aspirin: 81 or 325 mg daily oral
• Pegfilgrastim subcutaneous on Day 2

Group Type: EXPERIMENTAL

Amrubicin

Intervention Type: DRUG

40, 60, or 80 mg/m2 intravenous (IV)

Lenalidomide

Intervention Type: DRUG

15 mg daily by mouth

Dexamethasone

Intervention Type: DRUG

40 mg weekly by mouth

Aspirin

Intervention Type: DRUG

81 or 325 mg daily by mouth

Pegfilgrastim

Intervention Type: DRUG

6 mg subcutaneous on Day 2

Interventions

Amrubicin

40, 60, or 80 mg/m2 intravenous (IV)

Intervention Type: DRUG

Lenalidomide

15 mg daily by mouth

Intervention Type: DRUG

Dexamethasone

40 mg weekly by mouth

Intervention Type: DRUG

Aspirin

81 or 325 mg daily by mouth

Intervention Type: DRUG

Pegfilgrastim

6 mg subcutaneous on Day 2

Intervention Type: DRUG

Other Intervention Names

SM-5887; CC-5013; Revlimid; Decadron; Dexamethasone Intensol; Dexpak Taperpak; acetylsalicylic acid; Neulasta; PEG-GCSF

Eligibility Criteria

Inclusion Criteria

• Relapsed or refractory multiple myeloma that has progressed following at least 1 prior therapy.
• Measurable disease defined as one of the following:

• Serum M-protein ≥ 1 g/dL
• Urine M-protein ≥ 200 mg/24 hours
• Received at least 1 prior line of systemic treatment that may have included lenalidomide and/or an anthracycline.
• No cytotoxic chemotherapy within 4 weeks prior to first dose of amrubicin. This interval may be reduced to 14 days for thalidomide, lenalidomide, bortezomib or corticosteroids, provided other entry criteria are met.
• Age ≥ 18 at the time of consent.
• Life expectancy of more than ≥ 3 months.
• No known central nervous system involvement by myeloma.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 at study registration during phase 1. Once safety is confirmed, ECOG performance status 0 to 2 at study registration during phase 2.
• No poorly-controlled intercurrent illness.
• Platelets > 100 x 10^9/L
• Hemoglobin > 8.0g/dL
• Absolute neutrophil count (ANC) >1.5 x 10^9/L
• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 x ULN
• Calculated creatinine clearance ≥ 50 mL/min by Cockcroft-Gault formula.
• Left ventricular ejection fraction (LVEF) ≥ 50% by Echocardiogram (ECHO) or multiple gate acquisition scan (MUGA)
• All study participants must be registered into the mandatory RevAssist program, and be willing and able to comply with the Requirements of RevAssist.
• Disease-free of prior malignancies for ≥ 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast.
• Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 U/mL within 10 to 14 days and again within 24 hours prior to prescribing lenalidomide for Cycle 1 (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin 2 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. FCBP must also agree to ongoing pregnancy testing.
• Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy.
• Ability to understand and the willingness to sign a written informed consent document.
• Able to adhere to the study visit schedule and other protocol requirements.
• Able to take aspirin (81 or ≥ 25 mg) daily as prophylactic anticoagulation. Patients intolerant to aspirin may use warfarin or low molecular weight heparin (LMWH). Patients with previous thromboembolic event on lenalidomide or thalidomide may be started on warfarin or LMWH. Patients already taking warfarin or LMWH do not require additional aspirin..
• Lactating females must agree not to breast-feed while taking lenalidomide

Exclusion Criteria

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
• Pregnant or breastfeeding females.
• Any concurrent severe or uncontrolled medical disease which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
• Use of any other experimental drug or therapy within 28 days of first dose of amrubicin.
• Known hypersensitivity to thalidomide or lenalidomide.
• The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
• LVEF ≤ 50%.
• Concurrent use of other anti-cancer agents or treatments.
• Known positive for HIV, or infectious hepatitis, type B or C.
• Cranial radiotherapy ≤ 21 days prior to first dose of amrubicin; radiotherapy to all other areas ≤ 7 days prior to first dose of amrubicin.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celgene Corporation

INDUSTRY

Sponsor Role: collaborator

Michaela Liedtke

OTHER

Sponsor Role: lead

Responsible Party

Michaela Liedtke

Assistant Professor Medicine/Hematology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Michaela Liedtke

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University School of Medicine

Stanford, California, United States

Countries

United States

References

Dinner S, Dunn TJ, Price E, Coutre SE, Gotlib J, Berube C, Kaufman GP, Medeiros BC, Liedtke M. A phase I, open-label, dose-escalation study of amrubicin in combination with lenalidomide and weekly dexamethasone in previously treated adults with relapsed or refractory multiple myeloma. Int J Hematol. 2018 Sep;108(3):267-273. doi: 10.1007/s12185-018-2468-5. Epub 2018 May 25.

Reference Type: DERIVED

PMID: 29802551 (View on PubMed)

Other Identifiers

AR_MM_PI_007

Identifier Type: OTHER

Identifier Source: secondary_id

SU-05062011-7711

Identifier Type: OTHER

Identifier Source: secondary_id

HEMMYL0018

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-19092

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-19092

Identifier Type: -

Identifier Source: org_study_id