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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01355705
First Posted: May 18, 2011
Last Update Posted: May 30, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Michaela Liedtke, Stanford University
  Purpose
To assess if amrubicin is safe and useful for patients with multiple myeloma requiring additional treatment.

Condition Intervention Phase
Multiple Myeloma Drug: Amrubicin Drug: Lenalidomide Drug: Dexamethasone Drug: Aspirin Drug: Pegfilgrastim Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of Amrubicin in Combination With Lenalidomide and Weekly Dexamethasone in Relapsed/Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Michaela Liedtke, Stanford University:

Primary Outcome Measures:
  • Response Rates After Amrubicin + Lenalidomide + Dexamethasone, Per International Myeloma Working Group Uniform Response Criteria [ Time Frame: 12 weeks ]

    Modified International Myeloma Working Group Uniform Response Criteria:

    Complete (CR)=

    • Negative for monoclonal protein (MP) in urine (U) and serum (S) +
    • No tissue plasmacytomas (PC) +
    • <5% plasma cells (PCs) in marrow (M)

    Stringent CR (sCR)= CR with normal light chain ratio+ no PCs in M

    Near CR (nCR)= CR, except MP persists in U and S

    Partial (PR)= S MP ≤50%, + U MP ≤90% or <200 mg/24 hours (hr)

    Very Good PR (VGPR)= in S MP ≤90%, + U MP <100 mg/24 hr

    Minimal (MR)=

    • S MP ≤51-75%, +
    • If light chain is excreted, reduced 50-89%/24 hr that is also >200 mg/24 hr, +
    • No increase in lytic bone lesions

    Progressive disease (PD)= any of:

    • S MP ≥125% and/or ≥+0.5 g/dL,
    • U MP ≥125% and/or ≥+200 mg/24 hr
    • New or increased bone lesions/PC
    • S calcium >11.5 mg/dL (attributed to increased PCs)

    PD after CR/sCR=

    • Reappearance of S or U MP
    • ≥5% clonal PCs in M
    • New PC, lytic bone lesions, hypercalcemia

    Stable Disease (SD)= Not CR, VGPR, MR, PR, or PD



Secondary Outcome Measures:
  • Duration of Response (DOR) [ Time Frame: 140 days ]
  • Progression-free Survival (PFS) [ Time Frame: 9 months ]

    Progression-free survival (PFS) is alive and free from progression, per the modified International Myeloma Working Group Uniform Response Criteria, defined as any of:

    • Serum monoclonal protein ≥ 125% baseline and/or ≥ +0.5 g/dL from baseline,
    • Urine monoclonal protein ≥ 125% baseline and/or ≥ +200 mg/24 hour from baseline
    • New or increased bone lesions or plasmacytomas
    • Serum calcium > 11.5 mg/dL (attributed to increased plasma cells)

  • Time-to-next Treatment [ Time Frame: 9 months ]

Enrollment: 14
Study Start Date: August 2011
Estimated Study Completion Date: July 2017
Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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
Drug: Amrubicin
40, 60, or 80 mg/m2 intravenous (IV)
Other Name: SM-5887
Drug: Lenalidomide
15 mg daily by mouth
Other Names:
  • CC-5013
  • Revlimid
Drug: Dexamethasone
40 mg weekly by mouth
Other Names:
  • Decadron
  • Dexamethasone Intensol
  • Dexpak Taperpak
Drug: Aspirin
81 or 325 mg daily by mouth
Other Name: acetylsalicylic acid
Drug: Pegfilgrastim
6 mg subcutaneous on Day 2
Other Names:
  • Neulasta
  • PEG-GCSF

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)
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01355705


Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Michaela Liedtke
Celgene Corporation
Investigators
Principal Investigator: Michaela Liedtke Stanford University
  More Information

Responsible Party: Michaela Liedtke, Assistant Professor Medicine/Hematology, Stanford University
ClinicalTrials.gov Identifier: NCT01355705     History of Changes
Other Study ID Numbers: IRB-19092
AR_MM_PI_007 ( Other Identifier: Celgene Corporation )
SU-05062011-7711 ( Other Identifier: Stanford University )
HEMMYL0018 ( Other Identifier: OnCore )
First Submitted: May 16, 2011
First Posted: May 18, 2011
Results First Submitted: January 11, 2017
Results First Posted: May 30, 2017
Last Update Posted: May 30, 2017
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Aspirin
Lenalidomide
Amrubicin
Thalidomide
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists