Phase I/II Amrubicin in Combo With Lenalidomide + Weekly Dexamethasone in Relapsed/Refractory Multiple Myeloma

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by Stanford University
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Michaela Liedtke, Stanford University
ClinicalTrials.gov Identifier:
NCT01355705
First received: May 16, 2011
Last updated: September 20, 2013
Last verified: September 2013
  Purpose

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)

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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II 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 Stanford University:

Primary Outcome Measures:
  • 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 [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
  • Determine the combined rate of complete response (CR) and very good partial response (VGPR) for this combination in this population based on the modified International Myeloma Working Group Uniform Response Criteria. [ Time Frame: 21, 42, 63, 84 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Determine the overall response rate (CR, VGPR and PR) [ Time Frame: 84 days ] [ Designated as safety issue: No ]
  • Assess additional evidence of ant-tumor activity as measured by duration of response (DOR), progression-free survival (PFS), and time to tumor progression (TTP) [ Time Frame: 84 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 42
Study Start Date: August 2011
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Amrubicin
Amrubicin will be given intravenously on Day 1 of each 3 week cycle beginning with 40 mg/m2. One cycle is defined as 3 weeks. The maximum treatment period is 4 cycles.
Drug: Amrubicin
40, 60, or 80 mg/m2; iv
Other Name: SM-5887
Drug: Lenalidomide
10 or 15 mg daily; po
Other Names:
  • CC-5013
  • Revlimid
Drug: Dexamethasone
40 mg weekly; po
Other Names:
  • Decadron
  • Dexamethasone Intensol
  • Dexpak Taperpak
Drug: Aspirin
81 or 325 mg daily; po
Other Name: acetylsalicylic acid

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The patient has relapsed or refractory multiple myeloma that has progressed following at least one (1) prior therapy.
  • The patient has measurable disease defined as one of the following:

serum M-protein >=1 g/dL urine M-protein >=200 mg/24 hours

  • Must have received at least one (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. NOTE: 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.
  • The patient has a life expectancy of more than >= months.
  • No known central nervous system involvement by myeloma.
  • ECOG performance status 0-1 at study registration during phase I. Once safety is confirmed, ECOG performance status 0-2 at study registration during phase II.
  • No poorly controlled intercurrent illness.
  • Platelets >100 x 10^9/L, Hemoglobin > 8.0g/dL and ANC >1.5 x 10^9/L
  • AST and ALT <= 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 "insitu" 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 mIU/mL within 10 - 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 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. 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. See Appendix: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods.
  • 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 ASA 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.

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. (Lactating females must agree not to breast feed while taking lenalidomide).
  • 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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01355705

Contacts
Contact: Vani Jain (650) 725-5459 vani@stanford.edu

Locations
United States, California
Stanford University School of Medicine Recruiting
Stanford, California, United States, 94305
Contact: Vani Jain    650-725-5459    vani@stanford.edu   
Contact: Cancer Clinical Trials Office    (650) 498-7061    ccto-office@stanford.edu   
Principal Investigator: Michaela Liedtke         
Sub-Investigator: Steven Edward Coutre         
Sub-Investigator: Bruno Carneiro de Medeiros         
Sponsors and Collaborators
Michaela Liedtke
Celgene Corporation
Investigators
Principal Investigator: Michaela Liedtke Stanford University
  More Information

No publications provided

Responsible Party: Michaela Liedtke, Assistant Professor Medicine/Hematology, Stanford University
ClinicalTrials.gov Identifier: NCT01355705     History of Changes
Other Study ID Numbers: HEMMYL0018, AR_MM_PI_007, SU-05062011-7711, 19092
Study First Received: May 16, 2011
Last Updated: September 20, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

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
Aspirin
Dexamethasone acetate
Dexamethasone
BB 1101
Dexamethasone 21-phosphate
Amrubicin
Lenalidomide
Thalidomide
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on July 20, 2014