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

NCT01355705 | Completed Phase 1 Results DMC FDA Drug

• 4 other identifiers: IRB-19092AR_MM_PI_007SU-05062011-7711HEMMYL0018
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Response Rates After Amrubicin + Lenalidomide + Dexamethasone, Per International Myeloma Working Group Uniform Response Criteria

  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

  12 weeks

Secondary Outcomes (3)

• Duration of Response (DOR)

  140 days

• Progression-free Survival (PFS)

  9 months

• Time-to-next Treatment

  9 months

Study Arms (1)

Amrubicin + Lenalidomide + Dexamethasone

EXPERIMENTAL

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; Drug: Lenalidomide; Drug: Dexamethasone; Drug: Aspirin; Drug: Pegfilgrastim

Interventions

Amrubicin DRUG

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

Also known as: SM-5887

Amrubicin + Lenalidomide + Dexamethasone

Lenalidomide DRUG

15 mg daily by mouth

Also known as: CC-5013, Revlimid

Amrubicin + Lenalidomide + Dexamethasone

Dexamethasone DRUG

40 mg weekly by mouth

Also known as: Decadron, Dexamethasone Intensol, Dexpak Taperpak

Amrubicin + Lenalidomide + Dexamethasone

Aspirin DRUG

81 or 325 mg daily by mouth

Also known as: acetylsalicylic acid

Amrubicin + Lenalidomide + Dexamethasone

Pegfilgrastim DRUG

6 mg subcutaneous on Day 2

Also known as: Neulasta, PEG-GCSF

Amrubicin + Lenalidomide + Dexamethasone

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Michaela Liedtke: lead
• Celgene Corporation: collaborator

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Related Publications (1)

• 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.

  PMID: 29802551 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

amrubicin; Lenalidomide; Dexamethasone; Calcium Dobesilate; Aspirin; pegfilgrastim

Condition Hierarchy (Ancestors)

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; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Salicylates; Hydroxybenzoates; Phenols

Results Point of Contact

• Title: Michaela Liedtke, MD
• Organization: Stanford University

mliedtke@stanford.edu

650-498-6000

Study Officials

• Michaela Liedtke

  Stanford University

  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 INVESTIGATOR
• PI Title: Assistant Professor Medicine/Hematology

Study Record Dates

• First Submitted: May 16, 2011
• First Posted: May 18, 2011
• Study Start: August 1, 2011
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2017
• Last Updated: September 18, 2018
• Results First Posted: March 3, 2017

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)