Trial Outcomes & Findings for Phase 1-2 Amrubicin in Combo With Lenalidomide + Weekly Dexamethasone in Relapsed/Refractory Multiple Myeloma (NCT NCT01355705)

Last Updated: 2018-09-18

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

14 participants

Primary outcome timeframe

12 weeks

Results posted on

2018-09-18

Participant Flow

Participant milestones

Participant milestones
Measure	Amrubicin + Lenalidomide + Dexamethasone Amrubicin 40, 60, or 80 mg/m2 intravenous (IV) 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
Overall Study STARTED	14
Overall Study COMPLETED	14
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Amrubicin + Lenalidomide + Dexamethasone n=14 Participants Amrubicin 40, 60, or 80 mg/m2 intravenous (IV) 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
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=93 Participants
Age, Categorical >=65 years	6 Participants n=93 Participants
Sex: Female, Male Female	5 Participants n=93 Participants
Sex: Female, Male Male	9 Participants n=93 Participants
Region of Enrollment United States	14 participants n=93 Participants

PRIMARY outcome

Timeframe: 12 weeks

Outcome measures

Outcome measures
Measure	Amrubicin + Lenalidomide + Dexamethasone n=13 Participants Amrubicin 40, 60, or 80 mg/m2 intravenous (IV) 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
Response Rates After Amrubicin + Lenalidomide + Dexamethasone, Per International Myeloma Working Group Uniform Response Criteria Complete Response (CR) rate	0 percentage of participants
Response Rates After Amrubicin + Lenalidomide + Dexamethasone, Per International Myeloma Working Group Uniform Response Criteria Very Good Partial Response (VGPR) Rate	7.6 percentage of participants
Response Rates After Amrubicin + Lenalidomide + Dexamethasone, Per International Myeloma Working Group Uniform Response Criteria Total CR + VGPR	7.6 percentage of participants
Response Rates After Amrubicin + Lenalidomide + Dexamethasone, Per International Myeloma Working Group Uniform Response Criteria Partial Response (PR) Rate	15.4 percentage of participants
Response Rates After Amrubicin + Lenalidomide + Dexamethasone, Per International Myeloma Working Group Uniform Response Criteria Overall Response Rate (ORR = CR + VGPR + PR)	23 percentage of participants

SECONDARY outcome

Timeframe: 140 days

Outcome measures

Outcome measures
Measure	Amrubicin + Lenalidomide + Dexamethasone n=13 Participants Amrubicin 40, 60, or 80 mg/m2 intravenous (IV) 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
Duration of Response (DOR)	133 days Interval 129.0 to 140.0

SECONDARY outcome

Timeframe: 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)

Outcome measures

Outcome measures
Measure	Amrubicin + Lenalidomide + Dexamethasone n=13 Participants Amrubicin 40, 60, or 80 mg/m2 intravenous (IV) 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
Progression-free Survival (PFS)	96 days Interval 21.0 to 232.0

SECONDARY outcome

Timeframe: 9 months

Outcome measures

Outcome measures
Measure	Amrubicin + Lenalidomide + Dexamethasone n=13 Participants Amrubicin 40, 60, or 80 mg/m2 intravenous (IV) 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
Time-to-next Treatment	92 days Interval 24.0 to 281.0

Adverse Events

Amrubicin + Lenalidomide + Dexamethasone

Serious events: 3 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Amrubicin + Lenalidomide + Dexamethasone n=14 participants at risk Amrubicin 40, 60, or 80 mg/m2 intravenous (IV) 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
Infections and infestations Sepsis	7.1% 1/14 • Up to 12 weeks treatment, plus a minimum of 30 days follow-up
Nervous system disorders Cord compression	7.1% 1/14 • Up to 12 weeks treatment, plus a minimum of 30 days follow-up
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Progressive disease	7.1% 1/14 • Up to 12 weeks treatment, plus a minimum of 30 days follow-up

Other adverse events

Other adverse events
Measure	Amrubicin + Lenalidomide + Dexamethasone n=14 participants at risk Amrubicin 40, 60, or 80 mg/m2 intravenous (IV) 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
Blood and lymphatic system disorders Thrombocytopenia	78.6% 11/14 • Up to 12 weeks treatment, plus a minimum of 30 days follow-up
Blood and lymphatic system disorders Anemia	85.7% 12/14 • Up to 12 weeks treatment, plus a minimum of 30 days follow-up
Blood and lymphatic system disorders Neutropenia	64.3% 9/14 • Up to 12 weeks treatment, plus a minimum of 30 days follow-up
Vascular disorders Deep venous thrombosis	7.1% 1/14 • Up to 12 weeks treatment, plus a minimum of 30 days follow-up
Gastrointestinal disorders Nausea	35.7% 5/14 • Up to 12 weeks treatment, plus a minimum of 30 days follow-up
Gastrointestinal disorders Vomiting	14.3% 2/14 • Up to 12 weeks treatment, plus a minimum of 30 days follow-up
Gastrointestinal disorders Diarrhea	50.0% 7/14 • Up to 12 weeks treatment, plus a minimum of 30 days follow-up
Gastrointestinal disorders Anorexia	21.4% 3/14 • Up to 12 weeks treatment, plus a minimum of 30 days follow-up
Gastrointestinal disorders Constipation	14.3% 2/14 • Up to 12 weeks treatment, plus a minimum of 30 days follow-up
Gastrointestinal disorders Abdominal pain	14.3% 2/14 • Up to 12 weeks treatment, plus a minimum of 30 days follow-up
Investigations Elevated AST/ALT	35.7% 5/14 • Up to 12 weeks treatment, plus a minimum of 30 days follow-up
Investigations Hypoalbuminemia	42.9% 6/14 • Up to 12 weeks treatment, plus a minimum of 30 days follow-up
Infections and infestations Infection	78.6% 11/14 • Up to 12 weeks treatment, plus a minimum of 30 days follow-up
General disorders Insomnia	14.3% 2/14 • Up to 12 weeks treatment, plus a minimum of 30 days follow-up
General disorders Dysgeusia	14.3% 2/14 • Up to 12 weeks treatment, plus a minimum of 30 days follow-up
General disorders Headache	7.1% 1/14 • Up to 12 weeks treatment, plus a minimum of 30 days follow-up
Nervous system disorders Dizziness	21.4% 3/14 • Up to 12 weeks treatment, plus a minimum of 30 days follow-up
Musculoskeletal and connective tissue disorders Bone pain	35.7% 5/14 • Up to 12 weeks treatment, plus a minimum of 30 days follow-up
Musculoskeletal and connective tissue disorders Osteonecrosis	7.1% 1/14 • Up to 12 weeks treatment, plus a minimum of 30 days follow-up
Musculoskeletal and connective tissue disorders Muscle weakness	7.1% 1/14 • Up to 12 weeks treatment, plus a minimum of 30 days follow-up
Musculoskeletal and connective tissue disorders Muscle cramps	14.3% 2/14 • Up to 12 weeks treatment, plus a minimum of 30 days follow-up
Skin and subcutaneous tissue disorders Graft vs host diseae (GvHD)	7.1% 1/14 • Up to 12 weeks treatment, plus a minimum of 30 days follow-up
Skin and subcutaneous tissue disorders Skin disorder	21.4% 3/14 • Up to 12 weeks treatment, plus a minimum of 30 days follow-up
Skin and subcutaneous tissue disorders Alopecia	28.6% 4/14 • Up to 12 weeks treatment, plus a minimum of 30 days follow-up
Respiratory, thoracic and mediastinal disorders Dyspnea	7.1% 1/14 • Up to 12 weeks treatment, plus a minimum of 30 days follow-up
Respiratory, thoracic and mediastinal disorders Hiccups	14.3% 2/14 • Up to 12 weeks treatment, plus a minimum of 30 days follow-up
Investigations Creatinine	28.6% 4/14 • Up to 12 weeks treatment, plus a minimum of 30 days follow-up
Investigations Hypokalemia	35.7% 5/14 • Up to 12 weeks treatment, plus a minimum of 30 days follow-up
General disorders Fatigue	50.0% 7/14 • Up to 12 weeks treatment, plus a minimum of 30 days follow-up
Cardiac disorders Decreased ejection fraction (transient)	7.1% 1/14 • Up to 12 weeks treatment, plus a minimum of 30 days follow-up

Additional Information

Michaela Liedtke, MD

Stanford University

Phone: 650-498-6000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place