Study of ACY-241 Alone and in Combination With Pomalidomide and Dexamethasone in Multiple Myeloma

Multiple Myeloma Clinical Trial

Official title:

A Phase 1a/1b Multicenter, Single-Arm, Open-Label, Dose-Escalation Study to Determine the Maximum Tolerated Dose, Safety, and Preliminary Activity of Oral ACY-241 Alone and in Combination With Pomalidomide and Low-Dose Dexamethasone in Patients With Relapsed or Relapsed-and-Refractory Multiple Myeloma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02400242
• Other study ID #: ACE-MM-200
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: May 7, 2015
• Est. completion date: January 31, 2024

Study information

• Verified date: October 2023
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phase 1a/1b, multicenter, single-arm, open-label, dose escalation study to determine the maximum tolerated dose (MTD) and evaluate the safety and preliminary antitumor activity of ACY-241 for oral administration as monotherapy and in combination therapy with orally administered pomalidomide and low-dose dexamethasone in eligible patients with relapsed or relapsed-and-refractory multiple myeloma (MM).

Description:

During phase 1a, patients will receive 1 cycle of ACY-241 monotherapy. Patients who complete the ACY-241 monotherapy cycle without a dose limiting toxicity (DLT) and are clinically stable may continue to phase 1b combination therapy, beginning with Cycle 2. During phase 1b, patients will receive ACY 241 in combination with pomalidomide and low dose dexamethasone at the currently approved pomalidomide dose and schedule. Each cohort of patients in phase 1a and phase 1b will consist of at least 3 patients. The first patient enrolled in each cohort of phase 1a will be observed for 1 week before enrollment of subsequent patients in the cohort. Patients who withdraw consent before entering phase 1b will be replaced. (Replacement patients must complete phase 1a prior to continuing to phase 1b.) Patients who experience a DLT or other unacceptable toxicity in Cycle 1 of phase 1a monotherapy or Cycle 2, the first cycle of phase 1b combination therapy, will be removed from study treatment. An assessment of the safety of treatment will be completed by the Safety Review Committee (SRC) prior to dose-escalation.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 85
• Est. completion date: January 31, 2024
• Est. primary completion date: January 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Must have a documented diagnosis of MM and have relapsed or relapsed-and-refractory disease. All patients must have relapsed after having achieved at least stable disease (SD) for at least 1 cycle of treatment to at least 1 prior regimen and then developed progressive disease (PD). Relapsed-and-refractory patients also have documented evidence of PD during or within 60 days of completing last treatment

• Must have undergone prior treatment with at least 2 cycles of lenalidomide and at least 2 cycles of proteasome inhibitor unless not a candidate.

• May have undergone prior treatment with pomalidomide if patient is not refractory to pomalidomide and has previously achieved a response of MR or better to pomalidomide.

• Must have measurable disease (serum M-protein or urine M-protein).

• Must have Eastern Cooperative Oncology Group (ECOG) Performance score of 0, 1, or 2.

• Must be able to take low-dose aspirin, low molecular weight heparin, or other equivalent antithrombotic or anticoagulant daily as prophylactic anticoagulation.

Key Exclusion Criteria:

• Prior therapy with pomalidomide with best response of PD or SD.

• Prior therapy with histone deacetylase (HDAC) inhibitor.

• Any of the following laboratory abnormalities: Absolute neutrophil count(ANC) < 1,000/µL, Platelet count < 75,000/µL or < 50,000/µL for patients in whom = 50% of bone marrow nucleated cells are plasma cells, Hemoglobin < 8 g/dL, Creatinine clearance < 45 mL/min according to Cockcroft-Gault formula. If creatinine clearance calculated from the 24 hour urine sample is = 45 mL/min, patient will qualify for the trial, Aspartate transaminase (AST) or Alanine transaminase (ALT) > 3.0 × Upper Limited Normal (ULN), Serum total bilirubin > 2.0 mg/dL or > 3.0 × ULN for patients with hereditary benign hyperbilirubinaemia.

• Hematologic growth factors are not allowed at screening or during the first cycle of phase 1a or 1b.

• Nonsecretory myeloma or free light chain detected in serum only (ogliosecretory).

• Hypersensitivity to thalidomide, lenalidomide, pomalidomide, or dexamethasone

• Patients who received an allogeneic bone marrow or allogeneic peripheral blood stem cell transplant less than 12 months prior to initiation of study

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• ACY-241
Dose escalation up to 480 mg administered orally on Days 1-21 of a 28 day cycle.
• Pomalidomide
4 mg qd dosed on days 1-21 of a 28 day cycle
• Dexamethasone
40 mg qd on days 1, 8, 15, 22

Locations

Country	Name	City	State
France	Local Institution - 340	Lille
France	Local Institution - 341	Nantes Cedex 01
Germany	Local Institution - 330	Heidelberg
Greece	Local Institution - 320	Athens
Spain	Local Institution - 301	Pamplona
Spain	Local Institution - 300	Salamanca
United States	Local Institution - 103	Atlanta	Georgia
United States	Local Institution - 104	Boston	Massachusetts
United States	Local Institution - 105	Boston	Massachusetts
United States	Gabrail Cancer Center Research	Canton	Ohio
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	University of Miami Medical Center	Miami	Florida
United States	Local Institution - 101	New York	New York
United States	CTRC at The UT Health Science Center at San Antonio	San Antonio	Texas
United States	Local Institution - 111	Seattle	Washington
United States	Local Institution - 108	Tampa	Florida
United States	Local Institution - 109	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  France,  Germany,  Greece,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose of ACY-241 as monotherapy as assessed by dose limiting toxicities		Cycle 1 (28 days)
Primary	Maximum tolerated dose of ACY-241 in combination with pomalidomide and low dose dexamethasone as assessed by dose limiting toxicities	First cycle of combination therapy	Cycle 2 (28 days)
Secondary	Frequency and severity of AEs as measured by safety and tolerability		Cycle 1 (28 days)
Secondary	Single- and multiple-dose peak-plasma concentration		Cycle 1 days 1, 2, 15 and 16
Secondary	Single- and multiple-dose area under the plasma concentration versus time curve		Cycle 1 days 1, 2, 15 and 16
Secondary	Change in acetylation of histone and tubulin as a measure of pharmacodynamics		Cycles 1 days 1, 2, 15, 16 and 22
Secondary	Change in fetal hemoglobin expression as a measure of pharmacodynamics		Cycles 1 days 1, 2, 15, 16 and 22
Secondary	ACY-241 metabolite concentration in blood samples		Cycles 1 days 1, 2, 15, 16 and 22
Secondary	Exposure response analyses of potential biomarkers of response.		Cycles 1 days 1, 2, 15, 16 and 22
Secondary	Frequency and severity of AEs as measured by safety and tolerability in combination		Beginning at Cycle 2 (28 day cycle each) until end of treatment
Secondary	Change in fetal hemoglobin expression as a measure of pharmacodynamics		Cycle 2 days 1, 2, 15, 16 and 22
Secondary	Change in acetylation of histone and tubulin as a measure of pharmacodynamics		Cycle 2 days 1, 2, 15, 16 and 22
Secondary	Single- and multiple-dose area under the plasma concentration versus time curve		Cycle 2 days 1, 2, 15, and 16
Secondary	Quantification of M-protein as a measure of anti-tumor activity		Day 1 of each cycle beginning at Cycle 2

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting