Study of ACY-241 Alone and in Combination With Pomalidomide and Dexamethasone in Multiple Myeloma
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| ClinicalTrials.gov Identifier: NCT02400242 |
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Recruitment Status :
Active, not recruiting
First Posted : March 27, 2015
Last Update Posted : April 9, 2020
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Sponsor:
Celgene
Information provided by (Responsible Party):
Celgene
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Brief 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).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Multiple Myeloma | Drug: ACY-241 Drug: Pomalidomide Drug: Dexamethasone | Phase 1 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 85 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | May 7, 2015 |
| Estimated Primary Completion Date : | October 29, 2020 |
| Estimated Study Completion Date : | January 27, 2021 |
Resource links provided by the National Library of Medicine
Genetics Home Reference related topics:
Multiple myeloma
MedlinePlus related topics:
Multiple Myeloma
| Arm | Intervention/treatment |
|---|---|
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Experimental: ACY-241, Pomalidomide, and dexamethasone
Open label dosing cohorts will evaluate oral ACY-241 (dosing ranging from 180 mg to 480 mg days 1-21) in combination with oral pomalidomide (4 mg days 1-21), and oral dexamethasone (40 mg qd on days 1, 8, 15, 22).
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Drug: ACY-241
Dose escalation up to 480 mg administered orally on Days 1-21 of a 28 day cycle.
Other Name: Histone deacetylase inhibitor Drug: Pomalidomide 4 mg qd dosed on days 1-21 of a 28 day cycle
Other Name: immunomodulatory agent Drug: Dexamethasone 40 mg qd on days 1, 8, 15, 22
Other Name: corticosteriod |
Primary Outcome Measures :
- Maximum tolerated dose of ACY-241 as monotherapy as assessed by dose limiting toxicities [ Time Frame: Cycle 1 (28 days) ]
- Maximum tolerated dose of ACY-241 in combination with pomalidomide and low dose dexamethasone as assessed by dose limiting toxicities [ Time Frame: Cycle 2 (28 days) ]First cycle of combination therapy
Secondary Outcome Measures :
- Frequency and severity of AEs as measured by safety and tolerability [ Time Frame: Cycle 1 (28 days) ]
- Single- and multiple-dose peak-plasma concentration [ Time Frame: Cycle 1 days 1, 2, 15 and 16 ]
- Single- and multiple-dose area under the plasma concentration versus time curve [ Time Frame: Cycle 1 days 1, 2, 15 and 16 ]
- Change in acetylation of histone and tubulin as a measure of pharmacodynamics [ Time Frame: Cycles 1 days 1, 2, 15, 16 and 22 ]
- Change in fetal hemoglobin expression as a measure of pharmacodynamics [ Time Frame: Cycles 1 days 1, 2, 15, 16 and 22 ]
- ACY-241 metabolite concentration in blood samples [ Time Frame: Cycles 1 days 1, 2, 15, 16 and 22 ]
- Exposure response analyses of potential biomarkers of response. [ Time Frame: Cycles 1 days 1, 2, 15, 16 and 22 ]
- Frequency and severity of AEs as measured by safety and tolerability in combination [ Time Frame: Beginning at Cycle 2 (28 day cycle each) until end of treatment ]
- Change in fetal hemoglobin expression as a measure of pharmacodynamics [ Time Frame: Cycle 2 days 1, 2, 15, 16 and 22 ]
- Change in acetylation of histone and tubulin as a measure of pharmacodynamics [ Time Frame: Cycle 2 days 1, 2, 15, 16 and 22 ]
- Single- and multiple-dose area under the plasma concentration versus time curve [ Time Frame: Cycle 2 days 1, 2, 15, and 16 ]
- Quantification of M-protein as a measure of anti-tumor activity [ Time Frame: Day 1 of each cycle beginning at Cycle 2 ]
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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
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): NCT02400242
Locations
Show 17 study locations
Sponsors and Collaborators
Celgene
Investigators
| Principal Investigator: | Ruben Niesvizky, MD | Weill Medical College of Cornell University |
| Responsible Party: | Celgene |
| ClinicalTrials.gov Identifier: | NCT02400242 |
| Other Study ID Numbers: |
ACE-MM-200 |
| First Posted: | March 27, 2015 Key Record Dates |
| Last Update Posted: | April 9, 2020 |
| Last Verified: | April 2020 |
Additional relevant MeSH terms:
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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 |
Pomalidomide Histone Deacetylase Inhibitors Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Antineoplastic Agents, Hormonal Antineoplastic Agents Immunologic Factors Angiogenesis Inhibitors |