Clinical trial NCT01323751: Study of ACY-1215 Alone and in Combination With Bortezomib and Dexamethasone in Multiple Myeloma
Official title: A Phase 1/2, Open-Label, Multicenter Study of ACY-1215 Administered Orally as Monotherapy and in Combination With Bortezomib and Dexamethasone for the Treatment of Relapsed or Relapsed/Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Lead sponsor: Celgene
Sponsor class: INDUSTRY
Collaborators: name: The Leukemia and Lymphoma Society
First posted: 2011-03-28
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Phase 1(a \& b): To evaluate the side effects and determine the best dose of oral ACY-1215 as monotherapy, and also in combination with bortezomib and dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma.

Phase 2a: To determine the objective response rate of oral ACY-1215 in combination with bortezomib and dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma.


Eligibility criteria: Inclusion Criteria:

* Patient has relapsed or relapsed/refractory MM with measurable disease parameters according to the International Myeloma Working Group (IMWG) Criteria

  * Refractory is defined as experiencing less than minimal response (MR) to or progressive disease (PD) within 60 days after completion of the most recent anti-MM regimen
  * Relapsed is defined as experiencing PD that requires therapy but which is not refractory following the achievement of stable disease (SD) or better to the most recent anti-MM regimen.
* Patient received at least 2 prior regimens for MM.
* Patient received prior treatment for MM with a proteasome inhibitor and an immunomodulatory drug, unless not a candidate for a proteasome inhibitor or an immunomodulatory drug.
* Patient either is not a candidate for autologous stem cell transplant (ASCT), has declined the option of ASCT, or has relapsed after prior ASCT.
* Patient is ≥18 years of age.
* Patient has a Karnofsky Performance Status score of ≥70
* Patient has adequate bone marrow reserve, as evidenced by:

  * Absolute neutrophil count (ANC) of ≥1.0x109/L.
  * Platelet count of ≥ 75x109/L in patients in whom \<50% of bone marrow nucleated cells are plasma cells and ≥50x109/L in patients in whom more than 50% of bone marrow nucleated cells are plasma cells.
* Patient has adequate renal function (calculated creatinine clearance of ≥30 mL/min according to the Cockroft-Gault)
* Patient has adequate hepatic function (serum bilirubin values \<2.0 mg/dL and ALT and/or AST values \<3 × the upper limit of normal ULN).
* Patient has a corrected serum calcium ≤ULN.

Exclusion Criteria

* Patient has received any of the following therapies:

  * Radiotherapy or systemic therapy within 2 weeks of baseline
  * Prior peripheral autologous stem cell transplant within 12 wks of Baseline.
  * Prior allogeneic stem cell transplant.
  * Prior treatment with an HDAC inhibitor.
* Patient has an active systemic infection requiring treatment.
* Patient has a history of other malignancies unless has undergone definitive treatment more than 5 yrs prior to study and without evidence of recurrent malignant disease (excluding basal cell carcinoma of the skin; superficial carcinoma of the bladder; carcinoma of the prostate with a current prostate-specific antigen \<0.1 ng/mL; or cervical intraepithelial neoplasia).
* Patient has known or suspected HIV, positive for hepatitis B or is known or suspected to have active hepatitis C infection.
* Patient has a history of significant cardiovascular, neurological, endocrine, gastrointestinal, respiratory, or inflammatory illness including recent myocardial infarction (within 6 months)or stroke; hypertension requiring \>2 medications for adequate control; diabetes mellitus with \>2 episodes of ketoacidosis in the preceding 12 months; or chronic obstructive pulmonary disease (COPD) requiring \>2 hospitalizations in the preceding 12 months.
* Patient has a QTcF value of \>480 msec; family or personal history of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy; previous history of drug-induced QTc prolongation
* Patient has \> Grade 2 painful neuropathy or peripheral neuropathy
* Patient has a history of allergic reaction attributable to bortezomib or other compounds containing boron or mannitol (Phase 1b and 2a only)

Primary outcomes:
measure: Phase 1 (a & b): To determine the maximum tolerated dose of ACY-1215 as monotherapy or in combination with bortezomib and dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma.
timeFrame: Upon completion of 21-day treatment cycle
measure: Phase 2a: To determine the objective response rate to ACY-1215 in combination with bortezomib and dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma.
timeFrame: Assessed every other treatment cycle (cycles 2, 4 and 6)
Secondary outcomes:
measure: Characterize the safety of ACY-1215 alone or in combination with bortezomib and dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma
timeFrame: Up to 24 weeks
measure: Determine the single- and multiple-dose PK of ACY-1215 alone and in combination with bortezomib and dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma
timeFrame: Upon completion of 21 day treatment cycle
measure: Evaluate the pharmacodynamics of ACY-1215 alone or in combination with bortezomib and dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma.
timeFrame: Up to 24 weeks.
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Winship Cancer Institute, Emory University
state: Georgia
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: New York
country: United States
facility: Mt. Sinai Medical Center
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin - Clinical Cancer Center
state: Wisconsin
Study officials:
affiliation: Winship Cancer Institute, Emory University
name: Sagar Lonial, MD
role: PRINCIPAL_INVESTIGATOR
References: