ACY-1215 for Relapsed/Refractory Lymphoid Malignancies

NCT02091063 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: AAAM4054
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 2

Brief Summary

This will be an open-label, single agent, multi-institutional phase Ib/II study of ACY-1215 for the treatment of patients with relapsed or refractory lymphoid malignancies. The target population will include patients with histologically confirmed relapsed or refractory non-Hodgkin's lymphoma or Hodgkin's lymphoma, with an expansion cohort of patients with mantle cell lymphoma. The phase Ib will be conducted to determine the safety and tolerability of two dosing schedules of ACY-1215 monotherapy in patients with lymphoid malignancies. Patients will be accrued simultaneously to two dose cohorts (Arm A and Arm B) of ACY-1215. Selection into each cohort will occur by alternation. All patients will take the prescribed dose of ACY-1215 orally for 28 consecutive days. Patients enrolled into Arm A will take ACY-1215 160 mg daily (QD), whereas patients enrolled into Arm B will take ACY-1215 160 mg twice daily (BID). ACY-1215 will be supplied as a liquid for oral administration (PO). Each dose will be administered at least 1 hour after ingestion of food followed by at least 4 ounces of water. Patients will be instructed not to ingest food or other oral medication for at least 2 hours after each ACY-1215 dose. Frequency in phase II will be determined based on Phase Ib results.

Conditions

Lymphoma; Lymphoid Malignancies

Keywords

hematologic malignancies; hodgkin; hodgkins; non-hodgkin; non-hodgkins; mantle cell lymphoma; follicular; lymphoma; lymphoid malignancies

Outcome Measures

Primary Outcomes (2)

• Number of Patients Who Experience a Dose-limiting Toxicity (DLT)

  This is designed to establish the safety of 2 dose schedules of ACY-1215 in patients with relapsed or refractory lymphoid malignancies treated with ACY-1215. If more than 1/3 or 2/6 patients experience a DLT in Phase I, there will be no expansion.

  Up to 1 year

• Objective Response Rate

  The anti-tumor activity of ACY-1215 will be measured by the number of subjects with the response rate in Phase II: complete response \[CR\] and partial response \[PR\]. Complete Response (CR) - Disappearance of all non-target lesions by PET/CT. Nodal Mass: (a) FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative or (b) Variably FDG-avid or PET negative; regression to normal size on CT. Spleen/Liver: Not palpable, nodules disappeared. Partial Response (PR) - Regression of measurable disease and no new sites. Nodal Mass: 50% decrease in SPD of up to 6 largest dominant masses; no increase in size of other nodes, (a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site; (b) Variably FDG-avid or PET negative; regression on CT. Spleen/Liver: 50% decrease in SPD of nodules.

  Up to 3 years

Study Arms (1)

Phase Ib and II: ACY-1215

EXPERIMENTAL

Participants will receive Phase Ib Arm A: ACY-1215 QD or Arm B: ACY-1215 BID. Once Phase I dosing schedule has been determined. 160 mg BID dosing will be administered for Phase II.

Drug: ACY-1215

Interventions

ACY-1215 DRUG

All patients will take the oral ACY-1215 160mg for 28 consecutive days on a 28-day treatment cycle. Each dose will be administered at least 1 hour after ingestion of food and followed by at least 4 ounces of water. Patients will be instructed not to ingest food or other oral medication for at least 2 hours after each ACY-1215 dose.

Also known as: Ricolinostat

Phase Ib and II: ACY-1215

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed relapsed or refractory non-Hodgkin's lymphoma or Hodgkin's lymphoma (World Health Organization criteria), for which they are unwilling or unable to undergo an autologous stem cell transplant. Patients may have relapsed after prior stem cell transplant.
• Must have received first line chemotherapy. No upper limit to number of prior therapies.
• Patients must have measurable disease.
• Patients must be age ≥ 18.
• Patient has a Karnofsky Performance Status score of ≥70 or Eastern Cooperative Oncology Group (ECOG) performance status score of ≤2
• The patient or the patient's legal representative is able to understand the risks of the study and provide signed informed consent and authorization to use protected health information (in accordance with national and local privacy regulations).
• Patient has adequate bone marrow reserve, as evidenced by:
• Absolute neutrophil count (ANC) of ≥1.0x109/L.
• Platelet count of ≥50x109/L.
• Patient has adequate renal function, as evidenced by a creatinine within the institutional limits of normal or a calculated creatinine clearance of ≥30 mL/min according to the Cockcroft-Gault equation.
• Patient has adequate hepatic function, as evidenced by serum bilirubin values \<2.0 mg/dL and serum alanine transaminase (ALT) and/or aspartate transaminase (AST) values \<3 × the upper limit of normal (ULN) of the local laboratory reference range. (Patients with isolated elevations in alkaline phosphatase (ALP) \<5 × ULN in the presence of bony disease are not excluded from participating in the study.)
• Females of childbearing potential must have a negative urine or serum pregnancy test within 7 days of (C1D1) and have adequate contraception. (A female is considered to be not of childbearing potential if she has undergone bilateral oophorectomy or if she has been menopausal without a menstrual period for 12 consecutive months.)

You may not qualify if:

• Prior Therapy
• Patients who have had chemotherapy or radiotherapy within 2 weeks of study drug treatment or those who have not recovered from adverse events due to agents administered
• Systemic steroids that have not been stabilized to the equivalent of ≤10 mg/day prednisone during the 7 days prior to the start of the study drugs.
• No monoclonal antibody within 3 months unless evidence of disease progression.
• Patients may not be receiving any other investigational agents.
• Patients with known central nervous system metastases, including lymphomatous meningitis
• Any known cardiac abnormalities such as:
• Congenital long QT syndrome
• Corrected QT (QTc) interval ≥ 500 milliseconds;
• Uncontrolled inter-current illness
• Pregnant or nursing women
• Patient is known to be Human Immunodeficiency Virus (HIV)-positive
• Active Hepatitis A, Hepatitis B, or Hepatitis C infection
• Patient has a history of surgery that would interfere with the administration or absorption of the oral study drugs

Sponsors & Collaborators

• Jennifer Amengual: lead
• Acetylon Pharmaceuticals Incorporated: collaborator

Study Sites (2)

Moffit Cancer Center

Tampa, Florida, 33612, United States

Location

Columbia University Medical Center

New York, New York, 10019, United States

Location

MeSH Terms

Conditions

Lymphoma; Hematologic Neoplasms; Lymphoma, Mantle-Cell

Interventions

ricolinostat

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms by Site; Hematologic Diseases; Lymphoma, Non-Hodgkin

Results Point of Contact

• Title: Jennifer Amengual, MD
• Organization: Columbia University

jea2149@cumc.columbia.edu

212-305-0591

Study Officials

• Jennifer E Amengual, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: March 14, 2014
• First Posted: March 19, 2014
• Study Start: April 2, 2014
• Primary Completion: February 25, 2019
• Study Completion: May 5, 2019
• Last Updated: August 6, 2024
• Results First Posted: August 6, 2024

Record last verified: 2024-07

Locations

US (2)