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ACY-1215 in Combination With BCR Pathway Inhibitors in Relapsed CLL | Clinical Trials | Clareo Health

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ACY-1215 in Combination With BCR Pathway Inhibitors in Relapsed CLL

A Phase Ib Study of ACY-1215 in Combination With BCR Pathway Inhibitors in Relapsed Chronic Lymphocytic Leukemia

NCT02787369•Dana-Farber Cancer Institute

Summary

This research study is studying a drug called ACY-1215 in combination with ibrutinib or idelalisib as a possible treatment for Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL).

Detailed Description

This research study is a Phase I clinical trial. The investigators are studying the combination of the B-cell receptor (BCR) pathway inhibitors with ricolinostat, in order to try to enhance both the initial remission and to help improve the response in those who relapse after a first inhibitor and are receiving a second. The FDA (the U.S. Food and Drug Administration) has not approved ACY-1215 as a treatment for any disease. ACY-1215 or ricolinostat is a histone deacetylase inhibitor, specifically HDAC6. The FDA has approved idelalisib as well as ibrutinib as treatment options for Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL).

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Participants must have confirmed CLL/SLL relapsed after at least one prior therapy and currently in need of treatment by IWCLL 2008 criteria
•Age ≥ 18
•ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
•For the ibrutinib arm only: participants must not currently require ongoing anticoagulation for any reason, or have had any major bleeding events within 6 months of enrollment
•Participants must have normal organ and marrow function as defined below:
•* Absolute neutrophil count (ANC) \> 1000 K/μL and platelet count \> 30,000 K/μL independent of transfusion support.
•* total bilirubin \< 2X institutional upper limit of normal (ULN) unless predominantly indirect and therefore likely due to hemolysis or Gilbert's syndrome
•* AST(SGOT)/ALT(SGPT) ≤3X institutional upper limit of normal for ibrutinib arm; within normal limits on the idelalisib arm
•* creatinine \< 2X ULN
•Participants must have measurable disease, including at least one of the following: an absolute B cell count \> 5000/uL, OR lymphadenopathy with at least one lymph node \> 2 cm in long axis, OR palpable splenomegaly, OR cytopenias (Hb \< 11 g/dL or platelets \< 100K) together with bone marrow infiltration
+2 more criteria

Exclusion Criteria

•Participants who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier.
•Participants who are receiving any other investigational agents.
•Prior therapy with an HDAC inhibitor.
•Participants with a history of poor tolerance to either ibrutinib or idelalisib should not be enrolled on the arm containing that drug, but may be enrolled to the other arm. Must agree not to share study medication with another person.
•Participants requiring any medications or substances that are strong inducers or inhibitors of CYP3A4 are ineligible. Those who may discontinue these medications are eligible after a 7 day washout period. . Mild or moderate inducers or inhibitors of CYP3A4 are permitted but moderate inhibitors will require dose reduction of ibrutinib (see section 5.5).
•Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
•Pregnant women are excluded from this study because ACY-1215, as well as both ibrutinib and idelalisib, have unknown effects on a developing fetus or newborn. Breastfeeding should be discontinued if the mother is treated on this research protocol.
•HIV-positive participants on CYP3A4 modulating antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with ACY-1215, ibrutinib or idelalisib. In addition, these participants are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
•Participants who require active chemotherapy for another cancer. Those requiring hormonal therapy or radiation therapy may be considered for enrollment on a case by case basis.
•Corrected QT interval using Fridericia's formula (QTcF) value \> 480 msec at screening; family or personal history of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy at screening; previous history of drug-induced QTc prolongation or the need for treatment with medications known or suspected of producing prolonged QTc intervals on ECG.
+4 more criteria

Locations (1)

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Key Dates

Start Date

May 1, 2016

Primary Completion Date

April 1, 2026

Completion Date

April 1, 2027

Last Updated

January 7, 2026

Enrollment

ACTUAL participants

Conditions

Recurrent Chronic Lymphoid Leukemia

Interventions

ACY-1215

DRUG

Ibrutinib

DRUG

Idelalisib

DRUG