Brief Summary

RATIONALE: AR-42 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase I trial is studying the side effects and best dose of AR-42 in treating patients with advanced or relapsed multiple myeloma, chronic lymphocytic leukemia, or lymphoma.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at P50-P75 for phase_1

Timeline

Completed

Started May 2010

Longer than P75 for phase_1

Geographic Reach

1 country

1 active site

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

6.7 years study duration

Study Start

First participant enrolled

May 4, 2010

Completed

13 days until next milestone

First Submitted

Initial submission to the registry

May 17, 2010

Completed

7 days until next milestone

First Posted

Study publicly available on registry

May 24, 2010

Completed

6.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 7, 2017

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 7, 2017

Completed

Last Updated

June 4, 2018

Status Verified

May 1, 2018

Enrollment Period

6.7 years

First QC Date

May 17, 2010

Last Update Submit

May 31, 2018

Conditions

Outcome Measures

Primary Outcomes (1)

Adverse events described using the NCI CTCAE criteria
Up to 3 years

Secondary Outcomes (3)

Clinical benefit
Up to 3 years
Duration of response
Up to 3 years
Time to progression
Up to 3 years

Study Arms (2)

Arm I (Hematologic Malignancies)

EXPERIMENTAL

Patients will receive orally administered AR-42 three times per week (Mon, Wed, and Fri preferred) in cycles of 28 days (3 weeks of 3-times-per-week dosing followed by a 7-day off-treatment period).

Other: Pharmacodynamic StudiesOther: Fatigue InventoryOther: Pharmacogenomic studiesDrug: AR-42

Arm II (Solid Tumors)

EXPERIMENTAL

Patients will receive orally administered AR-42 three times per week (Mon, Wed, and Fri preferred) in cycles of 28 days (3 weeks of 3-times-per-week dosing followed by a 7-day off-treatment period).

Drug: AR-42

Interventions

Pharmacodynamic StudiesOTHER

Assess at baseline (pre-dose day 1 of cycle 1), approximately 24 hours after the first dose, pre-dose days 2 and 3, and pre-dose day 19 for histone acetylation of tumor cells (CLL patients) or mononuclear cells (PBMCs for lymphoma, myeloma, and solid tumor patients). Cytokine studies will be collected pre-dose on days 1, 2, 8, 15, 19 of cycle 1, day 1 of cycle 2, and pre-dose days 1, 8, 15 of cycle 3.

Also known as: correlative studies

Arm I (Hematologic Malignancies)

Fatigue InventoryOTHER

Brief Fatigue Inventory should take each patient approximately 5 minutes to fill out this survey per instance on day 1 of every cycle.

Also known as: quality-of-life assessmentBrief

Arm I (Hematologic Malignancies)

Pharmacogenomic studiesOTHER

Baseline germ line DNA from buccal swabs will be collected for analysis of drug (AR-42) metabolism SNPs and other biologic SNPs that might predict immune or disease response to therapy. Pharmacogenetic status of key metabolizing enzymes (eg, CYP3A5, UGT1A8) and transporter proteins (SLCO1B1, ABCG2) will also be considered for their role in drug clearance in individual patients.

Arm I (Hematologic Malignancies)

AR-42DRUG

Administered orally three times per week (Mon, Wed, and Fri preferred) in cycles of 28 days (3 weeks of 3-times-per-week dosing followed by a 7-day off-treatment period).

Arm I (Hematologic Malignancies)Arm II (Solid Tumors)

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

Inclusion Hematologic Malignances Arm * Patients must have CLL, prolymphocytic leukemia, or lymphoma (Hodgkins or Non-Hodgkins) as defined by 2008 WHO criteria or multiple myeloma as defined by IMWG criteria * Patients must have received at least one prior antineoplastic therapy, must have progressed after at least 1 prior therapy, and for whom no standard therapy is available or whom decline such options; prior autologous and/or allogeneic transplant is permitted * Prior biologic therapy or prior radiation is permitted; however, at least 28 days must have elapsed since the completion of prior therapy and patients must have recovered from all therapy-associated toxicities to no greater than grade 1 at the time of registration * Patients with symptomatic disease may receive palliative corticosteroids up to 1 week before initiating therapy * Patients must be off any prior chemotherapy for at least 28 days or 3 half lives, whichever is longer, and all therapy-related toxicity must have resolved to grade 1 or less * ANC \>= 1000/uL * Total bilirubin \< 1.5 mg/dL * Serum creatinine =\< 1.5x institutional upper limit of normal or estimated creatinine clearance \>= 50 ml/min by MDRD (original or abbreviated), or measured creatinine clearance \>= 50 mL/min * ECOG/WHO performance score of 0-1 * Patients must be able to swallow capsules * Patients or their legal representatives must be able to read, understand and provide informed consent to participate in the trial * Women with potential for child bearing must have a negative pregnancy test at screening; both men and women are required to use appropriate contraception during study * Platelet count \>= 50,000/uL * AST and ALT =\< 5x the institutional upper limit of normal Inclusion Solid Tumors Arm * Histologically or cytologically confirmed advanced or recurrent solid tumor malignancy. * Chemotherapy: up to three prior cytotoxic chemotherapy treatments. * Radiation Therapy: prior radiation therapy allowed. * Surgery: Prior curative and palliative intent surgery is allowed. * Age ≥ 18 years * ECOG performance status 0-1 * Life expectancy of greater than 12 weeks. * Patients must have normal organ and marrow function as defined below: * Leukocytes ≥ 3,000/mcL * Absolute neutrophil count ≥ 1,500/mcL * Platelets ≥ 100,000/mcL * Total bilirubin \< 1.5 mg/dL * AST(SGOT)/ALT(SGPT) ≤ 2.5 x institutional upper limit of normal (ULN); ≤ 5 x ULN in presence of liver metastasis * Creatinine ≤ 1.5 x ULN OR Creatinine clearance ≥ 50 mL/min by MDRD (original or abbreviated), or measured creatinine clearance ≥ 50 ml/min * Patients or their legal representatives must be able to read, understand and provide informed consent to participate in the trial * Women with potential for child bearing must have a negative pregnancy test at screening; both men and women are required to use appropriate contraception during study Exclusion Hematologic Malignances Arm * Pregnant women are excluded from this study * Patients with malabsorption or any other condition that in the opinion of the principal investigator could cause difficulty in absorption of drug * Breastfeeding should be discontinued if the mother is treated with AR-42 * Patients with malignant cells in the cerebrospinal fluid or parenchyma within the preceding 3 months or patients with primary CNS lymphoma are not eligible * Patients with uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP) are not eligible * Patients receiving concurrent corticosteroids less than 1 week prior to protocol therapy other than for physiologic maintenance treatment or control of AIHA or ITP * Concurrent use of complementary or alternative medicines that in the opinion of the principal investigator would confound the interpretation of toxicities and/or antitumor activity of the study drug * Patients with a "currently active" second malignancy that, in the opinion of the principal investigator, will interfere with patient participation, increase patient risk, shorten survival to \< 1 year, or confound data interpretation * Patients with a mean QTcB \> 450 msec in males and \> 470 msec in females * Patients who are receiving concurrent antineoplastic therapy * Any other medical condition, including mental illness or substance abuse, deemed by the principal investigator to likely interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results * Patients with significant cardiovascular disease, including a myocardial infarction or unstable angina within 6 months or unstable cardiac arrhythmias are not eligible for the study * Known HIV infection Exclusion Solid Tumors Arm * Pregnant women are excluded from this study * Patients with malabsorption or any other condition that in the opinion of the principal investigator could cause difficulty in absorption of drug * Patients with malignant cells in the cerebrospinal fluid or parenchyma within the preceding 3 months or patients with primary CNS lymphoma are not eligible * Patients with uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP) are not eligible * Patients receiving concurrent corticosteroids less than 1 week prior to protocol therapy other than for physiologic maintenance treatment or control of AIHA or ITP * Concurrent use of complementary or alternative medicines that in the opinion of the principal investigator would confound the interpretation of toxicities and/or antitumor activity of the study drug * Concurrent use of complementary or alternative medicines that in the opinion of the principal investigator would confound the interpretation of toxicities and/or antitumor activity of the study drug * Patients with a "currently active" second malignancy that, in the opinion of the principal investigator, will interfere with patient participation, increase patient risk, shorten survival to \< 1 year, or confound data interpretation. * Patients with a mean QTcB \> 450 msec in males and \> 470 msec in females * Patients who are receiving concurrent antineoplastic therapy. * Any other medical condition, including mental illness or substance abuse, deemed by the principal investigator to likely interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results. * Patients with significant cardiovascular disease, including a myocardial infarction or unstable angina within 6 months or unstable cardiac arrhythmias are not eligible for the study.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

Amir Mortazavilead
National Cancer Institute (NCI)collaborator
Arno Therapeuticscollaborator

Study Sites (1)

The Ohio State University James Cancer Hospital

Columbus, Ohio, 43210, United States

Location

Related Publications (3)

Collier KA, Valencia H, Newton H, Hade EM, Sborov DW, Cavaliere R, Poi M, Phelps MA, Liva SG, Coss CC, Wang J, Khountham S, Monk P, Shapiro CL, Piekarz R, Hofmeister CC, Welling DB, Mortazavi A. A phase 1 trial of the histone deacetylase inhibitor AR-42 in patients with neurofibromatosis type 2-associated tumors and advanced solid malignancies. Cancer Chemother Pharmacol. 2021 May;87(5):599-611. doi: 10.1007/s00280-020-04229-3. Epub 2021 Jan 25.
PMID: 33492438DERIVED
Sborov DW, Canella A, Hade EM, Mo X, Khountham S, Wang J, Ni W, Poi M, Coss C, Liu Z, Phelps MA, Mortazavi A, Andritsos L, Baiocchi RA, Christian BA, Benson DM, Flynn J, Porcu P, Byrd JC, Pichiorri F, Hofmeister CC. A phase 1 trial of the HDAC inhibitor AR-42 in patients with multiple myeloma and T- and B-cell lymphomas. Leuk Lymphoma. 2017 Oct;58(10):2310-2318. doi: 10.1080/10428194.2017.1298751. Epub 2017 Mar 7.
PMID: 28270022DERIVED
Cheng H, Xie Z, Jones WP, Wei XT, Liu Z, Wang D, Kulp SK, Wang J, Coss CC, Chen CS, Marcucci G, Garzon R, Covey JM, Phelps MA, Chan KK. Preclinical Pharmacokinetics Study of R- and S-Enantiomers of the Histone Deacetylase Inhibitor, AR-42 (NSC 731438), in Rodents. AAPS J. 2016 May;18(3):737-45. doi: 10.1208/s12248-016-9876-3. Epub 2016 Mar 4.
PMID: 26943915DERIVED

MeSH Terms

Conditions

Lymphoma, Extranodal NK-T-CellLymphoma, Large-Cell, AnaplasticImmunoblastic LymphadenopathyIntraocular LymphomaLymphoma, B-Cell, Marginal ZoneLymphoma, T-Cell, PeripheralLeukemia, ProlymphocyticBurkitt LymphomaLymphoma, Large B-Cell, DiffuseLymphoma, Non-HodgkinHodgkin DiseaseLymphoma, Large-Cell, ImmunoblasticPrecursor Cell Lymphoblastic Leukemia-LymphomaPrecursor T-Cell Lymphoblastic Leukemia-LymphomaLymphoma, T-Cell, CutaneousLymphoma, FollicularLymphoma, Mantle-CellMycosis FungoidesSezary SyndromeLeukemia, Lymphocytic, Chronic, B-CellMultiple MyelomaWaldenstrom Macroglobulinemia

Interventions

Pharmacogenomic Testing

Condition Hierarchy (Ancestors)

Lymphoma, T-CellLymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLymphadenopathyEye NeoplasmsNeoplasms by SiteLymphoma, B-CellLeukemia, LymphoidLeukemiaHematologic DiseasesEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsLeukemia, B-CellChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsNeoplasms, Plasma CellHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Genetic TestingClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisInvestigative TechniquesGenetic TechniquesGenetic ServicesHealth ServicesHealth Care Facilities Workforce and ServicesDiagnostic ServicesPreventive Health Services

Study Officials

Amir Mortazavi, MD
The Ohio State University James Cancer Hospital
PRINCIPAL INVESTIGATOR

Study Design

Study Type: interventional
Phase: phase 1
Allocation: NON RANDOMIZED
Masking: NONE
Purpose: TREATMENT
Intervention Model: SINGLE GROUP
Sponsor Type: OTHER
Responsible Party: SPONSOR INVESTIGATOR
PI Title: Principal Investigator

Study Record Dates

First Submitted

May 17, 2010

First Posted

May 24, 2010

Study Start

May 4, 2010

Primary Completion

January 7, 2017

Study Completion

January 7, 2017

Last Updated

June 4, 2018

Record last verified: 2018-05

Locations

US(1)

AR-42 in Treating Patients With Advanced or Relapsed Multiple Myeloma, Chronic Lymphocytic Leukemia, or Lymphoma

Brief Summary

Trial Health

Trial Health Score

Trial Relationships

Study Timeline

Study Start

First Submitted

First Posted

Primary Completion

Study Completion

Conditions

Outcome Measures

Primary Outcomes (1)

Secondary Outcomes (3)

Study Arms (2)

Arm I (Hematologic Malignancies)

Arm II (Solid Tumors)

Interventions

Eligibility Criteria

Sponsors & Collaborators

Study Sites (1)

Related Publications (3)

Related Links

MeSH Terms

Conditions

Interventions

Condition Hierarchy (Ancestors)

Intervention Hierarchy (Ancestors)

Study Officials

Study Design

Study Record Dates

Locations

Brief Summary

Trial Health

Trial Health Score

Trial Relationships

Related Scientific Literature

Study Timeline

Study Start

First Submitted

First Posted

Primary Completion

Study Completion

Conditions

Outcome Measures

Primary Outcomes (1)

Secondary Outcomes (3)

Study Arms (2)

Arm I (Hematologic Malignancies)

Arm II (Solid Tumors)

Interventions

Eligibility Criteria

Sponsors & Collaborators

Study Sites (1)

Related Publications (3)

Related Links

MeSH Terms

Conditions

Interventions

Condition Hierarchy (Ancestors)

Intervention Hierarchy (Ancestors)

Study Officials

Study Design

Study Record Dates

Locations