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Adult Nasal Type Extranodal NK/T-cell LymphomaPhase 1NCT01129193

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

A Phase 1 study testing Pharmacodynamic Studies, Fatigue Inventory and Pharmacogenomic studies in people with Adult Nasal Type Extranodal NK/T-cell Lymphoma and Anaplastic Large Cell Lymphoma, run by Amir Mortazavi at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Pharmacodynamic Studies, Fatigue Inventory and Pharmacogenomic studies
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
44 participants
Where
1 siteUnited States
Study dates
4 May 2010to 7 Jan 2017
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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
  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • The Ohio State University James Cancer Hospital

    Columbus, Ohio, 43210

Other trials in United States

About this study

Official title: Phase I Study of AR-42 in Relapsed Myeloma, Chronic Lymphocytic Leukemia, and Lymphoma

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To estimate the safety by estimating the maximum tolerated dose (MTD) and describe the dose limiting toxicity (DLT) of AR-42 administered orally three times weekly (Mon, Wed, and Fri preferred) each week for 3 weeks during each 28-day period to adults with advanced or recurrent chronic lymphocytic leukemia (CLL), lymphoma, or multiple myeloma (MM).

SECONDARY OBJECTIVES:

  1. To characterize the pharmacokinetics of AR-42 in this patient population. II. To analyze patient samples for descriptive information regarding AR-42 pharmacodynamic changes in this patient population.

III. To obtain pilot data regarding efficacy at the MTD as measured by partial and complete responses in each disease subgroup during protocol expansion in stage III.

OUTLINE:

Patients receive oral AR-42 three times weekly on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for at least 30 days.

Being tested
Pharmacodynamic Studies, Fatigue Inventory, Pharmacogenomic studies, AR-42
Medical subject headings
Lymphoma, Extranodal NK-T-Cell, Lymphoma, Large-Cell, Anaplastic, Immunoblastic Lymphadenopathy, Intraocular Lymphoma, Lymphoma, B-Cell, Marginal Zone, Lymphoma, T-Cell, Peripheral, Leukemia, Prolymphocytic, Burkitt Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Pharmacodynamic StudiesOther

    Also called correlative studies

    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.

  • Fatigue InventoryOther

    Also called quality-of-life assessmentBrief

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

  • 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.

  • 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).

Study groups in NCT01129193
Study groupRoleWhat they receive
Arm I (Hematologic Malignancies)ExperimentalPatients 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).
Receives: Other: Pharmacodynamic Studies; Other: Fatigue Inventory; Other: Pharmacogenomic studies; Drug: AR-42
Arm II (Solid Tumors)ExperimentalPatients 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).
Receives: Drug: AR-42

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Adverse events described using the NCI CTCAE criteria

    Measured: Up to 3 years

Secondary outcomes (3)

  1. Clinical benefit

    Measured: Up to 3 years

  2. Duration of response

    Measured: Up to 3 years

  3. Time to progression

    Measured: Up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 May 2010 (estimated)
  2. Study start4 May 2010
  3. Primary completion7 Jan 2017
  4. Study completion7 Jan 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
44 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01129193
Sponsor's protocol ID
OSU-09102
Other IDs
NCI-2010-01082, P30CA016058
Status last verified
May 2018
First submitted
17 May 2010
Last updated
4 Jun 2018
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 33492438

  • 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.

    PubMed 28270022

  • 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.

    PubMed 26943915

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Pharmacodynamic Studies, Fatigue Inventory and Pharmacogenomic studies in people with Adult Nasal Type Extranodal NK/T-cell Lymphoma and Anaplastic Large Cell Lymphoma, run by Amir Mortazavi at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 30 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adverse events described using the NCI CTCAE criteria (time frame: Up to 3 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01129193, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2018.

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