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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Craig Hofmeister, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01129193
First received: May 17, 2010
Last updated: November 20, 2014
Last verified: November 2014
  Purpose

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.


Condition Intervention Phase
Adult Nasal Type Extranodal NK/T-cell Lymphoma
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-cell Lymphoma
Cutaneous B-cell Non-Hodgkin Lymphoma
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Hepatosplenic T-cell Lymphoma
Intraocular Lymphoma
Nodal Marginal Zone B-cell Lymphoma
Peripheral T-cell Lymphoma
Post-transplant Lymphoproliferative Disorder
Prolymphocytic Leukemia
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Adult Grade III Lymphomatoid Granulomatosis
Recurrent Adult Hodgkin Lymphoma
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Adult T-cell Leukemia/Lymphoma
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Mycosis Fungoides/Sezary Syndrome
Recurrent Small Lymphocytic Lymphoma
Refractory Chronic Lymphocytic Leukemia
Refractory Multiple Myeloma
Stage III Adult Burkitt Lymphoma
Stage III Adult Diffuse Large Cell Lymphoma
Stage III Adult Diffuse Mixed Cell Lymphoma
Stage III Adult Diffuse Small Cleaved Cell Lymphoma
Stage III Adult Hodgkin Lymphoma
Stage III Adult Immunoblastic Large Cell Lymphoma
Stage III Adult Lymphoblastic Lymphoma
Stage III Adult T-cell Leukemia/Lymphoma
Stage III Chronic Lymphocytic Leukemia
Stage III Cutaneous T-cell Non-Hodgkin Lymphoma
Stage III Grade 1 Follicular Lymphoma
Stage III Grade 2 Follicular Lymphoma
Stage III Grade 3 Follicular Lymphoma
Stage III Mantle Cell Lymphoma
Stage III Marginal Zone Lymphoma
Stage III Multiple Myeloma
Stage III Mycosis Fungoides/Sezary Syndrome
Stage III Small Lymphocytic Lymphoma
Stage IV Adult Burkitt Lymphoma
Stage IV Adult Diffuse Large Cell Lymphoma
Stage IV Adult Diffuse Mixed Cell Lymphoma
Stage IV Adult Diffuse Small Cleaved Cell Lymphoma
Stage IV Adult Hodgkin Lymphoma
Stage IV Adult Immunoblastic Large Cell Lymphoma
Stage IV Adult Lymphoblastic Lymphoma
Stage IV Adult T-cell Leukemia/Lymphoma
Stage IV Chronic Lymphocytic Leukemia
Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma
Stage IV Grade 1 Follicular Lymphoma
Stage IV Grade 2 Follicular Lymphoma
Stage IV Grade 3 Follicular Lymphoma
Stage IV Mantle Cell Lymphoma
Stage IV Marginal Zone Lymphoma
Stage IV Mycosis Fungoides/Sezary Syndrome
Stage IV Small Lymphocytic Lymphoma
Testicular Lymphoma
Waldenstrom Macroglobulinemia
Other: Pharmacodynamic Studies
Other: Fatigue Inventory
Other: Pharmacogenomic studies
Drug: AR-42
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of AR-42 in Relapsed Myeloma, Chronic Lymphocytic Leukemia, and Lymphoma

Resource links provided by NLM:


Further study details as provided by Ohio State University Comprehensive Cancer Center:

Primary Outcome Measures:
  • Adverse events described using the NCI CTCAE criteria [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Clinical benefit [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Time to progression [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: May 2010
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (Hematologic Malignancies)
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 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.

Other Name: correlative studies
Other: Fatigue Inventory
Brief Fatigue Inventory should take each patient approximately 5 minutes to fill out this survey per instance on day 1 of every cycle.
Other Name: quality-of-life assessmentBrief
Other: Pharmacogenomic studies
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.
Drug: AR-42
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).
Other Name: AR-42
Experimental: Arm II (Solid Tumors)
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
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).
Other Name: AR-42

Detailed Description:

PRIMARY OBJECTIVES:

I. 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:

I. 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion

  • 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

Exclusion

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01129193

Locations
United States, Ohio
The Ohio State University James Cancer Hospital
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Craig Hofmeister
Investigators
Principal Investigator: Craig Hofmeister The Ohio State University James Cancer Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Craig Hofmeister, Principal Investigator, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01129193     History of Changes
Other Study ID Numbers: OSU-09102, NCI-2010-01082
Study First Received: May 17, 2010
Last Updated: November 20, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Burkitt Lymphoma
Hodgkin Disease
Immunoblastic Lymphadenopathy
Intraocular Lymphoma
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Leukemia, Prolymphocytic
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Lymphoma
Lymphoma, B-Cell
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Extranodal NK-T-Cell
Lymphoma, Follicular
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Large-Cell, Anaplastic
Lymphoma, Large-Cell, Immunoblastic
Lymphoma, Mantle-Cell
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Lymphoma, T-Cell, Peripheral
Lymphomatoid Granulomatosis
Lymphoproliferative Disorders
Multiple Myeloma
Mycoses
Mycosis Fungoides
Neoplasms, Plasma Cell
Sezary Syndrome

ClinicalTrials.gov processed this record on November 20, 2014