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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

May 17, 2010
November 20, 2014
May 2010
June 2015   (final data collection date for primary outcome measure)
Adverse events described using the NCI CTCAE criteria [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
Adverse events described using the NCI CTCAE criteria [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01129193 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Clinical benefit [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Time to progression [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
AR-42 in Treating Patients With Advanced or Relapsed Multiple Myeloma, Chronic Lymphocytic Leukemia, or Lymphoma
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.

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.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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

    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 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).
    Interventions:
    • Other: Pharmacodynamic Studies
    • Other: Fatigue Inventory
    • Other: Pharmacogenomic studies
    • Drug: 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).
    Intervention: Drug: AR-42
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
60
December 2015
June 2015   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01129193
OSU-09102, NCI-2010-01082
Yes
Craig Hofmeister, Ohio State University Comprehensive Cancer Center
Craig Hofmeister
National Cancer Institute (NCI)
Principal Investigator: Craig Hofmeister The Ohio State University James Cancer Hospital
Ohio State University Comprehensive Cancer Center
November 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP