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

• Status: Completed
• Trial end date: 2017-01-07
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Amir Mortazavi; Craig Hofmeister
• Collaborators: Arno Therapeutics; National Cancer Institute (NCI)

Criteria

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.