Study of Carfilzomib and Vorinostat for Relapsed or Refractory Lymphoma

• Status: Completed
• Trial end date: 2015-01-01
• Target enrollment: 0
• Participant gender: All

Summary

This will be a phase I study of carfilzomib in combination with vorinostat in patients with relapsed/refractory B-cell lymphomas. Combination therapy with proteosome inhibitor PR-171 and HDAC inhibitors is highly synergistic in primary DLBCL cells, and both classes of drugs can also synergize powerfully to induce cell death in bortezomib-resistant cells. The purpose of this study is to see if vorinostat can combine with carfilzomib and to safely find the recommended phase II dose.

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

Details

• Lead Sponsor: University of Rochester
• Collaborator: Massey Cancer Center
• Treatments: Vorinostat

Criteria

Inclusion Criteria:

• Histologically confirmed B-cell lymphomas, excluding CLL (Chronic Lymphocytic Leukemia), that is recurrent or refractory after at least one prior therapy and for which no other potentially curative therapy is available.

• Age ≥ 18 years

• ECOG Performance Status (PS) ≤ 2

• Laboratory parameters

• if SLL, lymphocyte count < 5,000/µL

• Absolute neutrophil count ≥ 1000/µL

• Platelets ≥ 75,000/µL

• Creatinine ≤ 1.5x upper limit of normal or calculated creatinine clearance > 40mL/min

• AST, ALT ≤ 2.5 x upper limit of normal (ULN)

• Bilirubin ≤ 2.0 mg/mL

• Serum potassium ≥ 3.5 mEq/L and serum magnesium ≥ 1.7 mEq/dL (electrolytes may be corrected with supplementation).

• PT < 1.5 x ULN and PTT < 1.2 x ULN (unless receiving therapeutic anticoagulation).

• Patient is, in investigator's opinion, willing and able to comply with the protocol requirements and offers written informed consent.

• Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control ( i.e., oral injectable hormonal methods; barrier methods such as intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence)for the duration of the study.

• Male subject agrees to use an acceptable method for contraception for the duration of study.

Exclusion Criteria:

• History of brain metastasis including leptomeningeal metastasis.

• Chemotherapy of radiotherapy within 3 weeks prior to entering the study.

• Prior histone deacetylase inhibitor as cancer treatment.

• Concurrent treatment with other investigational agents or cancer treatment.

• Unable to take oral medications.

• Active ischemic heart disease or congestive heart failure. If there is suspicion of cardiac disease, left ventricular ejection fraction (LVEF) must be ≥ 45%, otherwise study to evaluate EF is not required.

• Persistent blood pressure (BP) of ≥ 160/95 (three separate readings on different days).

• History of allergic reactions attributed to compounds of similar chemical or biological composition to carfilzomib and vorinostat.

• Known clinical significant infection including infection with human immunodeficiency virus (HIV), or active hepatitis B or C, requiring treatment.

• Serious medical or psychiatric illness likely to interfere with patient participation.

• Pregnant or nursing. Confirmation that a woman is not pregnant must be established by a negative serum pregnancy test result obtained at screening.

• Pregnancy testing is not required for post-menopausal or surgically sterilized women.

• No prior allogeneic stem cell transplant.

• Patients scheduled for any type of stem cell transplant within 4 weeks of treatment.

• Patients who have valproic acid for epilepsy can enroll, provided that they stopped drug at least 30 days prior to enrollment and they will be on a stable, effective dose of an alternative anti-seizure medication.