Study of Carfilzomib and Vorinostat for Relapsed or Refractory Lymphoma

NCT01276717 | Completed Phase 1 DMC

• 1 other identifier: 32833
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Lymphoma

Outcome Measures

Primary Outcomes (1)

• Number of Participants who experience Adverse Events as a Measure of Safety and Tolerability

  Determine the recommended phase II doses for the combination of carfilzomib and vorinostat in patients with relapsed or refractory B cell lymphoma.

  From date of study entry until the 30 days after the last dose of study treatment.

Secondary Outcomes (1)

• Number of Participants who Respond to Treatment

  From the date of completion of first cycle of treatment until the date of best response to treatment, as determined by restaging scans

Study Arms (1)

Vorinostat + Carfilzomib

EXPERIMENTAL

Drug: Drug: Carfilzomib; Drug: Vorinostat

Interventions

Drug: Carfilzomib DRUG

Carfilzomib 30 minutes infusion daily for days 1, 2, 8, 9, 15, 16, Every 28 days. A maximum of 13 cycles will be administered.

Also known as: PR-171

Vorinostat + Carfilzomib

Vorinostat DRUG

Vorinostat by mouth twice daily on days 1, 2, 3, 8, 9, 10, 15, 16 and 17. Maximum 13 cycles.

Also known as: Zolinza®

Vorinostat + Carfilzomib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Rochester: lead
• Massey Cancer Center: collaborator

Study Sites (2)

University of Rochester

Rochester, New York, 14642, United States

Location

Virginia Commonwealth University Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

MeSH Terms

Conditions

Lymphoma

Interventions

carfilzomib; Vorinostat

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Study Officials

• Jonathan Friedberg, M.D.

  University of Rochester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 10, 2010
• First Posted: January 13, 2011
• Study Start: January 1, 2011
• Primary Completion: July 1, 2013
• Study Completion: January 1, 2015
• Last Updated: December 3, 2015

Record last verified: 2015-12

Locations

US (2)