Temsirolimus and Brentuximab Vedotin in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01902160
First received: July 15, 2013
Last updated: September 16, 2014
Last verified: June 2014
  Purpose

This phase I trial studies the side effects and best dose of temsirolimus when given together with brentuximab vedotin in treating patients with Hodgkin lymphoma that has returned or has not responded to treatment. Temsirolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Biological therapies, such as brentuximab vedotin, may stimulate the immune system in different ways and stop cancer cells from growing. Giving temsirolimus with brentuximab vedotin may work better in treating patients with Hodgkin lymphoma.


Condition Intervention Phase
Recurrent Adult Hodgkin Lymphoma
Drug: temsirolimus
Drug: brentuximab vedotin
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Study of Brentuximab Vedotin in Combination With Temsirolimus in Relapsed and Refractory Hodgkin Lymphoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • MTD of temsirolimus, determined according to incidence of dose limiting toxicity, graded using the National Cancer Institute Common Terminology Criteria for Adverse v4.0 [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
    Toxicity will be reported using the Cancer Therapy Evaluation Program Adverse Event Reporting System.


Secondary Outcome Measures:
  • Overall response rate (sum of partial responses and complete responses) using the criteria developed by the International Harmonization Project for response assessment in lymphoma [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: No ]
  • Changes in cytokine levels [ Time Frame: Baseline to day 1 of course 2 ] [ Designated as safety issue: No ]
    Descriptive statistics will be used to analyze the impact of cytokine levels on treatment response. Mean, standard deviation, median and range will be reported. Logistic regression will be used to evaluate the effects of the levels of serum cytokines/growth factors on treatment response.


Estimated Enrollment: 18
Study Start Date: September 2013
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (temsirolimus, brentuximab vedotin)
Patients receive temsirolimus IV over 30-60 minutes on days 1 and 8 or days 1, 8, and 15 and brentuximab vedotin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 16 courses in the absence of disease progression or unacceptable toxicity.
Drug: temsirolimus
Given IV
Other Names:
  • CCI-779
  • cell cycle inhibitor 779
  • Torisel
Drug: brentuximab vedotin
Given IV
Other Names:
  • Adcetris
  • anti-CD30 ADC SGN-35
  • anti-CD30 antibody-drug conjugate SGN-35
  • antibody-drug conjugate SGN-35
  • SGN-35
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose (MTD) of temsirolimus in combination with brentuximab vedotin in patients with relapsed and refractory Hodgkin lymphoma.

II. To assess the safety of brentuximab vedotin in combination with temsirolimus in patients with relapsed and refractory Hodgkin lymphoma.

III. To assess the toxicity profile of this regimen in the above patients.

SECONDARY OBJECTIVES:

I. Determine the overall response rate (ORR) to the combination of brentuximab vedotin and temsirolimus in relapsed and refractory Hodgkin lymphoma.

II. Evaluate the role of inflammatory markers, such as interleukin (IL)-6, IL-1, tumor necrosis factor alpha (TNF alpha), and IL-10, as early predictors of treatment response.

OUTLINE: This is a dose-escalation study of temsirolimus.

Patients receive temsirolimus intravenously (IV) over 30-60 minutes on days 1 and 8 or days 1, 8, and 15 and brentuximab vedotin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 16 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 4 weeks.

  Eligibility

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

Inclusion Criteria:

  • Patients must have histologically confirmed cluster of differentiation (CD)30 positive relapsed or refractory Hodgkin lymphoma
  • Measurable disease, defined as at least one lesion > 1.5 cm, in the greatest transverse diameter
  • Patients must have failed autologous stem cell transplant or at least 2 prior cytotoxic regimens for Hodgkin lymphoma
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Life expectancy of greater than 3 months
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin within normal institutional limits or < 3 x the upper limit of normal in patients with Gilbert's disease
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 × institutional upper limit of normal
  • Creatinine =< 1.5 x institutional upper limit of normal OR creatinine clearance >= 40 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Patients must have no evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 92% while breathing room air
  • Patients must have forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) > 60% by pulmonary function test (PFT), unless due to large mediastinal mass from Hodgkin's lymphoma (HL); carbon monoxide diffusion capacity (DLCO), FEV1, and FVC all > 50% predicted value
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of temsirolimus and brentuximab vedotin administration
  • Ability to understand and the willingness to sign a written informed consent document
  • Fasting serum cholesterol =< 300 mg/dL OR =< 7.75 mmol/L AND fasting triglycerides =< 2.5 x upper limit of normal (ULN); NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication
  • Patients with known human immunodeficiency virus (HIV) infection must have CD4 count greater than 200; anti-retroviral agents that induce or inhibit cytochrome P450 (CYP)3A4 activity are not allowed

Exclusion Criteria:

  • Patients who are eligible for autologous stem cell transplant unless they refuse to receive autologous stem cell transplant
  • Patients who have had chemotherapy or radiotherapy within 3 weeks of registration or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier; Note: patients are considered enrolled on the study after protocol registration and not after signing consent
  • Patients who have received brentuximab vedotin within 6 months of enrolling on the study
  • Patients who are receiving any other investigational agents
  • Patients with known cerebral or meningeal involvement by lymphoma should be excluded from this clinical trial
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to temsirolimus or brentuximab vedotin
  • Patients receiving any medications or substances that are inhibitors or inducers of CYP3A4 are ineligible
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled diabetes, clinically significant pneumonitis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with temsirolimus and brentuximab vedotin
  • Previous primary progression or grade 3 toxicity on treatment with brentuximab vedotin
  • Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent, except corticosteroids with a daily dosage equivalent to prednisone =< 20 mg; topical or inhaled corticosteroids are allowed
  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: NCT01902160

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Alison J. Moskowitz    212-639-4839    Moskowia@mskcc.org   
Principal Investigator: Alison J. Moskowitz         
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Alison J. Moskowitz    212-639-4839    moskowia@mskcc.org   
Principal Investigator: Alison J. Moskowitz         
Sponsors and Collaborators
Investigators
Principal Investigator: Alison Moskowitz Memorial Sloan-Kettering Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01902160     History of Changes
Other Study ID Numbers: NCI-2013-01273, NCI-2013-01273, 13-044, 9467, U01CA069856, P30CA008748
Study First Received: July 15, 2013
Last Updated: September 16, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Hodgkin Disease
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antibodies
Sirolimus
Everolimus
Antibodies, Monoclonal
Immunoconjugates
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents

ClinicalTrials.gov processed this record on September 18, 2014