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

NCT01902160 | Completed Phase 1

• 5 other identifiers: NCI-2013-0127313-0449467P30CA008748U01CA069856
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Recurrent Adult Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• MTD of temsirolimus, determined according to incidence of dose limiting toxicity, graded using the National Cancer Institute Common Terminology Criteria for Adverse v4.0

  Toxicity will be reported using the Cancer Therapy Evaluation Program Adverse Event Reporting System.

  21 days

Secondary Outcomes (2)

• Changes in cytokine levels

  Baseline to day 1 of course 2

• Overall response rate (sum of partial responses and complete responses) using the criteria developed by the International Harmonization Project for response assessment in lymphoma

  Up to 4 weeks

Study Arms (1)

Treatment (temsirolimus, brentuximab vedotin)

EXPERIMENTAL

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: Brentuximab Vedotin; Other: Laboratory Biomarker Analysis; Drug: Temsirolimus

Interventions

Brentuximab Vedotin DRUG

Given IV

Also known as: ADC SGN-35, Adcetris, Anti-CD30 Antibody-Drug Conjugate SGN-35, Anti-CD30 Monoclonal Antibody-MMAE SGN-35, Anti-CD30 Monoclonal Antibody-Monomethylauristatin E SGN-35, cAC10-vcMMAE, SGN-35

Treatment (temsirolimus, brentuximab vedotin)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (temsirolimus, brentuximab vedotin)

Temsirolimus DRUG

Given IV

Also known as: CCI-779, CCI-779 Rapamycin Analog, Cell Cycle Inhibitor 779, Rapamycin Analog, Rapamycin Analog CCI-779, Torisel

Treatment (temsirolimus, brentuximab vedotin)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Hodgkin Disease

Interventions

Brentuximab Vedotin; temsirolimus; Sirolimus

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Macrolides; Lactones; Organic Chemicals

Study Officials

• Alison Moskowitz

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2013
• First Posted: July 18, 2013
• Study Start: September 1, 2013
• Primary Completion: May 1, 2015
• Last Updated: November 9, 2015

Record last verified: 2015-11

Locations

US (1)