SGN-30 and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Hodgkin's Lymphoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00337194
First received: June 13, 2006
Last updated: October 28, 2013
Last verified: October 2013
  Purpose

This randomized phase II trial is studying how well giving SGN-30 together with combination chemotherapy works in treating patients with relapsed or refractory Hodgkin's lymphoma. Monoclonal antibodies, such as SGN-30, can block cancer growth in different ways. Some find cancer cells and kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as gemcitabine, vinorelbine, and doxorubicin hydrochloride liposome, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving SGN-30 together with combination chemotherapy may kill more cancer cells.


Condition Intervention Phase
Adult Lymphocyte Depletion Hodgkin Lymphoma
Adult Mixed Cellularity Hodgkin Lymphoma
Adult Nodular Sclerosis Hodgkin Lymphoma
Recurrent Adult Hodgkin Lymphoma
Biological: monoclonal antibody SGN-30
Other: placebo
Drug: vinorelbine tartrate
Drug: pegylated liposomal doxorubicin hydrochloride
Drug: gemcitabine hydrochloride
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized Double-Blinded Placebo Controlled Phase II Study of the Anti-CD30 Antibody, SGN-30 (NSC #731636, IND # 100057), in Combination With Gemcitabine, Vinorelbine, and Pegylated Liposomal Doxorubicin (GVD) for Patients With Relapsed/Refractory Hodgkin Lymphoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Overall response (OR) rate [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    For each arm, the true OR rate and 95% exact confidence interval will be estimated.

  • Toxicity as assessed by Common Terminology Criteria for Adverse Events version 3.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    Summarized using frequency tables.

  • Time-to-progression (TTP) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Kaplan-Meier method will be used for analyzing TTP.

  • Overall survival (OS) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Kaplan-Meier method will be used for analyzing OS.


Secondary Outcome Measures:
  • Pharmacokinetic profile of SGN-30 [ Time Frame: At baseline on day 1 and at the last day of protocol therapy ] [ Designated as safety issue: No ]
  • Correlation between CD30 levels and response to treatment [ Time Frame: From baseline to up to 10 years ] [ Designated as safety issue: No ]
  • Incidence of HACA formation [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    The incidence of HACA formation and its confidence interval will be estimated.

  • Correlation of Fcy receptor with response to treatment [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Fisher's exact test with 2-sided α=0.05 will be used to compare the response probabilities.


Enrollment: 141
Study Start Date: April 2006
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (SGN-30, chemotherapy)
Patients receive monoclonal antibody SGN-30 IV over 2 hours, vinorelbine IV over 6-10 minutes, gemcitabine IV over 30 minutes, and pegylated doxorubicin HCl liposome IV over 90 minutes on days 1 and 8.
Biological: monoclonal antibody SGN-30
Given IV
Other Name: SGN-30
Drug: vinorelbine tartrate
Given IV
Other Names:
  • Eunades
  • navelbine ditartrate
  • NVB
  • VNB
Drug: pegylated liposomal doxorubicin hydrochloride
Given IV
Other Names:
  • CAELYX
  • Dox-SL
  • DOXIL
  • doxorubicin hydrochloride liposome
  • LipoDox
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Placebo Comparator: Arm II (placebo, chemotherapy)
Patients receive placebo IV over 2 hours, vinorelbine IV over 6-10 minutes, gemcitabine IV over 30 minutes, and pegylated doxorubicin HCl liposome IV over 90 minutes on days 1 and 8. (closed to accrual as of 12/4/07)
Other: placebo
Given IV
Other Name: PLCB
Drug: vinorelbine tartrate
Given IV
Other Names:
  • Eunades
  • navelbine ditartrate
  • NVB
  • VNB
Drug: pegylated liposomal doxorubicin hydrochloride
Given IV
Other Names:
  • CAELYX
  • Dox-SL
  • DOXIL
  • doxorubicin hydrochloride liposome
  • LipoDox
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the complete and partial response rates after treatment with monoclonal antibody SGN-30, gemcitabine, vinorelbine, and pegylated doxorubicin HCl liposome in patients with relapsed or refractory Hodgkin's lymphoma.

II. Assess the time to progression and overall survival of patients treated with this regimen.

III. Evaluate the toxicity of this regimen in these patients.

SECONDARY OBJECTIVES:

I. Determine the pharmacokinetic profile of SGN-30 when compared with GVD chemotherapy.

II. Correlate sCD30 levels with response to treatment. III. Determine the incidence of human anti-chimeric antibodies (HACA) formation following repetitive SGN-30 dosing.

IV. Correlate Fc gamma receptor polymorphisms with the response to treatment.

OUTLINE:

Part 1 (Closed 5/18/2007): Patients receive monoclonal antibody SGN-30 IV over 2 hours, vinorelbine IV over 6-10 minutes, gemcitabine IV over 30 minutes, and pegylated doxorubicin HCl liposome IV over 90 minutes on days 1 and 8. Treatment repeats every 21 days until 10 out of 16 patients complete 1 course in the absence of unacceptable toxicity. Subsequent patients receive treatment on part 2.

Part 2: Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive monoclonal antibody SGN-30 IV over 2 hours, vinorelbine IV over 6-10 minutes, gemcitabine IV over 30 minutes, and pegylated doxorubicin HCl liposome IV over 90 minutes on days 1 and 8.

**Treatment with SGN-30/placebo was stopped on 4/12/2007 due to pulmonary toxicity.**

Arm II (closed to accrual as of 12/4/07): Patients receive placebo IV over 2 hours, vinorelbine IV over 6-10 minutes, gemcitabine IV over 30 minutes, and pegylated doxorubicin HCl liposome IV over 90 minutes on days 1 and 8.

Treatment in both arms repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for up to 10 years.

  Eligibility

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

Inclusion Criteria:

  • Histologically confirmed CD30+ classical Hodgkin's lymphoma, including the following subtypes:

    • Nodular sclerosis
    • Lymphocyte-depleted
    • Lymphocyte-rich
    • Mixed cellularity
  • Original diagnostic specimen or specimen from relapse required Core needle biopsy allowed provided there is adequate tissue for primary diagnosis and immunophenotyping

    • Bone marrow biopsy allowed provided nodal biopsy is available
    • No fine needle aspirates
  • Relapsed or refractory disease after >= 1 prior therapy
  • Measurable disease, defined as any lesion that can be accurately measured in >= 1 dimension as >= 10 mm

    • Nonmeasurable or evaluable disease allowed provided measurable disease is present; nonmeasurable disease includes any of the following:
    • Bone lesions
    • Bone marrow involvement
    • Ascites
    • Pleural/pericardial effusion
    • Lymphangitis cutis/pulmonis
  • No nodular lymphocyte-predominant Hodgkin's lymphoma
  • ECOG performance status 0-2
  • Absolute neutrophil count >= 1,200/mm^3
  • Platelet count >= 100,000/mm^3
  • Creatinine =< 2.0 mg/dL
  • Bilirubin =< 2.0 mg/dL (in the absence of Gilbert's disease)
  • AST =< 2.0 times upper limit of normal
  • LVEF >= 45% by MUGA or ECHO
  • DLCO >= 50%
  • Not pregnant
  • Negative pregnancy test
  • No nursing during and for 6 months after completion of study treatment
  • Fertile patients must use effective contraception during and for 6 months after completion of study treatment
  • No uncontrolled angina
  • No myocardial infarction within the past 6 months
  • No New York Heart Association class II-IV congestive heart failure
  • At least 3 weeks since prior chemotherapy or radiotherapy and recovered
  • Prior autologous, allogeneic, or unrelated stem cell transplantation allowed
  • No prior anti-CD30 antibody, gemcitabine, vinorelbine, or pegylated doxorubicin HCl liposome
  • No other concurrent chemotherapy
  • No concurrent steroids or hormones

    • Steroids given for adrenal failure or hormones administered for nondisease-related conditions (e.g., insulin for diabetes) allowed
  • No concurrent dexamethasone, except as needed to treat monoclonal antibody SGN-30 or pegylated doxorubicin HCl liposome infusion reactions, or as an anti-emetic on the day of chemotherapy
  • No concurrent palliative radiotherapy
  • No concurrent pegfilgrastim
  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: NCT00337194

Locations
United States, Illinois
Cancer and Leukemia Group B
Chicago, Illinois, United States, 60606
Sponsors and Collaborators
Investigators
Principal Investigator: Kristie Blum Cancer and Leukemia Group B
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00337194     History of Changes
Other Study ID Numbers: NCI-2012-02822, NCI-2012-02822, CALGB-50502, CALGB-50502, U10CA031946
Study First Received: June 13, 2006
Last Updated: October 28, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma
Sclerosis
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Pathologic Processes
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Gemcitabine
Doxorubicin
Vinorelbine
Vinblastine
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents

ClinicalTrials.gov processed this record on July 29, 2014