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SGN-30 and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Hodgkin 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: September 30, 2014
Last verified: December 2012
  Purpose

This randomized phase II trial studies the side effects and how well giving monoclonal antibody SGN-30 together with combination chemotherapy works in treating patients with Hodgkin lymphoma that has returned after a period of improvement or did not respond to previous treatment. Monoclonal antibodies, such as SGN-30, may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as gemcitabine hydrochloride, vinorelbine tartrate, and pegylated liposomal doxorubicin hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving monoclonal antibody SGN-30 together with combination chemotherapy may kill more cancer cells and shrink tumors.


Condition Intervention Phase
Adult Lymphocyte Depletion Hodgkin Lymphoma
Adult Lymphocyte Predominant 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, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Double-Blinded Placebo Controlled Phase II Study of the Anti-CD30 Antibody, SGN-30 (NSC #731636), 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:
  • Number of participants with overall response (OR) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    The number of participants who respond (complete or partial) to treatment. Response was defined using the revised criteria for malignant lymphoma. Complete response (CR): complete disappearance of all detectable disease; partial response (PR): >= 50% reduction in sum of the product of diameters of indicator lesions.


Secondary Outcome Measures:
  • Event Free Survival (EFS) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Event free survival is the time from trial entry until progression, death, or termination of treatment due to nonresponse. Patients who went on to receive a stem cell transplant (SCT) were not censored from the EFS survival at the time of transplant and were only considered failures at the time of relapse or death from any cause. The median EFS with 95% confidence interval (CI) was estimated using the Kaplan Meier method.

  • Overall survival (OS) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    OS was defined as the time from registration to death of any cause. Surviving patients were censored at the date of last follow-up. The median OS with 95% CI was estimated using the Kaplan Meier method.


Other Outcome Measures:
  • Mean serum level of monoclonal antibody SGN-30 [ Time Frame: Up to day 21 of course 6 ] [ Designated as safety issue: No ]
    Compared with the profile estimated from single agent phase I and II studies.

  • sCD30 levels [ Time Frame: Up to day 21 of course 6 ] [ Designated as safety issue: No ]
    A 2-sided t-test with alpha = 0.05 will be used to compare sCD30 levels between responders (OR) and non-responders groups.

  • Incidence of HACA formation following repetitive monoclonal antibody SGN-30 dosing [ Time Frame: Up to day 21 of course 6 ] [ Designated as safety issue: No ]
    The incidence of HACA formation and its confidence interval will be estimated.

  • Fc gamma receptor polymorphisms [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Fisher's exact test with 2-sided alpha = 0.05 will be used to compare the response probabilities in patients with V/V, V/F, and F/F for each of Fc gamma RIIIa and Fc gamma RIIa.


Enrollment: 30
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)

Participants receive one of the following regimens every cycle depending on history of prior stem cell transplant. Cycle is 21 days.

No prior stem cell transplant:

SGN-30: 12 mg/kg IV days 1 & 8, vinorelbine: 20 mg/m^2 IV days 1 & 8, gemcitabine: 1000 mg/m^2 IV days 1 & 8, pegylated doxorubicin HCl liposome: 15 mg IV days 1 & 8.

Prior stem cell transplant SGN-30: 12 mg/kg IV days 1 & 8, vinorelbine: 15 mg/m^2 IV days 1 & 8, gemcitabine: 800 mg/m^2 IV days 1 & 8, pegylated doxorubicin HCl liposome: 10 mg IV days 1 & 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
Active Comparator: Arm II (placebo, chemotherapy)

Participants receive one of the following regimens every cycle depending on history of prior stem cell transplant. Cycle is 21 days.

No prior stem cell transplant:

SGN-30: 12 mg/kg IV days 1 & 8, vinorelbine: 20 mg/m^2 IV days 1 & 8, gemcitabine: 1000 mg/m^2 IV days 1 & 8, pegylated doxorubicin HCl liposome: 15 mg IV days 1 & 8.

Prior stem cell transplant SGN-30: 12 mg/kg IV days 1 & 8, vinorelbine: 15 mg/m^2 IV days 1 & 8, gemcitabine: 800 mg/m^2 IV days 1 & 8, pegylated doxorubicin HCl liposome: 10 mg IV days 1 & 8.

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. To determine the complete and partial response rates following treatment with the anti-cluster of differentiation (CD) 30 antibody, SGN-30 (monoclonal antibody SGN-30), and gemcitabine (gemcitabine hydrochloride), vinorelbine (vinorelbine tartrate), and pegylated liposomal doxorubicin (pegylated liposomal doxorubicin hydrochloride) (GVD) in patients with relapsed or refractory Hodgkin lymphoma (HL).

II. To assess time to progression and overall survival in patients treated with SGN-30 and GVD in patients with relapsed or refractory Hodgkin lymphoma (HL).

III. To evaluate the toxicity of SGN-30 in combination with GVD in patients with relapsed and refractory HL.

SECONDARY OBJECTIVES:

I. To determine the pharmacokinetic profile of SGN-30 when combined with GVD chemotherapy.

II. To correlate soluble (s) CD30 levels with response to treatment. III. To determine the incidence of human anti-chimeric antibodies (HACA) formation following repetitive SGN-30 dosing.

IV. To correlate Fc gamma receptor polymorphisms with response to treatment.

OUTLINE:

Part 1 (closed to accrual as of 5/18/2007): Patients receive monoclonal antibody SGN-30 intravenously (IV) over 2 hours, vinorelbine tartrate IV over 6-10 minutes, gemcitabine hydrochloride IV over 30 minutes, and pegylated doxorubicin hydrochloride 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 tartrate IV over 6-10 minutes, gemcitabine hydrochloride IV over 30 minutes, and pegylated doxorubicin hydrochloride liposome IV over 90 minutes on days 1 and 8.

Arm II (closed to accrual as of 12/4/07): Patients receive placebo IV over 2 hours, vinorelbine tartrate IV over 6-10 minutes, gemcitabine hydrochloride IV over 30 minutes, and pegylated doxorubicin hydrochloride 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.

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

After completion of study treatment, patients are followed up 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 documented CD30-positive classical Hodgkin lymphoma according to the World Health Organization (WHO) classification of lymphoid malignancies that is recurrent or refractory after at least one prior therapy

    • Note: Patients with nodular lymphocyte predominant HL are not eligible; all other subtypes including nodular sclerosis, lymphocyte-depleted, lymphocyte rich, and mixed cellularity HL may be enrolled
    • Core needle biopsies are acceptable if they contain adequate tissue for primary diagnosis and immunophenotyping; bone marrow biopsies as the sole means of diagnosis are not acceptable, but they may be submitted in conjunction with nodal biopsies; fine needle aspirates are not acceptable; if the original diagnostic specimen is not available, specimens obtained at relapse may be submitted; if multiple specimens are available, please submit the most recent; failure to submit pathology specimens within 60 days of patient registration will be considered a major protocol violation
  • Patients must have relapsed or refractory disease after at least one prior therapy, with at least a 3 week interval from the completion of the most recent chemotherapy or radiotherapy regimen; recovery to =< grade 1 from all toxicities related to the prior treatments is required; patients who have previously received a stem cell transplant are permitted to enroll on this study

    • Prior treatment with an anti-CD30 antibody, gemcitabine, vinorelbine, or pegylated liposomal doxorubicin is not permitted
  • No uncontrolled angina, no myocardial infarction (MI) within 6 months of study entry, and no New York Heart Association (NYHA) class II or greater congestive heart failure (CHF)
  • Baseline left ventricular ejection fraction (LVEF) by multi gated acquisition scan (MUGA) or echocardiogram (ECHO) must be >= 45%
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Measurable disease must be present on either physical examination or imaging studies; evaluable or non-measurable disease alone is not acceptable

    • Measurable disease is defined as any lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 10 mm
    • Non-measurable disease includes all other lesions, including small lesions (< 10 mm) and truly non-measurable lesions
    • Lesions that are considered non-measurable include the following:

      • Bone lesions (lesions, if present, should be noted)
      • Bone marrow involvement (if present, this should be noted)
      • Ascites
      • Pleural/pericardial effusion
      • Lymphangitis cutis/pulmonis
  • Pregnant or nursing women may not be enrolled; women of childbearing potential must have a negative serum or urine pregnancy test prior to registration; women and men of reproductive potential should agree to use an effective means of birth control
  • Corrected diffusion capacity of carbon monoxide (DLCO) >= 50%
  • Absolute neutrophil count (ANC) >= 1,200/uL
  • Platelet count >= 100,000/uL
  • Creatinine =< 2.0 mg/dL
  • Bilirubin =< 2.0 mg/dL

    • Absent a history of Gilbert's disease
  • Aspartate aminotransferase (AST) =< 2.0 x upper limits of normal
  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, P30CA014236
Study First Received: June 13, 2006
Last Updated: September 30, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on November 24, 2014