Anaplastic Large Cell Lymphoma
Conditions
Keywords
non-Hodgkin's lymphoma, NHL, murine monoclonal antibody, mAb, SGN-30, CHOP, Cyclophosphamide, Doxorubicin Hydrochloride, Vincristine, Prednisone, anaplastic large cell lymphoma, Lymphoma, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin, Lymphoma, Large-Cell, Anaplastic, Neoplasms by Histologic Type, Neoplasms, Lymphoproliferative Disorders, Lymphatic Diseases, Immunoproliferative Disorders, Immune System Diseases, Lymphoma, B-Cell, Lymphoma, T-Cell, Antibodies, Antibodies, Monoclonal, Immunologic Factors, Physiological Effects of Drugs, Pharmacologic Actions, Immunosuppressive Agents, Antirheumatic Agents, Therapeutic Uses, Antineoplastic Agents, Alkylating, Alkylating Agents, Molecular Mechanisms of Pharmacological Action, Antineoplastic Agents, Myeloablative Agonists, Antibiotics, Antineoplastic
Brief summary
This phase II trial is studying how well giving SGN-30 together with combination chemotherapy works in treating patients with newly diagnosed anaplastic large cell lymphoma. Monoclonal antibodies, such as SGN-30, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy 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
Detailed description
PRIMARY OBJECTIVES: I. Determine the efficacy of monoclonal antibody SGN-30 in combination with cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (CHOP) in patients with newly diagnosed anaplastic large cell lymphoma (ALCL). II. Determine the safety of combining monoclonal antibody SGN-30 with CHOP chemotherapy. SECONDARY OBJECTIVES: I. Determine whether monoclonal antibody SGN-30 can induce apoptosis of ALCL cells in vivo. II. Determine the response duration in patients treated with this regimen. III. Correlate response with pretreatment serum CD30 levels. IV. Determine response to single-agent monoclonal antibody SGN-30. OUTLINE: This is a multicenter study. Patients are stratified according to anaplastic large cell kinase (ALK) status (positive vs negative). Monoclonal antibody SGN-30 monotherapy: Patients receive monoclonal antibody SGN-30 IV over 2 hours once weekly for 3 weeks. Monoclonal antibody SGN-30 and CHOP chemotherapy: Beginning 1 week after completion of monoclonal antibody SGN-30 monotherapy, patients receive monoclonal antibody SGN-30 IV over 2 hours on day 1 and CHOP chemotherapy comprising cyclophosphamide IV over 1 hour, doxorubicin hydrochloride IV over 15 minutes, and vincristine IV over 15 minutes on day 1 and oral prednisone once daily on days 1-5. Treatment repeats every 21 days for 6-8 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for at least 5 years.
Interventions
DRUGCyclophosphamide
Given IV 750 mg/m\^2 day 1
DRUGDoxorubicin hydrochloride
Given 50 mg/m\^2 IV day 1
DRUGvincristine sulfate
Given 1.4 mg/m\^2 IV
DRUGprednisone
100 mg orally daily days 1 - 5
DRUGSGN-30
12 mg/kg weekly IV over 2 hours once weekly for 3 weeks.
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed systemic anaplastic large cell lymphoma (ALCL) * Tissue available for the determination of anaplastic large cell kinase (ALK) status \[t(2;5), ALK-NPM translocation\] prior to study entry * Prior steroids or topical treatments are allowed. Patients who are on chronic steroid therapy may receive concomitant steroids provided they have been on a stable dosage for at least 3 months prior to enrollment * Measurable disease, defined as \>= 1 lesion that can be accurately measured in \>= 1 dimension (longest diameter to be recorded) as \>= 20 mm by conventional techniques or as \>= 10 mm by spiral CT scan * The Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 OR Karnofsky PS 70-100% * White Blood Count (WBC) \>= 3,000/mm³ * Absolute neutrophil count \>= 1,500/mm³ * Platelet count \>= 100,000/mm³ (unless due to lymphoma \[i.e., splenomegaly and/or bone marrow involvement\]) * Bilirubin =\< 1.5 times upper limit of normal (ULN) * AST or ALT =\< 2.5 times ULN * Creatinine =\< 1.5 times ULN (unless due to lymphoma) OR creatinine clearance \>=60 mL/min * Left ventricular ejection fraction (LVEF) \>= 50% * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 3 months after completion of study treatment
Exclusion criteria
* No rapidly progressing disease or bulky disease, defined as a mass of \> 7 cm in largest diameter * No primary cutaneous ALCL * No known brain metastases * No concurrent combination antiretroviral therapy for HIV-positive patients * No history of allergic reactions attributed to compounds of similar chemical or biological composition to monoclonal antibody SGN-30 * No uncontrolled intercurrent illness, including, but not limited to, any of the following: * Ongoing or active infection * Symptomatic congestive heart failure * Unstable angina pectoris * Cardiac arrhythmia * Psychiatric illness or social situations that would preclude study compliance * No prior or other concurrent malignancy with \< 90% probability of survival at 5 years * No other concurrent anticancer agents or therapies * No prior chemotherapy for ALCL * No other concurrent investigational agents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to 5 years | Objective response rate (ORR) defined as the proportion of participants experiencing a Complete Response (CR) or Partial Response to a regimen of SGN-3- + CHOP using International Workshop Response Criteria (IWG) for Non-Hodgkin's Lymphomas (NHL). The IWG criteria (Cheson et al 2007) for a CR is a complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. A PR is at least a 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses, no increase should be observed in the size of other nodes, liver or spleen, and no new sites of disease should be observed. |
Countries
United States
Participant flow
Recruitment details
Recruitment Period: August 9, 2006 to February 26, 2009. All recruitment was done in medical clinics.
Pre-assignment details
The six participants were registered at UT MD Anderson Cancer Center prior to early study termination although recruitment was open to multi-centers.
Participants by arm
| Arm | Count |
|---|---|
| SGN-30 + Combination Chemotherapy Monoclonal antibody SGN-30 monotherapy: SGN-30 12 mg/kg weekly intravenously (IV) over 2 hours once weekly for 3 weeks.
SGN-30 and CHOP chemotherapy: Beginning 1 week after completion of monoclonal antibody SGN-30 monotherapy, SGN-30 12 mg/kg IV over 2 hours on day 1 and CHOP chemotherapy comprising cyclophosphamide IV over 1 hour, doxorubicin hydrochloride IV over 15 minutes, and vincristine IV over 15 minutes on day 1 and oral prednisone once daily on days 1-5. Treatment repeats every 21 days for 6-8 courses. | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | SGN-30 + Combination Chemotherapy |
|---|---|
| Age, Continuous | 36 years |
| Region of Enrollment United States | 6 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 5 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
Objective Response Rate (ORR)
Objective response rate (ORR) defined as the proportion of participants experiencing a Complete Response (CR) or Partial Response to a regimen of SGN-3- + CHOP using International Workshop Response Criteria (IWG) for Non-Hodgkin's Lymphomas (NHL). The IWG criteria (Cheson et al 2007) for a CR is a complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. A PR is at least a 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses, no increase should be observed in the size of other nodes, liver or spleen, and no new sites of disease should be observed.
Time frame: Up to 5 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SGN-30 + Combination Chemotherapy | Objective Response Rate (ORR) | Complete Response | 83 percentage of participants |
| SGN-30 + Combination Chemotherapy | Objective Response Rate (ORR) | Partial Response | 17 percentage of participants |