Ifosfamide, Carboplatin, Etoposide, and SGN-30 in Treating Young Patients With Recurrent Anaplastic Large Cell Lymphoma
Study Details
Study Description
Brief Summary
This phase I/II trial is studying the side effects and best dose of SGN-30 when given together with ifosfamide, carboplatin, and etoposide and to see how well they work in treating young patients with recurrent anaplastic large cell lymphoma. Drugs used in chemotherapy, such as ifosfamide, carboplatin, and etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
PRIMARY OBJECTIVES:
-
Define and describe the toxicities of monoclonal antibody SGN-30 alone (window) and in combination with ifosfamide, carboplatin, and etoposide (ICE) in pediatric patients with CD30-positive recurrent anaplastic large cell lymphoma.
-
Define, preliminarily, the antitumor activity of monoclonal antibody SGN-30 alone (window) and in combination with ICE in these patients.
SECONDARY OBJECTIVES:
-
Characterize the pharmacokinetics of monoclonal antibody SGN-30 in these patients.
-
Characterize the soluble CD30 concentrations at time of relapse in these patients.
-
Characterize the development of human antichimeric antibodies in these patients.
-
Measure minimal residual disease in these patients.
OUTLINE: This is a multicenter, pilot, phase I, dose-finding study of monoclonal antibody SGN-30 followed by a phase II study.
Patients receive monoclonal antibody SGN-30 IV alone on day 1 in weeks 1-8. Beginning in week 5, patients receive ICE chemotherapy comprising ifosfamide IV over 2 hours on days 1-3, carboplatin IV over 1 hour on day 1, and etoposide IV over 1 hour on days 1-3. Treatment with ICE repeats every 3 weeks for 6 courses** in the absence of unacceptable toxicity. Patients also receive intrathecal therapy comprising methotrexate, cytarabine, and hydrocortisone once on day 29 (week 5).
NOTE: **Patients planning to undergo bone marrow transplantation (BMT) receive 2 courses of ICE only and then undergo BMT off study.
Cohorts of 3-6 patients receive a pre-determined dose of monoclonal antibody SGN-30 with possible dose de-escalation to 1 dose level below in the event of ≥ 2 of 6 patients experience dose-limiting toxicity (DLT). The dose at which ≤ 1 of 6 patients experience DLT will be used in a phase II study.
After completion of study treatment, patients are followed periodically for 5 years.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment (monoclonal antibody therapy, chemotherapy) Patients receive monoclonal antibody SGN-30 IV alone on day 1 in weeks 1-8. Beginning in week 5, patients receive ICE chemotherapy comprising ifosfamide IV over 2 hours on days 1-3, carboplatin IV over 1 hour on day 1, and etoposide IV over 1 hour on days 1-3. Treatment with ICE repeats every 3 weeks for 6 courses** in the absence of unacceptable toxicity. Patients also receive intrathecal therapy comprising methotrexate, cytarabine, and hydrocortisone once on day 29 (week 5). Cohorts of 3-6 patients receive a pre-determined dose of monoclonal antibody SGN-30 with possible dose de-escalation to 1 dose level below in the event of ≥ 2 of 6 patients experience dose-limiting toxicity (DLT). The dose at which ≤ 1 of 6 patients experience DLT will be used in a phase II study. |
Biological: monoclonal antibody SGN-30
Given IV
Other Names:
Drug: therapeutic hydrocortisone
Given IT
Other Names:
Drug: ifosfamide
Given IV
Other Names:
Drug: carboplatin
Given IV
Other Names:
Drug: etoposide
Given IV
Other Names:
Drug: methotrexate
Given IT
Other Names:
Drug: cytarabine
Given IT
Other Names:
Other: pharmacological study
Correlative studies
Other Names:
Other: laboratory biomarker analysis
Correlative studies
|
Outcome Measures
Primary Outcome Measures
- Response [Week 4]
Anti tumor activity as assessed by computed tomography of neck/chest/abdomen/pelvis, positron emission tomography scan and/or gallium scan. Assessed by physical examination appropriate imaging studies. Bone marrow aspirate/biopsy must be normal and any macroscopic nodules in any organs detectable on imaging techniques should no longer be present. Gallium scans must be negative if initially positive.
Secondary Outcome Measures
- Pharmacokinetics of Monoclonal Antibody SGN-30 Assessed by Enzyme-linked Immunosorbent Assay (ELISA) Methods [At baseline, at weeks 1, 2, 5, 6, and 11]
- CD30 Concentrations Levels as Assessed by ELISA [At baseline]
Summarized using appropriate descriptive statistics and reported with associated exact 95% confidence intervals. Although the limited sample size precludes formal hypothesis testing, exploratory analysis of the association between soluble CD30 levels and PK parameters and response will be performed.
- Development of Human Antichimeric Antibodies by Using ELISA Method [Change from baseline to week 11]
Change in level from baseline to week 11 will be summarized using appropriate descriptive statistics and reported with associated exact 95% confidence intervals.
- Minimal Residual Disease by Using Southern Blotting or by Real-time Polymerase Chain Reaction (PCR) [At baseline and weeks 5 and 11]
NPM-ALK expression will be summarized using appropriate descriptive statistics and reported with associated exact 95% confidence intervals.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Histologically confirmed anaplastic large cell lymphoma
-
CD30-positive disease
-
Must be in first or second relapse
-
Measurable disease
-
No CNS disease
-
Karnofsky performance status (PS) 60-100% (> 16 years of age) OR Lansky PS 60-100% (≤ 16 years of age)
-
Absolute neutrophil count ≥ 1,000/mm³
-
Platelet count ≥ 100,000/mm³ (transfusion independent)
-
Platelet count ≥ 20,000/mm³ if bone marrow involvement (platelet transfusions allowed)
-
Hemoglobin ≥ 8.0 g/dL (RBC transfusion independent, unless bone marrow involvement)
-
Creatinine adjusted according to age as follows:
-
No greater than 0.4 mg/dL (≤ 5 months)
-
No greater than 0.5 mg/dL (6 months-11 months)
-
No greater than 0.6 mg/dL (1 year-23 months)
-
No greater than 0.8 mg/dL (2 years-5 years)
-
No greater than 1.0 mg/dL (6 years-9 years)
-
No greater than 1.2 mg/dL (10 years-12 years)
-
No greater than 1.4 mg/dL (13 years and over [female])
-
No greater than 1.5 mg/dL (13 years to 15 years [male])
-
No greater than 1.7 mg/dL (16 years and over [male])
-
Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min
-
Bilirubin ≤ 1.5 times upper limit of normal (ULN)
-
ALT < 3 times ULN
-
Albumin ≥ 2 g/dL
-
Not pregnant or nursing
-
Negative pregnancy test
-
Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment
-
No evidence of graft-vs-host disease
-
No documented active infection requiring antibiotics
-
No isolated bone recurrence
-
Recovered from prior therapy
-
At least 3 months since prior monoclonal antibody therapy
-
At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas)
-
At least 7 days since prior hematopoietic growth factor therapy
-
At least 3 months since prior biologic (antineoplastic) agents
-
At least 2 weeks since prior local palliative radiotherapy (small port)
-
At least 3 months since prior total-body irradiation, craniospinal radiotherapy, or radiotherapy to ≥ 50% of the pelvis
-
At least 6 weeks since other prior substantial bone marrow irradiation
-
At least 2 months since prior stem cell transplantation or rescue
-
No prior monoclonal antibody SGN-30
-
Concurrent steroids allowed provided dose has been stable or decreasing for the past 7 days
-
No concurrent immunosuppressive agents
-
No concurrent dexamethasone as an antiemetic
-
No other concurrent investigational drug or anticancer agents, including chemotherapy, radiotherapy, immunotherapy, or biological therapy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Children's Oncology Group | Philadelphia | Pennsylvania | United States | 19104 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: John Sandlund, Children's Oncology Group
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NCI-2009-00407
- NCI-2009-00407
- COG-ANHL06P1
- CDR0000486425
- ANHL06P1
- ANHL06P1
- U10CA098543
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Treatment (Monoclonal Antibody Therapy, Chemotherapy) |
|---|---|
| Arm/Group Description | Patients receive monoclonal antibody SGN-30 (dosage 12mg/kg) IV alone on day 1 in weeks 1-8. Beginning in week 5, patients receive ICE chemotherapy comprising ifosfamide IV (dosage 3g/m2) x 3 days over 2 hours on days 1-3, carboplatin IV (635mg/m2) over 1 hour on day 1, and etoposide IV (dosage 100/m2) over 1 hour on days 1-3. Treatment with ICE repeats every 3 weeks for 6 courses** in the absence of unacceptable toxicity. Patients also receive intrathecal therapy (dosage dependent on age) comprising methotrexate, cytarabine, and hydrocortisone once on day 29 (week 5). Cohorts of 3-6 patients receive a pre-determined dose of monoclonal antibody SGN-30 with possible dose de-escalation to 1 dose level below (dosage 8mg/kg) in the event of ≥ 2 of 6 patients experience dose-limiting toxicity (DLT). The dose at which ≤ 1 of 6 patients experience DLT will be used in a phase II study. |
| Period Title: Overall Study | |
| STARTED | 5 |
| COMPLETED | 0 |
| NOT COMPLETED | 5 |
Baseline Characteristics
| Arm/Group Title | Treatment (Monoclonal Antibody Therapy, Chemotherapy) |
|---|---|
| Arm/Group Description | Patients receive monoclonal antibody SGN-30 (dosage 12mg/kg) IV alone on day 1 in weeks 1-8. Beginning in week 5, patients receive ICE chemotherapy comprising ifosfamide IV (dosage 3g/m2) x 3 days over 2 hours on days 1-3, carboplatin IV (635mg/m2) over 1 hour on day 1, and etoposide IV (dosage 100/m2) over 1 hour on days 1-3. Treatment with ICE repeats every 3 weeks for 6 courses** in the absence of unacceptable toxicity. Patients also receive intrathecal therapy (dosage dependent on age) comprising methotrexate, cytarabine, and hydrocortisone once on day 29 (week 5). Cohorts of 3-6 patients receive a pre-determined dose of monoclonal antibody SGN-30 with possible dose de-escalation to 1 dose level below (dosage 8mg/kg) in the event of ≥ 2 of 6 patients experience dose-limiting toxicity (DLT). The dose at which ≤ 1 of 6 patients experience DLT will be used in a phase II study. |
| Overall Participants | 5 |
| Age (Count of Participants) | |
| <=18 years |
5
100%
|
| Between 18 and 65 years |
0
0%
|
| >=65 years |
0
0%
|
| Age (days) [Median (Inter-Quartile Range) ] | |
| Median (Inter-Quartile Range) [days] |
5655
|
| Sex: Female, Male (Count of Participants) | |
| Female |
0
0%
|
| Male |
5
100%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
0
0%
|
| Not Hispanic or Latino |
5
100%
|
| Unknown or Not Reported |
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
1
20%
|
| White |
3
60%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
1
20%
|
| Region of Enrollment (participants) [Number] | |
| United States |
4
80%
|
| Jordan |
1
20%
|
Outcome Measures
| Title | Response |
|---|---|
| Description | Anti tumor activity as assessed by computed tomography of neck/chest/abdomen/pelvis, positron emission tomography scan and/or gallium scan. Assessed by physical examination appropriate imaging studies. Bone marrow aspirate/biopsy must be normal and any macroscopic nodules in any organs detectable on imaging techniques should no longer be present. Gallium scans must be negative if initially positive. |
| Time Frame | Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Treatment (Monoclonal Antibody Therapy, Chemotherapy) |
|---|---|
| Arm/Group Description | Patients receive monoclonal antibody SGN-30 (dosage 12mg/kg) IV alone on day 1 in weeks 1-8. Beginning in week 5, patients receive ICE chemotherapy comprising ifosfamide IV (dosage 3g/m2) x 3 days over 2 hours on days 1-3, carboplatin IV (635mg/m2) over 1 hour on day 1, and etoposide IV (dosage 100/m2) over 1 hour on days 1-3. Treatment with ICE repeats every 3 weeks for 6 courses** in the absence of unacceptable toxicity. Patients also receive intrathecal therapy (dosage dependent on age) comprising methotrexate, cytarabine, and hydrocortisone once on day 29 (week 5). Cohorts of 3-6 patients receive a pre-determined dose of monoclonal antibody SGN-30 with possible dose de-escalation to 1 dose level below (dosage 8mg/kg) in the event of ≥ 2 of 6 patients experience dose-limiting toxicity (DLT). The dose at which ≤ 1 of 6 patients experience DLT will be used in a phase II study. |
| Measure Participants | 4 |
| Number [percent] |
50
|
| Title | Pharmacokinetics of Monoclonal Antibody SGN-30 Assessed by Enzyme-linked Immunosorbent Assay (ELISA) Methods |
|---|---|
| Description | |
| Time Frame | At baseline, at weeks 1, 2, 5, 6, and 11 |
Outcome Measure Data
| Analysis Population Description |
|---|
| These data were not collected to assess this study aim and will never be reported. |
| Arm/Group Title | Treatment (Monoclonal Antibody Therapy, Chemotherapy) |
|---|---|
| Arm/Group Description | Patients receive monoclonal antibody SGN-30 (dosage 12mg/kg) IV alone on day 1 in weeks 1-8. Beginning in week 5, patients receive ICE chemotherapy comprising ifosfamide IV (dosage 3g/m2) x 3 days over 2 hours on days 1-3, carboplatin IV (635mg/m2) over 1 hour on day 1, and etoposide IV (dosage 100/m2) over 1 hour on days 1-3. Treatment with ICE repeats every 3 weeks for 6 courses** in the absence of unacceptable toxicity. Patients also receive intrathecal therapy (dosage dependent on age) comprising methotrexate, cytarabine, and hydrocortisone once on day 29 (week 5). Cohorts of 3-6 patients receive a pre-determined dose of monoclonal antibody SGN-30 with possible dose de-escalation to 1 dose level below (dosage 8mg/kg) in the event of ≥ 2 of 6 patients experience dose-limiting toxicity (DLT). The dose at which ≤ 1 of 6 patients experience DLT will be used in a phase II study. |
| Measure Participants | 0 |
| Title | CD30 Concentrations Levels as Assessed by ELISA |
|---|---|
| Description | Summarized using appropriate descriptive statistics and reported with associated exact 95% confidence intervals. Although the limited sample size precludes formal hypothesis testing, exploratory analysis of the association between soluble CD30 levels and PK parameters and response will be performed. |
| Time Frame | At baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| These data were not collected to assess this study aim and will never be reported. |
| Arm/Group Title | Treatment (Monoclonal Antibody Therapy, Chemotherapy) |
|---|---|
| Arm/Group Description | Patients receive monoclonal antibody SGN-30 (dosage 12mg/kg) IV alone on day 1 in weeks 1-8. Beginning in week 5, patients receive ICE chemotherapy comprising ifosfamide IV (dosage 3g/m2) x 3 days over 2 hours on days 1-3, carboplatin IV (635mg/m2) over 1 hour on day 1, and etoposide IV (dosage 100/m2) over 1 hour on days 1-3. Treatment with ICE repeats every 3 weeks for 6 courses** in the absence of unacceptable toxicity. Patients also receive intrathecal therapy (dosage dependent on age) comprising methotrexate, cytarabine, and hydrocortisone once on day 29 (week 5). Cohorts of 3-6 patients receive a pre-determined dose of monoclonal antibody SGN-30 with possible dose de-escalation to 1 dose level below (dosage 8mg/kg) in the event of ≥ 2 of 6 patients experience dose-limiting toxicity (DLT). The dose at which ≤ 1 of 6 patients experience DLT will be used in a phase II study. |
| Measure Participants | 0 |
| Title | Development of Human Antichimeric Antibodies by Using ELISA Method |
|---|---|
| Description | Change in level from baseline to week 11 will be summarized using appropriate descriptive statistics and reported with associated exact 95% confidence intervals. |
| Time Frame | Change from baseline to week 11 |
Outcome Measure Data
| Analysis Population Description |
|---|
| These data were not collected to assess this study aim and will never be reported. |
| Arm/Group Title | Treatment (Monoclonal Antibody Therapy, Chemotherapy) |
|---|---|
| Arm/Group Description | Patients receive monoclonal antibody SGN-30 (dosage 12mg/kg) IV alone on day 1 in weeks 1-8. Beginning in week 5, patients receive ICE chemotherapy comprising ifosfamide IV (dosage 3g/m2) x 3 days over 2 hours on days 1-3, carboplatin IV (635mg/m2) over 1 hour on day 1, and etoposide IV (dosage 100/m2) over 1 hour on days 1-3. Treatment with ICE repeats every 3 weeks for 6 courses** in the absence of unacceptable toxicity. Patients also receive intrathecal therapy (dosage dependent on age) comprising methotrexate, cytarabine, and hydrocortisone once on day 29 (week 5). Cohorts of 3-6 patients receive a pre-determined dose of monoclonal antibody SGN-30 with possible dose de-escalation to 1 dose level below (dosage 8mg/kg) in the event of ≥ 2 of 6 patients experience dose-limiting toxicity (DLT). The dose at which ≤ 1 of 6 patients experience DLT will be used in a phase II study. |
| Measure Participants | 0 |
| Title | Minimal Residual Disease by Using Southern Blotting or by Real-time Polymerase Chain Reaction (PCR) |
|---|---|
| Description | NPM-ALK expression will be summarized using appropriate descriptive statistics and reported with associated exact 95% confidence intervals. |
| Time Frame | At baseline and weeks 5 and 11 |
Outcome Measure Data
| Analysis Population Description |
|---|
| These data were not collected to assess this study aim and will never be collected. |
| Arm/Group Title | Treatment (Monoclonal Antibody Therapy, Chemotherapy) |
|---|---|
| Arm/Group Description | Patients receive monoclonal antibody SGN-30 (dosage 12mg/kg) IV alone on day 1 in weeks 1-8. Beginning in week 5, patients receive ICE chemotherapy comprising ifosfamide IV (dosage 3g/m2) x 3 days over 2 hours on days 1-3, carboplatin IV (635mg/m2) over 1 hour on day 1, and etoposide IV (dosage 100/m2) over 1 hour on days 1-3. Treatment with ICE repeats every 3 weeks for 6 courses** in the absence of unacceptable toxicity. Patients also receive intrathecal therapy (dosage dependent on age) comprising methotrexate, cytarabine, and hydrocortisone once on day 29 (week 5). Cohorts of 3-6 patients receive a pre-determined dose of monoclonal antibody SGN-30 with possible dose de-escalation to 1 dose level below (dosage 8mg/kg) in the event of ≥ 2 of 6 patients experience dose-limiting toxicity (DLT). The dose at which ≤ 1 of 6 patients experience DLT will be used in a phase II study. |
| Measure Participants | 0 |
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Treatment (Monoclonal Antibody Therapy, Chemotherapy) | |
| Arm/Group Description | Patients receive monoclonal antibody SGN-30 (dosage 12mg/kg) IV alone on day 1 in weeks 1-8. Beginning in week 5, patients receive ICE chemotherapy comprising ifosfamide IV (dosage 3g/m2) x 3 days over 2 hours on days 1-3, carboplatin IV (635mg/m2) over 1 hour on day 1, and etoposide IV (dosage 100/m2) over 1 hour on days 1-3. Treatment with ICE repeats every 3 weeks for 6 courses** in the absence of unacceptable toxicity. Patients also receive intrathecal therapy (dosage dependent on age) comprising methotrexate, cytarabine, and hydrocortisone once on day 29 (week 5). Cohorts of 3-6 patients receive a pre-determined dose of monoclonal antibody SGN-30 with possible dose de-escalation to 1 dose level below (dosage 8mg/kg) in the event of ≥ 2 of 6 patients experience dose-limiting toxicity (DLT). The dose at which ≤ 1 of 6 patients experience DLT will be used in a phase II study. | |
All Cause Mortality |
||
| Treatment (Monoclonal Antibody Therapy, Chemotherapy) | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Treatment (Monoclonal Antibody Therapy, Chemotherapy) | ||
| Affected / at Risk (%) | # Events | |
| Total | 1/5 (20%) | |
| Gastrointestinal disorders | ||
| Ascites | 1/5 (20%) | 1 |
| Investigations | ||
| Neutrophil count decreased | 1/5 (20%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||
| Pleural effusion | 1/5 (20%) | 1 |
| Skin and subcutaneous tissue disorders | ||
| Skin and subcutaneous tissue disorders - Other, specify | 1/5 (20%) | 1 |
| Vascular disorders | ||
| Capillary leak syndrome | 1/5 (20%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Treatment (Monoclonal Antibody Therapy, Chemotherapy) | ||
| Affected / at Risk (%) | # Events | |
| Total | 3/5 (60%) | |
| Blood and lymphatic system disorders | ||
| Anemia | 3/5 (60%) | 3 |
| Gastrointestinal disorders | ||
| Mucositis oral | 1/5 (20%) | 1 |
| Infections and infestations | ||
| Infections and infestations - Other, specify | 1/5 (20%) | 1 |
| Investigations | ||
| Alanine aminotransferase increased | 2/5 (40%) | 2 |
| Aspartate aminotransferase increased | 1/5 (20%) | 1 |
| Blood bilirubin increased | 1/5 (20%) | 1 |
| Neutrophil count decreased | 1/5 (20%) | 1 |
| Platelet count decreased | 2/5 (40%) | 2 |
| White blood cell decreased | 2/5 (40%) | 2 |
| Metabolism and nutrition disorders | ||
| Hypercalcemia | 1/5 (20%) | 1 |
| Hyperglycemia | 2/5 (40%) | 2 |
| Hypoalbuminemia | 2/5 (40%) | 2 |
| Hypocalcemia | 1/5 (20%) | 1 |
| Hypokalemia | 2/5 (40%) | 2 |
| Hypomagnesemia | 2/5 (40%) | 2 |
| Hyponatremia | 1/5 (20%) | 1 |
| Hypophosphatemia | 1/5 (20%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Results Reporting Coordinator |
|---|---|
| Organization | Children's Oncology Group |
| Phone | 3522730558 |
| resultsreportingcoordinator@childrensoncologygroup.org |
- NCI-2009-00407
- NCI-2009-00407
- COG-ANHL06P1
- CDR0000486425
- ANHL06P1
- ANHL06P1
- U10CA098543