SGN-30 and Combination Chemotherapy in Treating Patients With Newly Diagnosed Anaplastic Large Cell Lymphoma

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Terminated
• CT.gov ID: NCT00365274
• Collaborator: (none)
• Enrollment: 6
• Location: 1
• Arm: 1
• Duration (Months): 45
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Anaplastic Large Cell Lymphoma	Drug: Cyclophosphamide; Drug: Doxorubicin hydrochloride; Drug: vincristine sulfate; Drug: prednisone; Drug: SGN-30	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. 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).

2. Determine the safety of combining monoclonal antibody SGN-30 with CHOP chemotherapy.

SECONDARY OBJECTIVES:

1. Determine whether monoclonal antibody SGN-30 can induce apoptosis of ALCL cells in vivo.

2. Determine the response duration in patients treated with this regimen.

3. Correlate response with pretreatment serum CD30 levels.

4. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of SGN-30 in Combination With CHOP in Anaplastic Large Cell Lymphoma
• Study Start Date: Aug 1, 2006
• Actual Primary Completion Date: May 1, 2010
• Actual Study Completion Date: May 1, 2010

Arms and Interventions

Arm

Intervention/Treatment

Experimental: 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.

Drug: Cyclophosphamide; Given IV 750 mg/m^2 day 1; Other Names: CPM CTX Cytoxan Endoxan Endoxana ; Drug: Doxorubicin hydrochloride; Given 50 mg/m^2 IV day 1; Other Names: ADM ADR Adria Adriamycin PFS Adriamycin RDF ; Drug: vincristine sulfate; Given 1.4 mg/m^2 IV; Other Names: leurocristine sulfate VCR Vincasar PFS ; Drug: prednisone; 100 mg orally daily days 1 - 5; Other Names: DeCortin Deltra ; Drug: SGN-30; 12 mg/kg weekly IV over 2 hours once weekly for 3 weeks.; Other Names: Monoclonal antibody SGN-30 monotherapy

Outcome Measures

Primary Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	M D Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Michelle Fanale, MD, UT MD Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• The University of Texas MD Anderson Cancer Center official website

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00365274
• Other Study ID Numbers: NCI-2009-00162; 2005-0627; N01CM62202; N01CM17003
• First Posted: Aug 17, 2006
• Last Update Posted: Jun 2, 2014
• Last Verified: Nov 1, 2013

• Keywords provided by National Cancer Institute (NCI): 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
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, Large-Cell, Anaplastic; Prednisone; Cyclophosphamide; Doxorubicin; Liposomal doxorubicin; Vincristine; Brentuximab Vedotin

Study Results

Participant Flow

Recruitment Details	Recruitment Period: August 9, 2006 to February 26, 2009. All recruitment was done in medical clinics.
Pre-assignment Detail	The six participants were registered at UT MD Anderson Cancer Center prior to early study termination although recruitment was open to multi-centers.

Arm/Group Title	SGN-30 + Combination Chemotherapy
Arm/Group Description	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.
Period Title: Overall Study
STARTED	6
COMPLETED	6
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	SGN-30 + Combination Chemotherapy
Arm/Group Description	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.
Overall Participants	6
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	36
Sex: Female, Male (Count of Participants)
Female	3 50%
Male	3 50%
Region of Enrollment (participants) [Number]
United States	6 100%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SGN-30 + Combination Chemotherapy
Arm/Group Description	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.
Measure Participants	6
Complete Response	83 1383.3%
Partial Response	17 283.3%

Adverse Events

Time Frame	2 years and 11 months
Arm/Group Title	SGN-30 + Combination Chemotherapy
Arm/Group Description	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.
All Cause Mortality
	SGN-30 + Combination Chemotherapy
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	SGN-30 + Combination Chemotherapy
	Affected / at Risk (%)	# Events
Total	0/6 (0%)
Other (Not Including Serious) Adverse Events
	SGN-30 + Combination Chemotherapy
	Affected / at Risk (%)	# Events
Total	5/6 (83.3%)
Blood and lymphatic system disorders
Elevated ALT, SGPT	1/6 (16.7%)
Elevated Bilirubin	1/6 (16.7%)
Elevated Hemoglobin	1/6 (16.7%)
Hyperglycemia	2/6 (33.3%)
Hypoglycemia	1/6 (16.7%)
Elevated Leukocytes	3/6 (50%)
Elevated Neutrophils (ANC/AGC)	2/6 (33.3%)
Elevated Platelets	1/6 (16.7%)
Eye disorders
Blurred Vision	2/6 (33.3%)
Ocular/visual (other)	1/6 (16.7%)
Watery Eye	2/6 (33.3%)
Gastrointestinal disorders
Constipation	2/6 (33.3%)
Diarrhea	3/6 (50%)
Dry Mouth	1/6 (16.7%)
Nausea	2/6 (33.3%)
Vomiting	2/6 (33.3%)
General disorders
Fatigue	3/6 (50%)
Infections and infestations
Fever without neutropenia	2/6 (33.3%)
Investigations
Edema: head and neck	1/6 (16.7%)
Rigors/chills	1/6 (16.7%)
Musculoskeletal and connective tissue disorders
Pain	4/6 (66.7%)
Nervous system disorders
Dizziness	2/6 (33.3%)
Neuropathy: motor	1/6 (16.7%)
Neuropathy: sensory	2/6 (33.3%)
Psychiatric disorders
Insomnia	1/6 (16.7%)
Memory impairment	2/6 (33.3%)
Mood alteration (depression)	1/6 (16.7%)
Reproductive system and breast disorders
Hot flashes	1/6 (16.7%)
Respiratory, thoracic and mediastinal disorders
Allergic Rhinitis	1/6 (16.7%)
Cough	1/6 (16.7%)
Dysphagia	1/6 (16.7%)
Dyspnea	2/6 (33.3%)
Mucositis, oral cavity	4/6 (66.7%)
Skin and subcutaneous tissue disorders
Dry Skin	1/6 (16.7%)
Pruritus	1/6 (16.7%)
Rash/desquamation	1/6 (16.7%)
Sweating	1/6 (16.7%)

Limitations/Caveats

[Not Specified]

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.