Phase II Study of Ofatumumab Plus Ifosfamide, Carboplatin, Etoposide (ICE) or Dexamethasone, Cytarabine, Cisplatin (DHAP) Chemotherapy Regimen in Relapsed/ Refractory Diffuse Large B Cell Lymphoma (DLBCL)

NCT00823719 | Completed Phase 2 Results

• 1 other identifier: 110927
• Study Type: interventional
• Target: 61
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of ofatumumab used in combination with ifosfamide, carboplatin, etoposide (ICE) or dexamethasone, cytarabine, cisplatin (DHAP) salvage chemotherapy regimens in subjects with relapsed or refractory diffuse large B cell lymphoma (DLBCL) who are eligible for autologous stem cell transplant.

Conditions

Lymphoma, Large-Cell, Diffuse

Keywords

Salvage chemotherapy; relapsed; grade 3B follicular lymphoma; efficacy; safety; DHAP; ofatumumab; refractory; Non-Hodgkin's Lymphoma; Diffuse Large B Cell Lymphoma (DLBCL); Oncology; ICE; Transformed follicular lymphoma

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Overall Response (OR), as Assessed by the Investigator

  Responders with OR included participants with complete response (CR) and partial response (PR). This was based on adequate responses from the investigator assessment after the completion of treatment. CR: complete disappearance of all detectable clinical evidence of disease and disease-related symptoms. PR: at least a 50% decrease from baseline in the sum of the product of the diameters of target lesions.

  From Day 14 (Study Day 56) to Day 21 (approximately Study Day 63) of treatment Cycle 3, or earlier in the case of early withdrawal or missing response assessment for Cycle 3

Secondary Outcomes (15)

• Number of Participants With CR, as Assessed by the Investigator

  From Day 14 (Study Day 56) to Day 21 (approximately Study Day 63) of treatment Cycle 3, or earlier in the case of early withdrawal or missing response assessment for Cycle 3

• Number of Participants With the Ability to Mobilize at Least 2 Million Cluster of Differentiation (CD)34+ Cells Per Kilogram (kg) From Peripheral Blood

  During treatment Cycle 2 (Study Days 22-42) and/or Cycle 3 (Study Days 43-63)

• Progression-free Survival (PFS)

  From Day 14 (Study Day 56) to Day 21 (approximately Study Day 63) of treatment Cycle 3, or earlier in the case of early withdrawal or missing response assessment for Cycle 3

• Overall Survival

  From Day 14 (Study Day 56) to Day 21 (approximately Study Day 63) of treatment Cycle 3, or earlier in the case of early withdrawal or missing response assessment for Cycle 3

• Area Under the Concentration-time Curve From Time Zero to Infinity, AUC(0-inf), of Ofatumumab at the First Infusion (Cycle 1, Day 1) and the Last Infusion (Cycle 3)

  Cycle 1 Day 1 (Study Day 1; up to 1 week) and Cycle 3 (Study Day 43; up to 6 weeks)

Study Arms (1)

ofatumumab + DHAP or ICE chemotherapy regimen

EXPERIMENTAL

This study is a single arm study, but the Investigators are required to prospectively choose to treat all of their subjects with either ICE or DHAP chemotherapy regimens in combination with ofatumumab. Regardless of whether the subject receives ICE or DHAP chemotherapy, all subjects will receive the same ofatumumab regimen and dose.

Drug: ofatumumab + ICE; Drug: ofatumumab + DHAP

Interventions

ofatumumab + ICE DRUG

3 cycles of treatment will be administered. Each cycle will last 21 days. ofatumumab dose: cycle 1, day 1 - 1000 milligrams (mg); cycle 1, day 8 - 1000 mg; cycle 2, day 1 and cycle 3, day 1 - 1000 mg ICE regimen: ifosfamide + mesna - 5 grams (g)/meters squared (m\^2)/24 hours (hrs) continuous on day 2 of dosing cycle; carboplatin - AUC 5 (800 mg maximum) on day 2 of dosing cycle; etoposide - 100 mg/m\^2 on days 1, 2 and 3 of dosing cycle.

ofatumumab + DHAP or ICE chemotherapy regimen

ofatumumab + DHAP DRUG

3 cycles of treatment will be administered. Each cycle will last 21 days. ofatumumab dose: cycle 1, day 1 - 1000 mg; cycle 1, day 8 - 1000 mg; cycle 2, day 1 and cycle 3, day 1 - 1000 mg. DHAP regimen: dexamethasone - 40 mg on days 1, 2, 3, and 4 of dosing cycle; cisplatin - 100 mg/m\^2/24 hrs continuous on day 1 of dosing cycle; cytarabine - 2 g/m\^2 q12 hrs (2 doses) on day 2 of dosing cycle.

ofatumumab + DHAP or ICE chemotherapy regimen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects with CD20 positive aggressive non-Hodgkin's lymphoma (NHL) including DLBCL, transformed follicular lymphoma (FL) \& grade 3b FL.
• Refractory to, or relapsed following, first-line treatment with rituximab combined with anthracycline- or anthracenedione-based chemotherapy as defined by the protocol.
• Computed tomography (CT) with involvement of 2 or more clearly demarcated lesions with a long axis \> 1.5 centimeters (cm) and short axis ≥ 1.0 cm or 1 clearly demarcated lesion with a long axis \>2.0 cm and short axis ≥1.0 cm.
• Baseline \[18F\] fluorodeoxyglucose (FDG)-positron emission tomography (PET) scans must demonstrate positive lesions compatible with CT defined anatomical tumor sites.
• Age 18 yrs or older.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
• Eligible for high dose chemotherapy and autologous stem cell transplant (ASCT).
• Resolution of toxicities from first-line therapy to a grade that in the opinion of the investigator does not contraindicate study participation.
• Signed written informed consent.

You may not qualify if:

• Previous cancer therapy for lymphoma, with the exception of required rituximab/ anthracycline- or anthracenedione-based chemotherapy, monotherapy rituximab prior to first-line therapy and / or as a maintenance therapy, or limited field radiotherapy (as defined by the protocol).
• Any anti-cancer therapy, except limited field radiotherapy, within 2 weeks prior to start of study therapy.
• Chronic Glucocorticoid use (limited acute use is allowed and defined by the protocol).
• History of significant cerebrovascular disease.
• Abnormal/ inadequate white blood cell (WBC) count, liver, and kidney function.
• Clinically significant cardiac disease, active or chronic infections, serious significant diseases, other cancer within last 5 years.
• Known or suspected hypersensitivity to study treatments.
• Prior treatment with anti-CD20 monoclonal antibodies, at any time, or treated with other monoclonal antibodies within 3 months prior to start of study therapy, with the exception of rituximab in both instances.
• Inability to comply with the protocol activities.
• Pregnant or lactating women or female patients of child-bearing potential (or male patients with such partners) not willing to use adequate contraception during and up to 1 year following dosing completion.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Related Publications (1)

• Matasar MJ, Czuczman MS, Rodriguez MA, Fennessy M, Shea TC, Spitzer G, Lossos IS, Kharfan-Dabaja MA, Joyce R, Fayad L, Henkel K, Liao Q, Edvardsen K, Jewell RC, Fecteau D, Singh RP, Lisby S, Moskowitz CH. Ofatumumab in combination with ICE or DHAP chemotherapy in relapsed or refractory intermediate grade B-cell lymphoma. Blood. 2013 Jul 25;122(4):499-506. doi: 10.1182/blood-2012-12-472027. Epub 2013 May 21.

  PMID: 23692856 DERIVED

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Recurrence; Lymphoma, Non-Hodgkin; Neoplasms

Interventions

ofatumumab; Ice

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Water; Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds; Environment; Ecological and Environmental Phenomena; Biological Phenomena; Weather; Meteorological Concepts; Environment and Public Health

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2009
• First Posted: January 16, 2009
• Study Start: May 1, 2009
• Primary Completion: July 1, 2011
• Study Completion: September 1, 2011
• Last Updated: March 12, 2013
• Results First Posted: September 5, 2012

Record last verified: 2013-02