A Phase 2, Multicenter, Randomized, Open-label Study of MEDI-551 in Adults With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

MedImmune

Status and phase: Completed; Phase 2

Conditions: Diffuse Large B-Cell Lymphoma

Treatments: Drug: ICE; Drug: DHAP; Drug: MEDI-551 2 mg/kg; Procedure: Autologous Stem Cell Transplant (ASCT); Drug: Rituximab; Drug: MEDI-551 4 mg/kg

Study type: Interventional

Funder types: Industry

Identifiers

NCT01453205

CD-ON-MEDI-551-1088

Details and patient eligibility

About

The overall purpose of the study is to determine if MEDI-551, when used in combination with salvage chemotherapy, Ifosfamide-carboplatin-etoposide (ICE) or Dexamethasone-cytarabine (DHAP) in patients with relapsed or refractory DLBCL who are eligible for Autologous Stem Cell Transplant (ASCT), has superior efficacy compared to rituximab in the same population.

Enrollment: 187 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically confirmed aggressive B-cell DLBCL, including FL transforming to DLBCL & Grade III FL
• Relapsed from or refractory to at least one treatment containing rituximab or another anti-CD20 based immunotherapy combined with anthracycline- or anthracenedione-based chemotherapy
• Eligible for ASCT
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Life expectancy of ≥ 12 weeks
• Adequate hematological function

Exclusion criteria

• Any chemotherapy, radiotherapy, immunotherapy, biologic, investigational or hormonal therapy for treatment of lymphoma within 28 days prior to treatment
• Previous cancer therapy for DLBCL other than anthracycline- or anthracenedione based chemoimmunotherapy, monotherapy rituximab prior to first line therapy and/or as a maintenance therapy, or limited field radiotherapy
• Prior autologous or allogeneic SCT
• New York Heart Association ≥ Class II congestive heart failure; Clinically significant abnormality on ECG
• History of other invasive malignancy within 5 years except for localized/in situ, carcinomas such as cervical carcinoma in situ.
• Evidence of active infection
• Documented current central nervous system involvement by leukemia or lymphoma

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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187 participants in 3 patient groups

Rituximab+ ICE/DHAP

Active Comparator group

Description:

Participants will receive Rituximab in combination with ifosfamide + carboplatin + etoposide (ICE) or dexamethasone + cisplatin + cytarabine (DHAP) for 3 cycles (21-day cycles) and will followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). Rituximab (375 mg/m\^2) will be administered intravenous (IV) on 2 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of rituximab, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of rituximab, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.

Treatment:

Procedure: Autologous Stem Cell Transplant (ASCT)

Drug: DHAP

Drug: ICE

Drug: Rituximab

MEDI-551 2 mg/kg + ICE/DHAP

Experimental group

Description:

Participants will receive MEDI-551 (2 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and will be followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (2 mg/kg) will be administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.

Treatment:

Procedure: Autologous Stem Cell Transplant (ASCT)

Drug: DHAP

Drug: ICE

Drug: MEDI-551 2 mg/kg

MEDI-551 4 mg/kg + ICE/DHAP

Experimental group

Description:

Participants will receive MEDI-551 (4 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and will be followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (4 mg/kg) will be administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.

Treatment:

Procedure: Autologous Stem Cell Transplant (ASCT)

Drug: MEDI-551 4 mg/kg

Drug: DHAP

Drug: ICE