A Clinical Study Using MEDI-551 in Adult Participants With Relapsed or Refractory Advanced B-Cell Malignancies

MedImmune

Status and phase: Completed; Phase 2; Phase 1

Conditions: B-cell Malignancies; Cancer

Treatments: Drug: MEDI-551; Drug: Rituximab

Study type: Interventional

Funder types: Industry

Identifiers

NCT00983619

2009-016378-34 (EudraCT Number)

MI-CP204

Details and patient eligibility

About

The purpose of this study is to determine the maximum tolerated dose of this drug (MEDI-551) in participants with advanced B-cell malignancies. Expansion to occur at maximum tolerated dose (MTD), or if not reached, at optimal biologic dose (OBD).

Full description

To determine the MTD or OBD of MEDI-551 in participants with relapsed or refractory advanced B-cell malignancies.

Enrollment: 136 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically confirmed CLL, DLBCL, FL, or MM;
• Karnofsky Performance Status >= 70;
• Life expectancy of >= 12 weeks;
• Prior radiation therapy provided exposure does not exceed an area of 25% of marrow space
• Adequate hematological function
• Adequate organ function

Exclusion criteria

• Any available standard line of therapy known to be life-prolonging or life-saving;
• No concurrent therapy or therapy within six weeks of first dose of MEDI-551 for treatment of cancer
• Previous therapy directed against CD19
• Vaccination (other than experimental cancer vaccine therapy) within 28 days prior to receiving the first dose of MEDI-551;
• History of other invasive malignancy within 5 years except for cervical carcinoma in situ (CIS), non-melanomatous carcinoma of the skin or ductal carcinoma in situ (DCIS) of the breast that have been surgically cured;
• Active infection requiring treatment
• Autologous stem cell transplantation within 4 months prior to study entry;
• Allogeneic stem cell transplantation or any other organ transplant;
• Ongoing >= Grade 2 toxicities from previous cancer therapies unless specifically allowed in the Inclusion/Exclusion criteria.
• Use of immunosuppressive medication other than steroids within 28 days before the first dose of MEDI-551;
• Use of immunosuppressive medication other than steroids within 28 days before the first dose of MEDI-551 (inhaled and topical corticosteroids are permitted);
• Documented current central nervous system involvement by leukemia or lymphoma;
• Pregnancy or lactation;
• Clinically significant abnormality on ECG.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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136 participants in 12 patient groups

Part A-MEDI-551 0.5 mg/kg

Experimental group

Description:

Participants will receive intravenous (IV) infusion of MEDI 551 0.5 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.

Treatment:

Drug: MEDI-551

Part A-MEDI-551 1 mg/kg

Experimental group

Description:

Participants will receive IV infusion of MEDI 551 1 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.

Treatment:

Drug: MEDI-551

Part A-MEDI-551 2 mg/kg

Experimental group

Description:

Participants will receive IV infusion of MEDI 551 2 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.

Treatment:

Drug: MEDI-551

Part A-MEDI-551 4 mg/kg

Experimental group

Description:

Participants will receive IV infusion of MEDI 551 4 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.

Treatment:

Drug: MEDI-551

Part A-MEDI-551 8 mg/kg

Experimental group

Description:

Participants will receive IV infusion of MEDI 551 8 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.

Treatment:

Drug: MEDI-551

Part A-MEDI-551 12 mg/kg

Experimental group

Description:

Participants will receive IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.

Treatment:

Drug: MEDI-551

Part B-MEDI-551 6 mg/kg

Experimental group

Description:

Participants will receive IV infusion of MEDI- 551 6 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.

Treatment:

Drug: MEDI-551

Part B-MEDI-551 12 mg/kg

Experimental group

Description:

Participants will receive IV infusion of MEDI- 551 12 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.

Treatment:

Drug: MEDI-551

Part B-MEDI-551 24 mg/kg

Experimental group

Description:

Participants will receive IV infusion of MEDI- 551 24 mg/kg weekly for 4 weeks during Cycle 1 (over 2 days on Day 1 and Day 2, and on Days 8, 15, and 22) and thereafter from Cycle 2, on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.

Treatment:

Drug: MEDI-551

Part C-MEDI-551 8 mg/kg + rituximab

Experimental group

Description:

Participants will receive IV infusion of MEDI- 551 8 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m\^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg will be administered on Day 1 of each 28-day cycle. The treatment will be continued until the participants experiences unacceptable toxicity, disease progression, reaches complete response or withdraws consent.

Treatment:

Drug: MEDI-551

Drug: Rituximab

Part C-MEDI-551 12 mg/kg + rituximab

Experimental group

Description:

Participants will receive IV infusion of MEDI- 551 12 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m\^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg will be administered on Day 1 of each 28-day cycle. The treatment will be continued until the participants experiences unacceptable toxicity, disease progression, reaches complete response or withdraws consent.

Treatment:

Drug: MEDI-551

Drug: Rituximab

Part D-MEDI-551 12 mg/kg

Experimental group

Description:

Participants will receive IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and thereafter Day 1 of 28- day cycles from Cycle 2 onwards. Treatment will be continued until the participants experiences unacceptable toxicity, disease progression, reaches CR or withdraws consent.

Treatment:

Drug: MEDI-551