Study Evaluating The Safety And Tolerability Of Combination Therapy Inotuzumab Ozogamicin (CMC-544) And Rituximab

A Phase 1 Study Of Cmc-544 Administered In Combination With Rituximab In Subjects With B-cell Non-hodgkin's Lymphoma

To assess the tolerability and the initial safety profile of Inotuzumab Ozogamicin (CMC-544) in combination with Rituximab in patients with B-Cell Non-Hodgkin's lymphoma (NHL).

Study Overview

• Status: Completed
• Conditions: Lymphoma, B-Cell
• Intervention / Treatment: Drug: Inotuzumab Ozogamicin (CMC-544); Drug: Rituximab (Rituxan)

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Aichi, Japan, 466-8650
    • Nagoya Daini Red Cross Hospital
  • Kanagawa, Japan, 259-1193
    • Tokai University Hospital
  • Tokyo, Japan, 104-0045
    • National Cancer Center Hospital
  • Tokyo, Japan, 135-8550
    • Cancer Inst. Hp. of Japanese Foundation for Cancer Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• CD20 and CD22-positive, B-cell NHL which has progressed after 1 or 2 prior therapies.
• Prior therapy must have contained at least one dose of Rituximab therapy. Patients can not be refractory to Rituximab (refractory = PD under treatment or within 6 month
• Eastern Cooperative Oncology Group (ECOG) performance status: 0/ 1.
• Patients must not have received previous radioimmunotherapy.
• Patients tolerant to Rituximab.
• Patients must not have received chemotherapy, cancer immunosuppressive therapy, growth factors (except erythropoietin), or investigational agents within 28 days before first dose of test article.

Exclusion Criteria:

• Candidate for potentially curative therapies
• Subjects must not have received previous radioimmunotherapy.
• Subjects with autologous hematopoietic stem cell transplant within the last 6 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Inotuzumab Ozogamicin + Rituximab	Drug: Inotuzumab Ozogamicin (CMC-544); 1.8 mg/m2, IV on day 2 of each 28 day cycle; up to 8 cycles unless PD, unacceptable toxicity, or subject's refusal occurs.; Drug: Rituximab (Rituxan); 375 mg/m2, IV on day 1 of each 28 day cycle; up to 8 cycles unless PD, unacceptable toxicity, or subject's refusal occurs.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Dose-limiting Toxicities (DLT)	A DLT was defined as the following drug-related adverse event which occurred during the first 28 days: 1) Any National Cancer Institute (NCI) Grade 3 or 4 nonhematologic toxicity (except Grade 3 nausea or vomiting without optimal treatment), 2) Febrile neutropenia, 3) Grade 4 absolute neutrophil count lasting >=7 days, 4) Grade 4 thrombocytopenia lasting >=3 days, 5) Grade 3 or 4 thrombocytopenia associated with a bleeding episode requiring platelet transfusion, 6)Delayed recovery (to grade <=1 or baseline, except alopecia) from a drug-related toxicity that delayed the next dose >2 weeks	Up to 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Objective Response: Evaluable Population	Number of participants with objective response of complete response (CR), complete response unconfirmed (CRu), or partial response (PR). Objective response included subjects with CR, CRu, and PR. Response criteria for Non-Hodgkin's Lymphoma (NHL) were based on the 1999 NCI International Workshop to standardize response criteria for NHL. Per the criteria for Lymph node masses: CR, normal size; CRu, normal or >75% decrease in the sum of the products of the greatest diameters (SPD); PR, normal or >=50% decrease in the SPD.	Up to 8 cycles (1 cycle = 28 days)
Number of Participants With Objective Response: Intent-to-treat (ITT) Population	Number of participants with objective response of complete response (CR), complete response unconfirmed (CRu), or partial response (PR). Objective response included subjects with CR, CRu, and PR. Response criteria for Non-Hodgkin's Lymphoma (NHL) were based on the 1999 NCI International Workshop to standardize response criteria for NHL. Per the criteria for Lymph node masses: CR, normal size; CRu, normal or >75% decrease in the sum of the products of the greatest diameters (SPD); PR, normal or >=50% decrease in the SPD.	Up to 8 cycles (1 cycle = 28 days)
Progression-Free Survival (PFS)	The interval from the date of first administration of the test article until the first date on which relapsed disease, progressive disease (PD), or death was documented, censored at the last tumor evaluation date. Response criteria for Non-Hodgkin's Lymphoma (NHL) were based on the 1999 NCI International Workshop to standardize response criteria for NHL. Per the criteria for Lymph node masses: Relapse/PD, appearance of any new lesion or increased by >=50% in the size.	Up to 591 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Serum Concentration (Cmax) of CMC-544, Total Calicheamicin, and Anti-human CD22 Antibody (G544)	CMC-544 is composed of G544, an anti-human CD22 antibody, linked to a potent cytotoxic antitumor antibiotic called calicheamicin. CD22 is expressed on the malignant cells of the majority of B-lymphocyte malignancies.	Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544
Serum Decay Half-Life (t1/2) of CMC-544, Total Calicheamicin, and G544	The time measured for the serum concentration to decrease by one half.	Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CMC-544, Total Calicheamicin, and G544	AUClast= Area under the serum concentration versus time curve from time zero (pre-dose) to time of last measured concentration.	Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC∞) of CMC-544, Total Calicheamicin, and G544	AUC∞ = Area under the serum concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).	Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544
Clearance (CL) of CMC-544, Total Calicheamicin, and G544	The rate at which a drug is metabolized or eliminated by normal biological processes.	Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544
Volume of Distribution (Vss) of CMC-544, Total Calicheamicin, and G544	The theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.	Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544
Number of Participants With Positive Serum Antibody to Inotuzumab Ozogamicin (CMC-544)	Antibody responses to CMC-544	Up to 8 Cycles (1 cycle = 28 days)
Number of Participants With Positive Serum Antibody to Rituximab	Antibody responses to rituximab	Up to 8 Cycles (1 cycle = 28 days)

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Ogura M, Hatake K, Ando K, Tobinai K, Tokushige K, Ono C, Ishibashi T, Vandendries E. Phase I study of anti-CD22 immunoconjugate inotuzumab ozogamicin plus rituximab in relapsed/refractory B-cell non-Hodgkin lymphoma. Cancer Sci. 2012 May;103(5):933-8. doi: 10.1111/j.1349-7006.2012.02241.x. Epub 2012 Mar 20.

Study record dates

Study Major Dates

• Study Start (Actual): July 4, 2008
• Primary Completion (Actual): March 10, 2010
• Study Completion (Actual): March 10, 2010

Study Registration Dates

• First Submitted: July 25, 2008
• First Submitted That Met QC Criteria: July 29, 2008
• First Posted (Estimate): July 30, 2008

Study Record Updates

• Last Update Posted (Actual): March 15, 2019
• Last Update Submitted That Met QC Criteria: December 4, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: NHL; B-cell Non-Hodgkin's Lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Rituximab; Inotuzumab Ozogamicin
• Other Study ID Numbers: 3129K3-1104; B1931005 (Other Identifier: Alias Study Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No