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

Lymphoma, B-Cell Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00724971
• Other study ID #: 3129K3-1104
• Secondary ID: B1931005
• Status: Completed
• Phase: Phase 1
• Start date: July 4, 2008
• Est. completion date: March 10, 2010

Study information

• Verified date: November 2018
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: March 10, 2010
• Est. primary completion date: March 10, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell

Intervention

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.
• 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.

Locations

Country	Name	City	State
Japan	Nagoya Daini Red Cross Hospital	Aichi
Japan	Tokai University Hospital	Kanagawa
Japan	Cancer Inst. Hp. of Japanese Foundation for Cancer Research	Tokyo
Japan	National Cancer Center Hospital	Tokyo

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC8) of CMC-544, Total Calicheamicin, and G544	AUC8 = Area under the serum concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (8). It is obtained from AUC (0 - t) plus AUC (t - 8).	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
Other	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
Other	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
Other	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)
Other	Number of Participants With Positive Serum Antibody to Rituximab	Antibody responses to rituximab	Up to 8 Cycles (1 cycle = 28 days)
Primary	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	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)
Secondary	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)
Secondary	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

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