Phase 2
Completed N=119
Study Evaluating Inotuzumab Ozogamicin [CMC-544] Administered In Combination With Rituximab In Subjects With Non-Hodgkin's Lymphoma (NHL)
Source: ClinicalTrials.gov NCT00299494 ↗Enrolled (actual)
119
Serious AEs
23.5%
Results posted
Mar 2018
Primary outcomePrimary: Maximum Tolerated Dose (MTD) of Inotuzumab Ozogamicin in Combination With Rituximab (375 mg/m^2 ) — 1.8 mg/m^2
Summary
The purpose of the study is to determine the tolerability, the initial safety profile and maximum tolerated dose, and to obtain preliminary information on the antitumor activity of inotuzumab ozogamicin [CMC-544] in combination with rituximab in subjects with follicular, diffuse large B-Cell, or mantle cell NHL.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Tolerated Dose (MTD) of Inotuzumab Ozogamicin in Combination With Rituximab (375 mg/m^2 ) |
1.8 | — |
| PRIMARY Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) |
100; 100; 100; 100; 100; 100 | — |
| SECONDARY Percentage of Participants With Complete Response (CR), Unconfirmed CR (CRu), or Partial Response (PR) |
40; 100; 57.1; 94.1; 72.5; 20 | — |
| SECONDARY Kaplan-Meier Estimates of Progression Free Survival (PFS) |
1.7; NA; NA; NA; 17.1; 1.8 | — |
| SECONDARY Kaplan-Meier Estimates of the Probability of Being Progression Free at 6 Months |
0.4; 1.0; 0.6; 1.0; 0.7; 0.2 | — |
| SECONDARY Kaplan-Meier Estimates of Overall Survival (OS) |
7.4; NA; 16.9; NA; 58.3; 8.4 | — |
| SECONDARY Kaplan-Meier Estimates of the Probability of Survival at 6 Months |
0.6; 1.0; 0.7; 1.0; 0.9; 0.6 | — |
| SECONDARY Kaplan-Meier Estimates of Time to Tumor Progression (TTP) |
1.7; NA; NA; NA; 45.1; 1.7 | — |
| SECONDARY Kaplan-Meier Estimates of the Probability of Being Event Free at 6 Months |
0.4; 1.0; 0.7; 1.0; 0.7; 0.3 | — |
| SECONDARY Duration of Response (CR+CRu+PR) |
NA; NA; NA; NA; 43.2; 3.9 | — |
| SECONDARY Area Under the Serum Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 |
36030; 40550 | — |
| SECONDARY AUClast of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 |
6157; 9664; 17320 | — |
| SECONDARY Time of the Last Quantifiable Serum Concentration in a Dosing Interval (Tlast) of Inotuzumab Ozogamicin in Participants Receving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 |
44.2; 53.9; 137 | — |
| SECONDARY Area Under the Steady-state Serum Concentration-time Curve (AUCtau) of Inotuzumab Ozogamicin in Participants Receving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 |
18660; 35900; 38820 | — |
| SECONDARY Peak Serum Concentration (Cmax) of Inotuzumab Ozogamicin in Participants Receving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 |
600.2; 378.3; 519.2 | — |
| SECONDARY Time to Reach Maximum Concentration (Tmax) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 |
1.00; 1.08; 1.08 | — |
| SECONDARY Average Serum Concentration at Steady State (Cav) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 |
53.43; 57.77 | — |
| SECONDARY Minimum Observed Serum Trough Concentration (Cmin) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab+Rituximab on Dosing Day 30 and Day 58 |
0.0001196; 0 | — |
| SECONDARY Clearance (CL) of Serum Inotuzumab Ozogamicin in Participants Receiving Inotuzumab+Rituximab on Dosing Day 30 and Day 58 |
0.09855; 0.08743 | — |
| SECONDARY Steady-state Volume of Distribution (Vss) of Inotuzumab Ozogamicin in Serum in Participants Receiving Inotuzumab MTD+Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 |
4.860; 5.183 | — |
| SECONDARY MRT of Inotuzumab Ozogamicin in Serum in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 |
49.31; 59.24 | — |
| SECONDARY Serum Decay Half-Life (t1/2) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 |
40.15; 43.00 | — |
| SECONDARY AUCinf of Total Calicheamicin (Conjugated + Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 |
8437; 10060 | — |
| SECONDARY AUClast of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 |
1901; 6129; 6755 | — |
| SECONDARY Time of the Last Quantifiable Concentration in a Dosing Interval (Tlast) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 |
149; 312; 458 | — |
| SECONDARY Area Under the Steady-state Serum Concentration-time Curve (AUCtau) for Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30, and Day 58 |
3201; 7794; 9197 | — |
| SECONDARY Peak Serum Concentration (Cmax) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 |
54.36; 58.67; 64.43 | — |
| SECONDARY Time of Observed Maximum Concentration (Tmax) of Total Calicheamicin (Conjugated+Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 |
1.05; 1.26; 1.38 | — |
| SECONDARY Average Serum Concentration (Cav) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 |
11.60; 13.69 | — |
| SECONDARY Minimum Observed Serum Trough Concentration (Cmin) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 |
0.0001326; 0.0001350 | — |
| SECONDARY Clearance (CL) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 |
0.4353; 0.3799 | — |
| SECONDARY Steady-state Volume (Vss) of Total Calicheamicin (Conjugated Plus Unconjugated) Distribution in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 |
72.95; 75.81 | — |
| SECONDARY Mean Residence Time (MRT) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 |
167.5; 199.5 | — |
| SECONDARY Serum Decay Half-Life (t1/2) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 |
126.5; 176.0 | — |
| SECONDARY Area Under the Steady-state Serum Concentration-time Curve (AUClast) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 |
0.0009904; 0.002008; 0.005896 | — |
| SECONDARY Time of the Last Quantifiable Concentration in a Dosing Interval (Tlast) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 |
48.5; 4.00; 4.00 | — |
| SECONDARY Peak Serum Concentration (Cmax) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 |
0.0005608; 0.001153; 0.003250 | — |
| SECONDARY Time of Observed Maximum Concentration (Tmax) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin + Rituximab on Dosing Day 1, Day 30 and Day 58 |
1.38; 4.00; 3.42 | — |
| SECONDARY Minimum Observed Serum Trough Concentration (Cmin) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin+Rituximab on Dosing Day 30 and Day 58 |
0.0001588; 0.0001495 | — |
| SECONDARY Area Under the Serum Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m2 on Dosing Day 30 and Day 58 |
83270; 93760 | — |
| SECONDARY Area Under the Steady-state Concentration-time Curve (AUClast) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 |
25740; 61770; 72430 | — |
| SECONDARY Time of the Last Quantifiable Concentration in a Dosing Interval (Tlast) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 |
190; 310; 312 | — |
| SECONDARY Serum Decay Half-Life (t1/2) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab on Dosing Day 30 and Day 58 |
99.35; 103.5 | — |
| SECONDARY Area Under the Steady-state Serum Concentration-time Curve (AUCtau) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD+ Rituximab 375 mg/m^2 on Dosing Day 1, Day 30, and Day 58 |
40180; 80060; 91370 | — |
| SECONDARY Peak Concentration (Cmax) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 |
776.6; 700.4; 653.0 | — |
| SECONDARY Time to Reach Maximum Concentration (Tmax) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 |
1.05; 1.17; 3.79 | — |
| SECONDARY Average Serum Concentration (Cav) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 |
119.2; 136 | — |
| SECONDARY Minimum Observed Serum Trough Concentration (Cmin) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 |
0.0001190; 0 | — |
| SECONDARY Clearance (CL) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 |
0.04240; 0.03699 | — |
| SECONDARY Steady-state Volume (Vss) of Inotuzumab Ozogamicin Antibody Distribution in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 |
5.283; 4.952 | — |
Eligibility Criteria
Inclusion Criteria
- Subjects with CD20 and CD22-positive, follicular or diffuse large B-cell NHL who have not responded or progressed after 1 or 2 prior therapies; or subjects with CD20 and CD22-positive intermediate/aggressive NHL (diffuse large B-cell, mantle cell, transformed follicular or follicular grade 3b NHL) who have not responded or progressed after 1 or more prior therapies and are refractory to a previous rituximab containing therapy.
- Prior therapy must contain at least one course of rituximab therapy, as single agent or in combination.
- Measurable disease.
Exclusion Criteria
- Subjects who are candidates for other potentially curative therapies.
- Subjects must not have received previous radioimmunotherapy.
- Subjects who have undergone a prior bone marrow transplantation within the last 6 months.
Data sourced from ClinicalTrials.gov (NCT00299494). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.