Trial Outcomes & Findings for Study Evaluating Inotuzumab Ozogamicin [CMC-544] Administered In Combination With Rituximab In Subjects With Non-Hodgkin's Lymphoma (NHL) (NCT NCT00299494)

A Open-Label, Phase 1/2 Study of CMC-544 (Inotuzumab Ozogamicin) in Combination With Rituximab in Subjects

Eligible Subjects were Randomly Assigned to Study Treatments

Study Evaluating Inotuzumab Ozogamicin [CMC-544] Administered In Combination With Rituximab In Subjects With Non-Hodgkin's Lymphoma (NHL)

Inotuzumab ozogamicin was dose escalated (3 to 6 evaluable participants enrolled per dose cohort) during the first 28 days after the first administration of inotuzumab ozogamicin + rituximab. Enrollment at the next dose level or enrollment of additional subjects into a cohort proceeded according to the following criteria: 0 dose-limiting toxicity (DLT) by Day 28 of first dose move to higher dose, 1 participant reporting DLT but no others in cohort by Day 28 of first dose move to higher dose, greater than 2 participants reporting DLT by Day 28 of first dose stop and prior dose level considered MTD. The worldwide medical monitor and investigators reviewed all significant study drug-related toxicities to determine if the dose escalation rules were satisfied and whether the dose escalation schedule required modification.

A TEAE is any event that occurred after the first dose of study drug up to 56 days post the last dose of study drug (either rituximab or inotuzumab ozogamicin).

CR: a. Complete disappearance of all detectable clinical and radiographic evidence of disease, disease-related symptoms, and normalization of NHL assignable biochemical abnormalities ; b. lymph nodes and nodal masses must have regressed to normal size; c. Spleen regressed in size and not palpable on physical exam, size of other organs enlarged due to disease decreased in size; d. Repeat bone marrow infiltrate clear. CRu: CR but allows for a. Residual lymph node mass \>1.5 cm in greatest transverse diameter has regressed by more than 75% in diameter. Individual nodes that were previously confluent regressed more than 75 % in their product diameters; b. Indeterminate bone marrow. PR: a. ≥50 % decrease in product of the diameters (SPD) of the 6 largest dominant nodes or nodal masses; b. No increase in size of other nodes, liver, or spleen, c. Liver or spleen nodules regressed ≥50% in the SPD; d. Other organs usually assessable, no measurable disease present.

The Kaplan-Meier method was used to determine PFS. 95% 2-sided confidence interval were calculated using stratified Cox proportional hazard regression. Relapsed or Progressive Disease (PD) requires the following: a. Appearance of any new lesions, b. Increase by \>= 50% in the size of previously involved sites, c. \>= 50% increase in greatest diameter of any previously identified node greater than 1 cm in its short axis or in the SPD of more than one node, d. \>= 50% increase from nadir in the product diameter of any previously identified abnormal node for PRs or nonresponders, e. Enlarging spleen or liver.

Progression Free Survival is defined as the time interval from the first dose of test article until the first date on which relapsed disease, progression, initiation of new anti-cancer treatment due to persistent/refractory disease, or death was documented, censored at the last tumor evaluation.

OS was defined as the time from randomization to death due to any cause, censoring at the date of last contact. The Kaplan-Meier method was used to determine OS. 95% 2-sided confidence interval were calculated using stratified Cox proportional hazard regression.

Overall Survival (OS) was defined as the time from randomization to death due to any cause, censoring at the date of last contact. The Kaplan-Meier method was used to determine OS. 95% 2-sided confidence interval were calculated using stratified Cox proportional hazard regression.

TTP is defined as the interval from the first dose of the test article until the first date on which relapsed disease or progression, or death secondary to progression is documented, censored at the last disease assessment. Relapsed or Progressive Disease (PD) requires the following: a. Appearance of any new lesions, b. Increase by \>= 50% in the size of previously involved sites, c. \>= 50% increase in greatest diameter of any previously identified node greater than 1 cm in its short axis or in the SPD of more than one node, d. \>= 50% increase from nadir in the product diameter of any previously identified abnormal node for PRs or nonresponders, e. Enlarging spleen or liver. The Kaplan-Meier method was used to determine TTP. 95% 2-sided confidence interval were calculated using stratified Cox proportional hazard regression.

Time-to-Tumor Progression (TTP): is defined as the interval from the first dose of the test article until the first date on which relapsed disease or progression, or death secondary to progression is documented, censored at the last disease assessment. Relapsed or Progressive Disease (PD) requires the following: a. Appearance of any new lesions, b. Increase by \>=50% in the size of previously involved sites, c. \>= 50% increase in greatest diameter of any previously identified node greater than 1 cm in its short axis or in the SPD of more than one node, d. \>= 50% increase from nadir in the product diameter of any previously identified abnormal node for PRs or nonresponders, e. Enlarging spleen or liver. The Kaplan-Meier method was used to determineTTP. 95% 2-sided confidence interval were calculated using stratified Cox proportional hazard regression.

Time from date measurement criteria met for CR, CRu, or PR (whichever occurred first) until first date relapsed disease/date of death. CR: Complete disappearance of all detectable clinical, radiographic evidence of disease, disease-related symptoms, normalization of NHL assignable biochemical abnormalities; lymph nodes, nodal masses regressed to normal size; spleen size regressed, not palpable on physical exam, size of other organs enlarged due to disease. CRu: CR but allows for: residual lymph node mass \>1.5 cm in greatest transverse diameter that regressed \>75% in product diameter. Individual nodes previously confluent, regressed by \>75% in their product diameters; Indeterminate bone marrow. PR: ≥50% decrease in SPD of 6 largest dominant nodes/nodal masses; No increase in size of other nodes, liver, or spleen; Splenic/hepatic nodules regressed by ≥50% in SPD; Except splenic/hepatic nodules, involvement of other organs assessable and no measurable disease present.

Serum concentration of inotuzumab ozogamicin on Dosing Days 30 and 58 were measured. AUCinf of inotuzumab ozogamicin was reported. AUCinf: AUClast (area under the serum concentration-time profile for inotuzumab ozogamicin from time zero to the time of the last quantifiable concentration) +(Clast \[last quantifiable concentration\]/kel \[elimination rate constant\]) where Clast is the predicted serum concentration of inotuzumab ozogamicin at the last quantifiable timepoint estimated from the log-linear regression analysis. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

Serum concentration of inotuzumab ozogamicin on Dosing Days 1, 30 and 58 were measured. AUC of inotuzumab ozogamicin was reported. AUClast is area under the serum concentration-time profile from time zero to the time of the Clast, using Linear/Log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.

Tlast of inotuzumab ozogamicin on Dosing Days 1, 30, and 58 was reported. Tlast: Time of last quantifiable concentration of inotuzumab ozogamicin. Observed directly from data. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.

Steady-state serum concentrations of inotuzumab ozogamicin on Dosing Days 1, 30 and 58 were measured. AUCtau of inotuzumab ozogamicin was reported. AUCtau=AUC over dosage interval tau calculated using Linear/log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.

Serum concentration of inotuzumab ozogamicin on Dosing Days 1, 30, and 58 were measured. Cmax of inotuzumab ozogamicin was reported. Cmax was observed directly from data. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.

Tmax: Time at which Cmax occurs. Observed directly from data as time of first occurrence. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.

Cav: AUCtau (Area under the concentration time profile)/tau for Dosing Day 30 Cycle 2 and Dosing Day 58 Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

Cmin: Lowest concentration observed during the dosing interval tau. Observed directly from data from Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

Clearance is defined as Dose/AUCinf. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

Vss of inotuzumab ozogamicin on Dosing Days 30 and 58 were reported. Vss=CL\*MRT (mean residence time). Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

MRT: AUMCinf/AUCinf - DOF (degrees of freedom)/2, where AUMCinf is the area under the first moment curve derived using the linear/log trapezoidal method, and DOF is the duration of the IV infusion dose. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

Termnial half-life (t½): Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

AUCinf: AUClast+(Clast/kel) where Clast is the predicted serum concentration at the last quantifiable timepoint estimated from the log-linear regression analysis. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

AUClast: AUC over dosage interval through last measurable time point, Tlast, using Linear/Log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.

Tlast: Time of last quantifiable concentration. Observed directly from data. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.

AUCtau=AUC over dosage interval tau calculated using Linear/log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.

Cmax: Observed directly from data Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.

Tmax: Time at which Cmax occurs. Observed directly from data as time of first occurrence. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.

Cav: AUCtau/tau for Dosing Day 30 Cycle 2 and Dosing Day 58 Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

Cmin: Lowest concentration observed during the dosing interval tau. Observed directly from data from Day 30 for Cycle 2; and Day 58 for Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

Clearance defined as Dose/AUCinf. Corresponds to Dosing Day 30 for Cycle 2 and dosing Day 58 for Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

Vss: Steady-state volume of distribution CL\*MRT of inotuzumab ozogamicin Day 30 for Cycle 2; and Day 58 for Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

MRT: AUMCinf/AUCinf - DOF/2, where AUMCinf is the area under the first moment curve derived using the linear/log trapezoidal method, and DOF is the duration of the IV infusion dose. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

Termnial half-life (t½): Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

AUClast: AUC over dosage interval through last measurable time point, Tlast, using Linear/Log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.

Tlast: Time of last quantifiable concentration. Observed directly from data. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.

Cmax: Observed directly from data Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.

Tmax: Time at which Cmax occurs. Observed directly from data as time of first occurrence. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.

Cmin: Lowest concentration observed during the dosing interval tau. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

AUCinf: AUClast+(Clast/kel) where Clast is the predicted serum concentration at the last quantifiable timepoint estimated from the log-linear regression analysis. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

AUClast: AUC over dosage interval through last measurable time point, Tlast, using Linear/Log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.

Tlast: Time of last quantifiable concentration. Observed directly from data. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.

Termnial half-life (t½): Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

AUCtau=AUC over dosage interval tau calculated using Linear/log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.

Cmax: Observed directly from data Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.

Tmax: Time at which Cmax occurs. Observed directly from data as time of first occurrence. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.

Cav: AUCtau/tau for Dosing Day 30 Cycle 2 and Dosing Day 58 Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

Cmin: Lowest concentration observed during the dosing interval tau. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

Clearance defined as Dose/AUCinf. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

Vss: Steady-state volume of distribution CL\*MRT of inotuzumab ozogamicin Day 30 for Cycle 2; and Day 58 for Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.