Study Evaluating CMC-544 In B-Cell Non-Hodgkin's Lymphoma

Study Overview
=================
Brief Summary
-----------------
To determine the Maximum Tolerated Dose (MTD), the tolerability, and the initial safety profile of CMC-544 in subjects with B-cell Non-Hodgkin's Lymphoma (NHL).

Official Title
-----------------
A Phase 1 Study Of Cmc-544 Administered As A Single Agent In Subjects With B-cell Non- Hodgkin's Lymphoma

Conditions
-----------------
Lymphoma, B-Cell

Intervention / Treatment
-----------------
* Drug: Inotuzumab ozogamicin [CMC-544]


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects who have been previously diagnosed with CD22-positive, B-cell NHL, according to WHO classification, which has progressed after at least 2 prior therapies of probable clinical benefit At the expanded cohort, part 2 of the study, subjects must have one of the following: Follicular lymphoma previously treated with at least one dose of rituximab, but have not received radioimmunotherapy Diffuse large B-cell lymphoma Age 18 years or older Exclusion Criteria: Candidate for potentially curative therapies in the opinion of the investigator Chronic lymphocytic leukemia Burkitt's lymphoma, primary effusion lymphoma, and precursor B-cell lymphoblastic lymphoma

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inotuzumab ozogamicin<br>Inotuzumab ozogamicin, iv, dose escalation and expanded cohort at 1.8mg/m2 | Drug: Inotuzumab ozogamicin [CMC-544]<br>* CMC-544, IV, dose escalation trial<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent adverse events (TEAE) are defined as any new event reported after first dose of study drug up to 42 days after last dose of study drug, or any event that is worse in severity than at any time during the baseline period. AEs included both SAEs and non-serious adverse events (non-SAEs). | Baseline up to 42 days after last dose of study drug (up to Day 225) | 
| Number of Participants With Grade 3 or Higher Grades Treatment-Emergent Adverse Events (TEAEs) Based on Severity | AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AE severity was defined to be the maximum toxicity grade of the treatment-emergent adverse events (TEAEs) experienced by the participants during the study. AE was assessed according to severity; Grade 1 (mild AE), Grade 2 (moderate AE), Grade 3 (severe AE), Grade 4 (life-threatening or disabling AE), Grade 5 (death related to AE). Participants with Grade 3 or higher grades TEAEs were reported. | Baseline up to 42 days after last dose of study drug (up to Day 225) | 
| Maximum Tolerated Dose (MTD): Part 1 (Dose Escalation Cohorts) | MTD was defined as highest dose level for which no more than 1 participant in a dose cohort experienced dose limiting toxicity (DLT). DLT was defined as any of the following events occurring during the first 21 days (or 28 days for participants treated every 4 weeks) days of study medication and considered at least possibly-related to study medication: any grade 3 or 4 non-hematologic toxicity except grade 3 alopecia, nausea, or vomiting, any grade 4 febrile neutropenia, any grade 4 thrombocytopenia or any bleeding episode requiring platelet transfusion, any grade 4 absolute neutrophil count (for a duration of greater than or equal to [>=] 7 days), delayed recovery (less than or equal to [<=] grade 1 or baseline) from a toxicity that delays the initiation of the next dose by more than 2 weeks. | Baseline up to Day 28 | 
| Number of Participants With Dose-limiting Toxicity (DLT) | DLT was classified as per National Cancer Institute common terminology criteria for adverse events (NCI CTCAE) version 3.0 and defined as any of the following events occurring during the first 21 days (or 28 days for participants treated every 4 weeks) days of study medication and considered at least possibly-related to study medication: any grade 3 or 4 non-hematologic toxicity except grade 3 alopecia, nausea, or vomiting, any grade 4 febrile neutropenia, any grade 4 thrombocytopenia or any bleeding episode requiring platelet transfusion, any grade 4 absolute neutrophil count (for a duration of greater than or equal to [>=] 7 days), delayed recovery (less than or equal to [<=] grade 1 or baseline) from a toxicity that delays the initiation of the next dose by more than 14 days. | Baseline up to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS): Evaluable Population- Part 2 (Lead-in + Expanded Cohorts) | PFS was based on Kaplan-Meier estimates. PFS was defined as the time interval from the first dose of study medication until the first date on which relapsed disease, or progression (as per the International Response Criteria for Non-Hodgkin Lymphoma) or death, was documented, censored at the last tumor evaluation date. This outcome measure was analyzed in participants with follicular lymphoma or diffuse large B-cell lymphoma. | Baseline, every 8 weeks up to Year 1, then every 12 weeks up to Year 2, and then every 6 months until tumor progression or death (up to Year 5) | 
| Progression-Free Survival (PFS): Intent-to-treat Population-Part 2 (Lead-in + Expanded Cohorts) | PFS was based on Kaplan-Meier estimates. PFS was defined as the time interval from the first dose of study medication until the first date on which relapsed disease, or progression (as per International Response Criteria for Non-Hodgkin Lymphoma) or death, was documented, censored at the last tumor evaluation date. This outcome measure was analyzed in participants with follicular lymphoma or diffuse large B-cell lymphoma. | Baseline, every 8 weeks up to Year 1, then every 12 weeks up to Year 2, and then every 6 months until tumor progression or death (up to Year 5) | 
| Overall Survival (OS): Evaluable Population- Part 2 (Lead-in + Expanded Cohorts) | OS was based on Kaplan-Meier method. Survival was defined as the time period from the first dose of study drug until the date of death, censored at the participant's last contact date. This outcome measure was analyzed in participants with follicular lymphoma or diffuse large B-cell lymphoma. | Baseline up to Year 5 | 
| Overall Survival (OS): Intent-to-treat Population: Part 2 (Lead-in + Expanded Cohorts) | Interval OS was based on Kaplan-Meier method. Survival was defined as the time period from the first dose of study drug until the date of death, censored at the participant's last contact date. This outcome measure was analyzed in participants with follicular lymphoma or diffuse large B-cell lymphoma. | Baseline up to Year 5 | 
| Number of Participants With Best Overall Response (BOR): Part 2 (Expanded Cohorts) | Participants with BOR=with complete response(CR),unconfirmed CR(CRu) or partial response (PR) as per International Response Criteria for NHL. CR: Total disappearance of all detectable clinical,radiographic sign of disease/related symptoms,normalization biochemical abnormalities related to NHL;if enlarged before therapy all lymph nodes,nodal masses,other organs regressed to normal size and spleen regressed in size,undetectable on physical exam,clear bone marrow infiltrate. CRu: CR but allows for residual lymph node mass >1.5 cm in greatest transverse diameter and all individual nodes previously merged were regressed by >75% in product diameters and indeterminate bone marrow. PR:>=50% decrease in sum of products of greatest diameters(SPD) of 6 largest dominant nodes/nodal masses,no increase in size of other nodes/spleen/liver, 50% decrease in SPD of splenic,hepatic nodules,involvement of other organs considered assessable,not measurable disease with exception of splenic,hepatic nodules. | Baseline, every 8 weeks up to Year 1, then every 12 weeks up to Year 2, and then every 6 months until tumor progression or death (up to Year 5) | 
| Duration of Overall Response (DoR): Part 2 (Lead-in + Expanded Cohorts) | Duration of overall response was defined as the time from the date that measurement criteria were met for CR, CRu, or PR (whichever status was recorded first) until the first date that relapsed disease was objectively documented as per International Response Criteria for NHL, taking as reference for relapsed disease the smallest measurements recorded since the treatment started. This outcome measure was analyzed in participants with follicular lymphoma or diffuse large B-cell lymphoma. | Baseline, every 8 weeks up to Year 1, then every 12 weeks up to Year 2, and then every 6 months until tumor progression or death (up to Year 5) | 
| Time-to-Tumor Progression: Part 2 (Expanded Cohorts) | Time to tumor progression was defined as the interval from the start of the treatment until the first date on which relapsed disease or progression is documented, censored at the last disease assessment. This outcome measure was analyzed in participants with follicular lymphoma or diffuse large B-cell lymphoma. | Baseline, every 8 weeks up to Year 1, then every 12 weeks up to Year 2, and then every 6 months until tumor progression or death (up to Year 5) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
B-Cell, Non-Hodgkin's, Lymphoma