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

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ClinicalTrials.gov Identifier: NCT00073749
Recruitment Status : Completed
First Posted : December 5, 2003
Results First Posted : October 26, 2018
Last Update Posted : December 17, 2018
Sponsor:
Information provided by (Responsible Party):
Pfizer

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).

Condition or disease Intervention/treatment Phase
Lymphoma, B-Cell Drug: Inotuzumab ozogamicin [CMC-544] Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 79 participants
Allocation: Non-Randomized
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study Of Cmc-544 Administered As A Single Agent In Subjects With B-cell Non- Hodgkin's Lymphoma
Actual Study Start Date : August 2003
Actual Primary Completion Date : December 2010
Actual Study Completion Date : December 2010

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: Inotuzumab ozogamicin
Inotuzumab ozogamicin, iv, dose escalation and expanded cohort at 1.8mg/m2
Drug: Inotuzumab ozogamicin [CMC-544]
CMC-544, IV, dose escalation trial




Primary Outcome Measures :
  1. Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 42 days after last dose of study drug (up to Day 225) ]
    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).

  2. Number of Participants With Grade 3 or Higher Grades Treatment-Emergent Adverse Events (TEAEs) Based on Severity [ Time Frame: Baseline up to 42 days after last dose of study drug (up to Day 225) ]
    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.

  3. Maximum Tolerated Dose (MTD): Part 1 (Dose Escalation Cohorts) [ Time Frame: Baseline up to Day 28 ]
    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.

  4. Number of Participants With Dose-limiting Toxicity (DLT) [ Time Frame: Baseline up to Day 28 ]
    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.


Secondary Outcome Measures :
  1. Progression-Free Survival (PFS): Evaluable Population- Part 2 (Lead-in + Expanded Cohorts) [ Time Frame: 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) ]
    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.

  2. Progression-Free Survival (PFS): Intent-to-treat Population-Part 2 (Lead-in + Expanded Cohorts) [ Time Frame: 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) ]
    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.

  3. Overall Survival (OS): Evaluable Population- Part 2 (Lead-in + Expanded Cohorts) [ Time Frame: Baseline up to Year 5 ]
    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.

  4. Overall Survival (OS): Intent-to-treat Population: Part 2 (Lead-in + Expanded Cohorts) [ Time Frame: Baseline up to Year 5 ]
    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.

  5. Number of Participants With Best Overall Response (BOR): Part 2 (Expanded Cohorts) [ Time Frame: 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) ]
    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.

  6. Duration of Overall Response (DoR): Part 2 (Lead-in + Expanded Cohorts) [ Time Frame: 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 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.

  7. Time-to-Tumor Progression: Part 2 (Expanded Cohorts) [ Time Frame: 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 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.


Other Outcome Measures:
  1. Percentage of Participants With Objective Response- Evaluable Population: Part 2 (Lead-in + Expanded Cohorts) [ Time Frame: Baseline up to 42 days after last dose (Day 225) ]
    Participants (having follicular or diffuse lymphoma) with objective response based assessment of CR, CRu or 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 SPD of 6 largest dominant nodes or nodal masses, no increase in size of other nodes, spleen or liver, 50% decrease in SPD of splenic, hepatic nodules, involvement of other organs considered assessable, not measurable disease with exception of splenic, hepatic nodules.

  2. Percentage of Participants With Objective Response- Intent-to-treat Population: Part 2 (Lead in+ Expanded Cohorts) [ Time Frame: Baseline up to 42 days after last dose of study drug (Day 225) ]
    Participants (having follicular or diffuse lymphoma) with objective response based assessment of CR, CRu or 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 SPD of 6 largest dominant nodes or nodal masses, no increase in size of other nodes, spleen or liver, 50% decrease in SPD of splenic, hepatic nodules, involvement of other organs considered assessable, not measurable disease with exception of splenic, hepatic nodules.



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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00073749


Locations
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United States, Alabama
UAB CCC Clinical Studies Unit
Birmingham, Alabama, United States, 35233
University of Alabama at Birmingham Kirklin Clinic
Birmingham, Alabama, United States, 35233
UAB Russell Ambulatory Pharmacy
Birmingham, Alabama, United States, 35294
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, Illinois
Northwestern Medical Faculty Foundation
Chicago, Illinois, United States, 60611
Northwestern Memorial Hospital
Chicago, Illinois, United States, 60611
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
United States, Ohio
The Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
United States, Texas
M.D. Anderson Cancer Center
Houston, Texas, United States, 77030-4009
Belgium
Universitair Ziekenhuis Gasthuisberg
Leuven, Belgium, 3000
France
Hopital Saint Louis
Paris, France, 75010
Centre Hospitalier Lyon-Sud
Pierre Benite Cedex, France, 69495
Germany
Universitätsklinikum Bonn
Bonn, NRW, Germany, 53105
Universitaetsmedizin der Johannes Gutenberg-Universitaet
Mainz, Germany, 55131
Medizinische Klinik und Poliklinik III, Klinikum der Universitat Muenchen-Grosshadern
Muenchen, Germany, 81377
Universitaet Muenchen Klinikum Grosshadern
Muenchen, Germany, 81377
Spain
Hospital de la Santa Creu I Sant Pau
Barcelona, Spain, 08025
Hospital Clinic I Provincial
Barcelona, Spain, 08036
Switzerland
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland, 1011
United Kingdom
St Bartholomew's Hospital
London, United Kingdom, EC1A 7BE
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00073749     History of Changes
Other Study ID Numbers: 3129K1-100
B1931002 ( Other Identifier: Alias Study Number )
First Posted: December 5, 2003    Key Record Dates
Results First Posted: October 26, 2018
Last Update Posted: December 17, 2018
Last Verified: December 2018
Keywords provided by Pfizer:
B-Cell
Non-Hodgkin's
Lymphoma
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Inotuzumab Ozogamicin
Antineoplastic Agents