BRP: IIT CTI Bendamustine, Rituximab, Pixantrone in Relapsed/Refractory B Cell Non-Hodgkin's Lymphoma
Study Details
Study Description
Brief Summary
This is a phase I trial of the combination of bendamustine, rituximab and pixantrone in patients with relapsed/refractory B cell non-Hodgkin lymphoma. A standard 3+3 design will be used to determine the maximum tolerated dose (MTD) of the combination. A static dose of bendamustine and rituximab will be used and the dose of pixantrone will be escalated in each cohort. Pixantrone will be dosed on a 21 day cycle at 55mg/m2, 85mg/m2, and 115mg/m2 in sequential cohorts dependent on acceptable toxicity profile at each dose level. MTD will be determined based on DLTs that occur during the first 2 cycles of the drug combination.
Phase II did not proceed as planned due to withdrawal of pixantrone from the US.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 1 |
Detailed Description
This is a phase I trial utilizing a traditional 3+3 design to evaluate maximum tolerated dose (MTD) and optimal dose schedule of pixantrone in combination with bendamustine (120mg/m2 on day 1 of each 21 day cycle) and rituximab (375mg/m2 on day 1 of each 21 day cycle). No patients will be entered on an escalated dosage level until at least 3 patients have been treated at the previous level and assessed for a dose limiting toxicity. Dose levels will be escalated in cohorts of 3 patients as long as no drug-related DLT occurs in the first 2 cycles. If one patient is observed to suffer a DLT, this cohort will be expanded to include at least 6 patients total. If less than 2 patients in the expanded cohort of 6 patients experience a DLT, dose escalation will resume. If 2 of 6 patients enrolled at the same dose level experience a DLT, the MTD has been exceeded, and the dose escalation will cease. The next lower dose will be considered the MTD. If any patient withdraws from the study prior to completing 2 cycles for reasons other than a DLT then that patient will be replaced in order to determine the MTD.
If dose limiting toxicity is observed at the initial dose level in 2 patients, the MTD has been exceeded and the starting dose level will be reduced to 25mg/m2. If 1 patient experiences a DLT in the -1 dose range, the cohort will be expanded to at least 6 patients. If a second patient experiences a DLT at the -1 dose level, the trial will be closed.
For part 1, those who have a confirmed diagnosis of relapsed/refractory B cell non-Hodgkin's lymphoma of any subtype will be considered eligible for enrollment. Each cycle will be 21 days. Subjects will be assessed for DLTs during the first 2 cycles of study drug. They will be assessed for response after cycle 2. Patients not experiencing a DLT during the first 2 cycles and who have stable disease or better may continue to receive up to 6 cycles of treatment with the triplet combination. If any patient withdraws from the study prior to completing 2 cycles for reasons other than a DLT then that patient will be replaced in order to determine the MTD.
Phase II did not proceed as planned due to withdrawal of pixantrone from the US.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Phase 1: Pixantrone, 55mg/m^2 Bendamustine, 120mg/m2; administered first on Day 1 of each cycle. Rituximab, 375mg/m2; administered second on Day 1 of each cycle. Pixantrone, 55mg/m2; to be administered last, 4-6 hours after bendamustine, on Day 1 of each cycle Pegfilgrastim, 6mg; administered on Day 2 of each cycle |
Drug: Bendamustine + Rituximab + Pixantrone
Dose escalation of pixantrone (55mg/m2, 85mg/m2 and 115mg/m2) in combination with static dose bendamustine (120mg/m2 on Day 1 of each 21 day) and rituximab (375mg/m2 on Day 1 of each 21 day cycle).
Other Names:
Drug: Pegfilgrastim
6mg administered on Day 2 of each 21 day cycle
|
Experimental: Phase 1: Pixantrone, 85mg/m^2 Bendamustine, 120mg/m2; administered first on Day 1 of each cycle. Rituximab, 375mg/m2; administered second on Day 1 of each cycle. Pixantrone, 85mg/m2; to be administered last, 4-6 hours after bendamustine, on Day 1 of each cycle Pegfilgrastim, 6mg; administered on Day 2 of each cycle |
Drug: Bendamustine + Rituximab + Pixantrone
Dose escalation of pixantrone (55mg/m2, 85mg/m2 and 115mg/m2) in combination with static dose bendamustine (120mg/m2 on Day 1 of each 21 day) and rituximab (375mg/m2 on Day 1 of each 21 day cycle).
Other Names:
Drug: Pegfilgrastim
6mg administered on Day 2 of each 21 day cycle
|
Experimental: Phase 1: Pixantrone, 115mg/m^2 Bendamustine, 120mg/m2; administered first on Day 1 of each cycle. Rituximab, 375mg/m2; administered second on Day 1 of each cycle. Pixantrone, 115mg/m2; to be administered last, 4-6 hours after bendamustine, on Day 1 of each cycle Pegfilgrastim, 6mg; administered on Day 2 of each cycle |
Drug: Bendamustine + Rituximab + Pixantrone
Dose escalation of pixantrone (55mg/m2, 85mg/m2 and 115mg/m2) in combination with static dose bendamustine (120mg/m2 on Day 1 of each 21 day) and rituximab (375mg/m2 on Day 1 of each 21 day cycle).
Other Names:
Drug: Pegfilgrastim
6mg administered on Day 2 of each 21 day cycle
|
Outcome Measures
Primary Outcome Measures
- Maximum Tolerated Dose [4 years]
Dose-limiting toxicity (DLT) assessments were performed weekly during cycles 1 and 2. A DLT was defined as any grade 3 non-hematologic toxicity that lasted longer than 48 hours, despite proper supportive care, any grade 4 non-hematologic toxicity, or any grade 3 or 4 hematologic toxicity lasting longer than 7 days. Alopecia and febrile neutropenia were not considered DLTs. Any NCI CTC (National Cancer Institute Common Terminology Criteria) v4.03 grade 5 (death) toxicity was considered a DLT. Dose Limiting Toxicities were used as the assessment criteria to determine the Maximum Tolerated Dose (MTD). MTD is presented.
Secondary Outcome Measures
- Overall Response [up to 220 days]
Partial response and complete response evaluated using a modified version of the revised response criteria for malignant lymphoma by Cheson et al Complete Response (CR) • Complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present prior to therapy. Complete Response Unconfirmed (CRu) meets the CR criteria, but with one or more of the following: A residual node > 1.5 cm in greatest transverse diameter that has regressed >75% in the sum of the product of the diameters (SPD). Individual nodes that were previously confluent must have regressed >75% in their SPD compared with the size of the original mass. Indeterminate bone marrow (increased number or size of aggregates without cytologic or architectural atypia by immunohistochemistry or flow cytometry). Partial Response (PR) • A decrease of ≥ 50% in the SPD of up to six of the largest dominant nodes or nodal masses.
- Progression Free Survival [From day 1 of treatment to disease progression, death or 5 years, whichever comes first]
- Toxicity [30 days post last dose of study drug]
Dose limiting toxicities plus % of patients with a clinically significant change in left ventricular ejection fraction.
- Overall Survival [from day 1 of treatment to death]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Part I: Subjects must have relapsed or refractory B cell NHL;
-
Part II: Subjects must have relapsed or refractory aggressive B cell NHL including follicular lymphoma (FL) grade 3, Diffuse Large B Cell Lymphoma (DLBCL), transformed NHL, mantle cell lymphoma (MCL), or other aggressive B cell NHL histology as per the WHO 2008 criteria;
-
Refractory disease (defined as persistence of evaluable disease after therapy) or relapsed disease following at least one prior treatment regimen that should include autologous stem cell transplant unless a patient was not eligible or refused prior transplant;
-
Age ≥ 18 years old;
-
Eastern Cooperative Oncology Group (ECOG) performance status of ≤2;
-
Subjects must have measurable or evaluable disease based on physical exam and/or radiographs (CT, MRI, PET) or bone marrow involvement;
-
Female subject is either post-menopausal or surgically sterilized;
-
Laboratory Values:
-
Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L; lower levels accepted if due to marrow involvement by lymphoma
-
Platelets ≥ 75,000/mcl; lower levels accepted if due to marrow involvement by lymphoma
-
Total bilirubin ≤ 1.5 X institutional upper limit of normal; ≤ 3.0 ULN accepted in subjects with Gilbert's Syndrome
-
AST/ALT ≤ 1.5 X institutional upper limit of normal. Subjects with known liver involvement by lymphoma: AST/ALT ≤ 2 X institutional upper limit of normal
-
Serum creatinine < 1.5 X institutional upper limit of normal
- Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
Exclusion Criteria:
-
No chemotherapy, radiation, biologics or immunotherapy within 2 weeks prior to registration (6 weeks if last received BCNU or mitomycin C).
-
No radioimmunotherapy within 2 months prior to registration.
-
Subjects receiving chronic, systemic treatment with corticosteroids equivalent to > 20mg of prednisone per day. Subjects receiving replacement for adrenal insufficiency will be allowed on the study. Topical or inhaled corticosteroids are allowed.
-
Subjects with a history of another primary malignancy ≤ 3 years ago, with the exception of inactive basal, squamous cell carcinoma of the skin or superficial melanoma only requiring excision, prostate cancer with a PSA that has not increased for at least 3 months, carcinoma in situ of the cervix.
-
Major surgery ≤ 4 weeks prior to registration. Minor surgery ≤ 2 weeks prior to registration. Insertion of a vascular access device is not considered major or minor surgery. Subjects must have recovered from all surgery related toxicities to ≤ grade 1 or to baseline if subject started with > grade 1 toxicity, not otherwise violating the above inclusion criteria.
-
Subjects who have received investigational drugs ≤ 4 weeks prior to registration.
-
Impaired Cardiac Function:
-
QTc > 480 on screening ECG.
-
Previous history of angina pectoris or acute MI within 6 months
-
Congestive heart failure (New York Heart Association functional classification III-IV) or baseline MUGA/ECHO shows estimated LVEF < 45%
-
Any history of torsade de pointes, ventricular fibrillation, uncontrolled ventricular tachycardia, or uncontrolled atrial fibrillation.
-
Female patients who are pregnant or breastfeeding
-
Patients with history of untreated hepatitis B or who are known carriers of hepatitis B will be excluded from this trial. All subjects will be screened prior to study entry.
-
Concurrent use of other anti-cancer agents or anti-cancer treatments.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Duke University Medical Center | Durham | North Carolina | United States | 27705 |
Sponsors and Collaborators
- Anne Beaven, MD
- CTI BioPharma
Investigators
- Principal Investigator: David Rizzieri, MD, Duke University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Pro00030834
Study Results
Participant Flow
Recruitment Details | The study opened November 1, 2011 and closed to accrual September 22, 2016. Subjects were recruited through the Hematology Clinic at Duke University Medical Center. |
---|---|
Pre-assignment Detail |
Arm/Group Title | Bendamustine + Rituximab + Pixantrone |
---|---|
Arm/Group Description | Bendamustine, 120mg/m2; administered first on Day 1 of each cycle. Rituximab, 375mg/m2; administered second on Day 1 of each cycle. Pixantrone, variable dosing depending on the cohort and MTD (maximum tolerated dose); to be administered last, 4-6 hours after bendamustine, on Day 1 of each cycle Pegfilgrastim, 6mg; administered on Day 2 of each cycle Bendamustine + Rituximab + Pixantrone: Dose escalation of pixantrone (55mg/m2, 85mg/m2 and 115mg/m2) in combination with static dose bendamustine (120mg/m2 on Day 1 of each 21 day) and rituximab (375mg/m2 on Day 1 of each 21 day cycle). |
Period Title: Overall Study | |
STARTED | 33 |
COMPLETED | 22 |
NOT COMPLETED | 11 |
Baseline Characteristics
Arm/Group Title | Bendamustine + Rituximab + Pixantrone |
---|---|
Arm/Group Description | Bendamustine, 120mg/m2; administered first on Day 1 of each cycle. Rituximab, 375mg/m2; administered second on Day 1 of each cycle. Pixantrone, variable dosing depending on the cohort and MTD; to be administered last, 4-6 hours after bendamustine, on Day 1 of each cycle Pegfilgrastim, 6mg; administered on Day 2 of each cycle Bendamustine + Rituximab + Pixantrone: Dose escalation of pixantrone (55mg/m2, 85mg/m2 and 115mg/m2) in combination with static dose bendamustine (120mg/m2 on Day 1 of each 21 day) and rituximab (375mg/m2 on Day 1 of each 21 day cycle). |
Overall Participants | 33 |
Age (Count of Participants) | |
<=18 years |
0
0%
|
Between 18 and 65 years |
19
57.6%
|
>=65 years |
14
42.4%
|
Sex: Female, Male (Count of Participants) | |
Female |
10
30.3%
|
Male |
23
69.7%
|
Ethnicity (NIH/OMB) (Count of Participants) | |
Hispanic or Latino |
0
0%
|
Not Hispanic or Latino |
33
100%
|
Unknown or Not Reported |
0
0%
|
Race (NIH/OMB) (Count of Participants) | |
American Indian or Alaska Native |
0
0%
|
Asian |
0
0%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
Black or African American |
2
6.1%
|
White |
31
93.9%
|
More than one race |
0
0%
|
Unknown or Not Reported |
0
0%
|
Region of Enrollment (Count of Participants) | |
United States |
33
100%
|
Outcome Measures
Title | Maximum Tolerated Dose |
---|---|
Description | Dose-limiting toxicity (DLT) assessments were performed weekly during cycles 1 and 2. A DLT was defined as any grade 3 non-hematologic toxicity that lasted longer than 48 hours, despite proper supportive care, any grade 4 non-hematologic toxicity, or any grade 3 or 4 hematologic toxicity lasting longer than 7 days. Alopecia and febrile neutropenia were not considered DLTs. Any NCI CTC (National Cancer Institute Common Terminology Criteria) v4.03 grade 5 (death) toxicity was considered a DLT. Dose Limiting Toxicities were used as the assessment criteria to determine the Maximum Tolerated Dose (MTD). MTD is presented. |
Time Frame | 4 years |
Outcome Measure Data
Analysis Population Description |
---|
Over the course of 4 years, dose escalation was performed in 3 cohorts. Cohort 1 (Phase 1: Pixantrone, 55mg/m^2) enrolled 7 people; Cohort 2 (Phase 1: Pixantrone, 85mg/m^2) enrolled 7 people; Cohort 3 (Phase 1: Pixantrone, 115 mg/m^2) enrolled 7 people. |
Arm/Group Title | Bendamustine + Rituximab + Pixantrone + Pegfilgrastim |
---|---|
Arm/Group Description | Bendamustine, 120mg/m2; administered first on Day 1 of each cycle. Rituximab, 375mg/m2; administered second on Day 1 of each cycle. Pixantrone, variable dosing depending on the cohort and MTD; to be administered last, 4-6 hours after bendamustine, on Day 1 of each cycle Pegfilgrastim, 6mg; administered on Day 2 of each cycle Bendamustine + Rituximab + Pixantrone: Dose escalation of pixantrone (55mg/m2, 85mg/m2 and 115mg/m2) in combination with static dose bendamustine (120mg/m2 on Day 1 of each 21 day) and rituximab (375mg/m2 on Day 1 of each 21 day cycle). |
Measure Participants | 21 |
Number [milligrams per meter squared] |
115
|
Title | Overall Response |
---|---|
Description | Partial response and complete response evaluated using a modified version of the revised response criteria for malignant lymphoma by Cheson et al Complete Response (CR) • Complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present prior to therapy. Complete Response Unconfirmed (CRu) meets the CR criteria, but with one or more of the following: A residual node > 1.5 cm in greatest transverse diameter that has regressed >75% in the sum of the product of the diameters (SPD). Individual nodes that were previously confluent must have regressed >75% in their SPD compared with the size of the original mass. Indeterminate bone marrow (increased number or size of aggregates without cytologic or architectural atypia by immunohistochemistry or flow cytometry). Partial Response (PR) • A decrease of ≥ 50% in the SPD of up to six of the largest dominant nodes or nodal masses. |
Time Frame | up to 220 days |
Outcome Measure Data
Analysis Population Description |
---|
Subjects who received at least 2 cycles of study drug were included. Data from the single patient enrolled in the phase 2 portion of the trial was included with the phase I pixantrone 115mg/m2 group because the phase 2 patient also received the 115mg/m2 dose and the combined data seems more meaningful than presenting data for 1 patient separately. |
Arm/Group Title | Pixantrone, 55mg/m^2 | Pixantrone, 85mg/m^2 | Pixantrone, 115mg/m^2 |
---|---|---|---|
Arm/Group Description | Bendamustine, 120mg/m2; administered first on Day 1 of each cycle. Rituximab, 375mg/m2; administered second on Day 1 of each cycle. Pixantrone, 55mg/m2; to be administered last, 4-6 hours after bendamustine, on Day 1 of each cycle Pegfilgrastim, 6mg; administered on Day 2 of each cycle Bendamustine + Rituximab + Pixantrone: Dose escalation of pixantrone (55mg/m2, 85mg/m2 and 115mg/m2) in combination with static dose bendamustine (120mg/m2 on Day 1 of each 21 day) and rituximab (375mg/m2 on Day 1 of each 21 day cycle). | Bendamustine, 120mg/m2; administered first on Day 1 of each cycle. Rituximab, 375mg/m2; administered second on Day 1 of each cycle. Pixantrone, 85mg/m2; to be administered last, 4-6 hours after bendamustine, on Day 1 of each cycle Pegfilgrastim, 6mg; administered on Day 2 of each cycle Bendamustine + Rituximab + Pixantrone: Dose escalation of pixantrone (55mg/m2, 85mg/m2 and 115mg/m2) in combination with static dose bendamustine (120mg/m2 on Day 1 of each 21 day) and rituximab (375mg/m2 on Day 1 of each 21 day cycle). | Bendamustine, 120mg/m2; administered first on Day 1 of each cycle. Rituximab, 375mg/m2; administered second on Day 1 of each cycle. Pixantrone, 115mg/m2; to be administered last, 4-6 hours after bendamustine, on Day 1 of each cycle Pegfilgrastim, 6mg; administered on Day 2 of each cycle Bendamustine + Rituximab + Pixantrone: Dose escalation of pixantrone (55mg/m2, 85mg/m2 and 115mg/m2) in combination with static dose bendamustine (120mg/m2 on Day 1 of each 21 day) and rituximab (375mg/m2 on Day 1 of each 21 day cycle). |
Measure Participants | 4 | 3 | 7 |
Count of Participants [Participants] |
2
6.1%
|
2
NaN
|
5
NaN
|
Title | Progression Free Survival |
---|---|
Description | |
Time Frame | From day 1 of treatment to disease progression, death or 5 years, whichever comes first |
Outcome Measure Data
Analysis Population Description |
---|
Groups combined to include all subjects who completed the study. This analysis was originally planned for Phase 2; there was no intent to compare dose levels in Phase 1 because there would be insufficient power to make meaningful comparisons. |
Arm/Group Title | Bendamustine + Rituximab + Pixantrone + Pegfilgrastim |
---|---|
Arm/Group Description | Bendamustine, 120mg/m2; administered first on Day 1 of each cycle. Rituximab, 375mg/m2; administered second on Day 1 of each cycle. Pixantrone, variable dosing depending on the cohort and MTD; to be administered last, 4-6 hours after bendamustine, on Day 1 of each cycle Pegfilgrastim, 6mg; administered on Day 2 of each cycle Bendamustine + Rituximab + Pixantrone: Dose escalation of pixantrone (55mg/m2, 85mg/m2 and 115mg/m2) in combination with static dose bendamustine (120mg/m2 on Day 1 of each 21 day) and rituximab (375mg/m2 on Day 1 of each 21 day cycle). |
Measure Participants | 22 |
Median (95% Confidence Interval) [months] |
3.9
|
Title | Toxicity |
---|---|
Description | Dose limiting toxicities plus % of patients with a clinically significant change in left ventricular ejection fraction. |
Time Frame | 30 days post last dose of study drug |
Outcome Measure Data
Analysis Population Description |
---|
Phase 1 subjects who received study drugs. |
Arm/Group Title | Phase 1: Pixantrone, 55mg/m^2 | Phase 1: Pixantrone, 85mg/m^2 | Phase 1: Pixantrone, 115mg/m^2 |
---|---|---|---|
Arm/Group Description | Bendamustine, 120mg/m2; administered first on Day 1 of each cycle. Rituximab, 375mg/m2; administered second on Day 1 of each cycle. Pixantrone, 55mg/m2; to be administered last, 4-6 hours after bendamustine, on Day 1 of each cycle Pegfilgrastim, 6mg; administered on Day 2 of each cycle Bendamustine + Rituximab + Pixantrone: Dose escalation of pixantrone (55mg/m2, 85mg/m2 and 115mg/m2) in combination with static dose bendamustine (120mg/m2 on Day 1 of each 21 day) and rituximab (375mg/m2 on Day 1 of each 21 day cycle). | Bendamustine, 120mg/m2; administered first on Day 1 of each cycle. Rituximab, 375mg/m2; administered second on Day 1 of each cycle. Pixantrone, 85mg/m2; to be administered last, 4-6 hours after bendamustine, on Day 1 of each cycle Pegfilgrastim, 6mg; administered on Day 2 of each cycle Bendamustine + Rituximab + Pixantrone: Dose escalation of pixantrone (55mg/m2, 85mg/m2 and 115mg/m2) in combination with static dose bendamustine (120mg/m2 on Day 1 of each 21 day) and rituximab (375mg/m2 on Day 1 of each 21 day cycle). | Bendamustine, 120mg/m2; administered first on Day 1 of each cycle. Rituximab, 375mg/m2; administered second on Day 1 of each cycle. Pixantrone, 115mg/m2; to be administered last, 4-6 hours after bendamustine, on Day 1 of each cycle Pegfilgrastim, 6mg; administered on Day 2 of each cycle Bendamustine + Rituximab + Pixantrone: Dose escalation of pixantrone (55mg/m2, 85mg/m2 and 115mg/m2) in combination with static dose bendamustine (120mg/m2 on Day 1 of each 21 day) and rituximab (375mg/m2 on Day 1 of each 21 day cycle). |
Measure Participants | 7 | 7 | 7 |
Dose-Limiting Toxicity |
1
3%
|
1
NaN
|
1
NaN
|
Left Ventricular Ejection Fraction |
1
3%
|
0
NaN
|
0
NaN
|
Other Adverse Events |
6
18.2%
|
6
NaN
|
6
NaN
|
Title | Overall Survival |
---|---|
Description | |
Time Frame | from day 1 of treatment to death |
Outcome Measure Data
Analysis Population Description |
---|
Groups combined to include all subjects who completed the study. This analysis was originally planned for Phase 2; there was no intent to compare dose levels in Phase 1 because there would be insufficient power to make meaningful comparisons. |
Arm/Group Title | Bendamustine + Rituximab + Pixantrone + Pegfilgrastim |
---|---|
Arm/Group Description | Bendamustine, 120mg/m2; administered first on Day 1 of each cycle. Rituximab, 375mg/m2; administered second on Day 1 of each cycle. Pixantrone, variable dosing depending on the cohort and MTD; to be administered last, 4-6 hours after bendamustine, on Day 1 of each cycle Pegfilgrastim, 6mg; administered on Day 2 of each cycle Bendamustine + Rituximab + Pixantrone: Dose escalation of pixantrone (55mg/m2, 85mg/m2 and 115mg/m2) in combination with static dose bendamustine (120mg/m2 on Day 1 of each 21 day) and rituximab (375mg/m2 on Day 1 of each 21 day cycle). |
Measure Participants | 22 |
Median (95% Confidence Interval) [months] |
7.9
|
Adverse Events
Time Frame | Up to 220 days | |||||
---|---|---|---|---|---|---|
Adverse Event Reporting Description | Subjects who received at least 2 cycles of study drug were included. Data from the single patient enrolled in the phase 2 portion of the trial was included with the phase I pixantrone 115mg/m2 group because the phase 2 patient also received the 115mg/m2 dose and the combined data seems more meaningful than presenting data for 1 patient separately. | |||||
Arm/Group Title | Pixantrone, 55mg/m^2 | Pixantrone, 85mg/m^2 | Pixantrone, 115mg/m^2 | |||
Arm/Group Description | Bendamustine, 120mg/m2; administered first on Day 1 of each cycle. Rituximab, 375mg/m2; administered second on Day 1 of each cycle. Pixantrone, 55mg/m2; to be administered last, 4-6 hours after bendamustine, on Day 1 of each cycle Pegfilgrastim, 6mg; administered on Day 2 of each cycle | Bendamustine, 120mg/m2; administered first on Day 1 of each cycle. Rituximab, 375mg/m2; administered second on Day 1 of each cycle. Pixantrone, 85mg/m2; to be administered last, 4-6 hours after bendamustine, on Day 1 of each cycle Pegfilgrastim, 6mg; administered on Day 2 of each cycle | Bendamustine, 120mg/m2; administered first on Day 1 of each cycle. Rituximab, 375mg/m2; administered second on Day 1 of each cycle. Pixantrone, 115mg/m2; to be administered last, 4-6 hours after bendamustine, on Day 1 of each cycle Pegfilgrastim, 6mg; administered on Day 2 of each cycle | |||
All Cause Mortality |
||||||
Pixantrone, 55mg/m^2 | Pixantrone, 85mg/m^2 | Pixantrone, 115mg/m^2 | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 6/7 (85.7%) | 7/7 (100%) | 8/8 (100%) | |||
Serious Adverse Events |
||||||
Pixantrone, 55mg/m^2 | Pixantrone, 85mg/m^2 | Pixantrone, 115mg/m^2 | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 3/7 (42.9%) | 0/7 (0%) | 2/8 (25%) | |||
Blood and lymphatic system disorders | ||||||
Febrile neutropenia | 1/7 (14.3%) | 0/7 (0%) | 1/8 (12.5%) | |||
Cardiac disorders | ||||||
Left ventricular systolic dysfunction | 0/7 (0%) | 0/7 (0%) | 1/8 (12.5%) | |||
Metabolism and nutrition disorders | ||||||
Hypercalcemia | 1/7 (14.3%) | 0/7 (0%) | 0/8 (0%) | |||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify | 1/7 (14.3%) | 0/7 (0%) | 0/8 (0%) | |||
Renal and urinary disorders | ||||||
Acute kidney injury | 0/7 (0%) | 0/7 (0%) | 1/8 (12.5%) | |||
Vascular disorders | ||||||
Hypotension | 0/7 (0%) | 0/7 (0%) | 1/8 (12.5%) | |||
Other (Not Including Serious) Adverse Events |
||||||
Pixantrone, 55mg/m^2 | Pixantrone, 85mg/m^2 | Pixantrone, 115mg/m^2 | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 7/7 (100%) | 7/7 (100%) | 8/8 (100%) | |||
Blood and lymphatic system disorders | ||||||
Anemia | 2/7 (28.6%) | 0/7 (0%) | 5/8 (62.5%) | |||
Febrile neutropenia | 1/7 (14.3%) | 0/7 (0%) | 1/8 (12.5%) | |||
Cardiac disorders | ||||||
Atrial fibrillation | 0/7 (0%) | 1/7 (14.3%) | 1/8 (12.5%) | |||
Cardiac disorders - Other, specify | 1/7 (14.3%) | 0/7 (0%) | 0/8 (0%) | |||
Chest pain - cardiac | 0/7 (0%) | 0/7 (0%) | 2/8 (25%) | |||
Sinus tachycardia | 0/7 (0%) | 0/7 (0%) | 4/8 (50%) | |||
Ear and labyrinth disorders | ||||||
Ear and labyrinth disorders - Other, specify | 0/7 (0%) | 0/7 (0%) | 1/8 (12.5%) | |||
Eye disorders | ||||||
Dry eye | 0/7 (0%) | 0/7 (0%) | 1/8 (12.5%) | |||
Watering eyes | 0/7 (0%) | 1/7 (14.3%) | 0/8 (0%) | |||
Gastrointestinal disorders | ||||||
Abdominal pain | 1/7 (14.3%) | 0/7 (0%) | 1/8 (12.5%) | |||
Bloating | 1/7 (14.3%) | 0/7 (0%) | 1/8 (12.5%) | |||
Constipation | 3/7 (42.9%) | 1/7 (14.3%) | 1/8 (12.5%) | |||
Diarrhea | 0/7 (0%) | 1/7 (14.3%) | 0/8 (0%) | |||
Dry mouth | 0/7 (0%) | 0/7 (0%) | 3/8 (37.5%) | |||
Dyspepsia | 1/7 (14.3%) | 0/7 (0%) | 0/8 (0%) | |||
Gastroesophageal reflux disease | 1/7 (14.3%) | 0/7 (0%) | 2/8 (25%) | |||
Mucositis oral | 0/7 (0%) | 0/7 (0%) | 1/8 (12.5%) | |||
Nausea | 4/7 (57.1%) | 1/7 (14.3%) | 3/8 (37.5%) | |||
Oral pain | 0/7 (0%) | 0/7 (0%) | 1/8 (12.5%) | |||
Vomiting | 2/7 (28.6%) | 0/7 (0%) | 4/8 (50%) | |||
General disorders | ||||||
Edema limbs | 0/7 (0%) | 0/7 (0%) | 1/8 (12.5%) | |||
Fatigue | 5/7 (71.4%) | 2/7 (28.6%) | 6/8 (75%) | |||
Fever | 0/7 (0%) | 0/7 (0%) | 1/8 (12.5%) | |||
Gait disturbance | 0/7 (0%) | 0/7 (0%) | 1/8 (12.5%) | |||
General disorders and administration site conditions - Other, specify | 0/7 (0%) | 0/7 (0%) | 1/8 (12.5%) | |||
Infusion site extravasation | 0/7 (0%) | 0/7 (0%) | 1/8 (12.5%) | |||
Injection site reaction | 0/7 (0%) | 0/7 (0%) | 1/8 (12.5%) | |||
Localized edema | 0/7 (0%) | 0/7 (0%) | 1/8 (12.5%) | |||
Malaise | 1/7 (14.3%) | 0/7 (0%) | 0/8 (0%) | |||
Non-cardiac chest pain | 1/7 (14.3%) | 0/7 (0%) | 0/8 (0%) | |||
Pain | 1/7 (14.3%) | 0/7 (0%) | 0/8 (0%) | |||
Infections and infestations | ||||||
Gum infection | 0/7 (0%) | 0/7 (0%) | 1/8 (12.5%) | |||
Investigations | ||||||
Alanine aminotransferase increased | 0/7 (0%) | 0/7 (0%) | 1/8 (12.5%) | |||
Alkaline phosphatase increased | 0/7 (0%) | 0/7 (0%) | 2/8 (25%) | |||
Aspartate aminotransferase increased | 0/7 (0%) | 0/7 (0%) | 3/8 (37.5%) | |||
Creatinine increased | 0/7 (0%) | 0/7 (0%) | 1/8 (12.5%) | |||
Electrocardiogram QT corrected interval prolonged | 0/7 (0%) | 0/7 (0%) | 1/8 (12.5%) | |||
Neutrophil count decreased | 1/7 (14.3%) | 1/7 (14.3%) | 4/8 (50%) | |||
Platelet count decreased | 2/7 (28.6%) | 0/7 (0%) | 5/8 (62.5%) | |||
Urine output decreased | 0/7 (0%) | 0/7 (0%) | 1/8 (12.5%) | |||
Weight loss | 2/7 (28.6%) | 0/7 (0%) | 0/8 (0%) | |||
White blood cell decreased | 0/7 (0%) | 0/7 (0%) | 3/8 (37.5%) | |||
Metabolism and nutrition disorders | ||||||
Anorexia | 4/7 (57.1%) | 2/7 (28.6%) | 1/8 (12.5%) | |||
Hypercalcemia | 2/7 (28.6%) | 0/7 (0%) | 2/8 (25%) | |||
Hyperglycemia | 0/7 (0%) | 1/7 (14.3%) | 0/8 (0%) | |||
Hypoalbuminemia | 0/7 (0%) | 0/7 (0%) | 1/8 (12.5%) | |||
Hypocalcemia | 0/7 (0%) | 0/7 (0%) | 1/8 (12.5%) | |||
Hypokalemia | 0/7 (0%) | 0/7 (0%) | 3/8 (37.5%) | |||
Hypomagnesemia | 0/7 (0%) | 0/7 (0%) | 1/8 (12.5%) | |||
Hyponatremia | 0/7 (0%) | 0/7 (0%) | 2/8 (25%) | |||
Musculoskeletal and connective tissue disorders | ||||||
Abdominal soft tissue necrosis | 0/7 (0%) | 0/7 (0%) | 1/8 (12.5%) | |||
Back pain | 0/7 (0%) | 0/7 (0%) | 5/8 (62.5%) | |||
Bone pain | 0/7 (0%) | 1/7 (14.3%) | 0/8 (0%) | |||
Neck pain | 0/7 (0%) | 1/7 (14.3%) | 0/8 (0%) | |||
Pain in extremity | 3/7 (42.9%) | 0/7 (0%) | 1/8 (12.5%) | |||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
Tumor pain | 0/7 (0%) | 0/7 (0%) | 1/8 (12.5%) | |||
Nervous system disorders | ||||||
Dizziness | 0/7 (0%) | 0/7 (0%) | 2/8 (25%) | |||
Dysgeusia | 1/7 (14.3%) | 0/7 (0%) | 2/8 (25%) | |||
Paresthesia | 0/7 (0%) | 0/7 (0%) | 4/8 (50%) | |||
Psychiatric disorders | ||||||
Anxiety | 1/7 (14.3%) | 0/7 (0%) | 1/8 (12.5%) | |||
Depression | 0/7 (0%) | 0/7 (0%) | 2/8 (25%) | |||
Psychiatric disorders - Other, specify | 0/7 (0%) | 0/7 (0%) | 1/8 (12.5%) | |||
Renal and urinary disorders | ||||||
Hematuria | 0/7 (0%) | 1/7 (14.3%) | 1/8 (12.5%) | |||
Proteinuria | 0/7 (0%) | 0/7 (0%) | 1/8 (12.5%) | |||
Urinary retention | 1/7 (14.3%) | 0/7 (0%) | 0/8 (0%) | |||
Urine discoloration | 0/7 (0%) | 0/7 (0%) | 1/8 (12.5%) | |||
Reproductive system and breast disorders | ||||||
Gynecomastia | 0/7 (0%) | 0/7 (0%) | 1/8 (12.5%) | |||
Reproductive system and breast disorders - Other, specify | 0/7 (0%) | 0/7 (0%) | 1/8 (12.5%) | |||
Respiratory, thoracic and mediastinal disorders | ||||||
Cough | 0/7 (0%) | 0/7 (0%) | 3/8 (37.5%) | |||
Dyspnea | 3/7 (42.9%) | 1/7 (14.3%) | 3/8 (37.5%) | |||
Epistaxis | 0/7 (0%) | 0/7 (0%) | 1/8 (12.5%) | |||
Pleural effusion | 0/7 (0%) | 0/7 (0%) | 1/8 (12.5%) | |||
Postnasal drip | 0/7 (0%) | 0/7 (0%) | 1/8 (12.5%) | |||
Skin and subcutaneous tissue disorders | ||||||
Alopecia | 1/7 (14.3%) | 0/7 (0%) | 0/8 (0%) | |||
Dry skin | 1/7 (14.3%) | 0/7 (0%) | 1/8 (12.5%) | |||
Rash maculo-papular | 0/7 (0%) | 0/7 (0%) | 2/8 (25%) |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | David Rizzieri, MD |
---|---|
Organization | Duke University Medical Center |
Phone | 919-668-1040 |
david.rizzieri@duke.edu |
- Pro00030834