Trial Outcomes & Findings for Pentostatin, Cyclophosphamide, Rituximab, and Mitoxantrone in Treating Patients With Chronic Lymphocytic Leukemia or Other Low-Grade B-Cell Cancer (NCT NCT00546377)
NCT ID: NCT00546377
Last Updated: 2016-05-12
Results Overview
Complete response (CR): Absence of lymphadenopathy, hepatomegaly or splenomegaly by physical examination and appropriate radiographic techniques (if abnormal pre-treatment): it is recognized that some patients with lymphoid malignancies who achieve a CR may have mild persistent abnormalities on CT Scan. Such abnormalities if stable on subsequent scanning will not be viewed as persistent disease in patients who otherwise meet the criteria for CR. Response will be assessed on an ongoing basis, but at a minimum of prior to cycle four and following completion of all therapy. Patients who are removed from study early will have response status determined at time of removal from study. The major criteria for determination of response to therapy in patients with CLL include physical examination and examination of the peripheral blood and bone marrow. Radiographic studies are not required but those that were abnormal pre-treatment, will be repeated to document the degree of maximal response.
COMPLETED
PHASE1/PHASE2
50 participants
3 years
2016-05-12
Participant Flow
Participant milestones
| Measure |
Pentostatin,Cyclophosphamide,Rituximab & Mitoxantrone
To determine the dose of mitoxantrone that can be safely administered with pentostatin, cyclosphosphamide, and rituximab in previously treated patient with CLL and other low grade B-cell malignancies.
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|---|---|
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Overall Study
STARTED
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50
|
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Overall Study
COMPLETED
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43
|
|
Overall Study
NOT COMPLETED
|
7
|
Reasons for withdrawal
| Measure |
Pentostatin,Cyclophosphamide,Rituximab & Mitoxantrone
To determine the dose of mitoxantrone that can be safely administered with pentostatin, cyclosphosphamide, and rituximab in previously treated patient with CLL and other low grade B-cell malignancies.
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|---|---|
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Overall Study
Deemed ineligible
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1
|
|
Overall Study
Adverse Event
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6
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Baseline Characteristics
Pentostatin, Cyclophosphamide, Rituximab, and Mitoxantrone in Treating Patients With Chronic Lymphocytic Leukemia or Other Low-Grade B-Cell Cancer
Baseline characteristics by cohort
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Pentostatin,Cyclophosphamide,Rituximab & Mitoxantrone
n=43 Participants
To determine the dose of mitoxantrone that can be safely administered with pentostatin, cyclosphosphamide, and rituximab in previously treated patient with CLL and other low grade B-cell malignancies.
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|---|---|
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Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
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31 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
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12 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
35 Participants
n=5 Participants
|
|
Region of Enrollment
United States
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43 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 3 yearsComplete response (CR): Absence of lymphadenopathy, hepatomegaly or splenomegaly by physical examination and appropriate radiographic techniques (if abnormal pre-treatment): it is recognized that some patients with lymphoid malignancies who achieve a CR may have mild persistent abnormalities on CT Scan. Such abnormalities if stable on subsequent scanning will not be viewed as persistent disease in patients who otherwise meet the criteria for CR. Response will be assessed on an ongoing basis, but at a minimum of prior to cycle four and following completion of all therapy. Patients who are removed from study early will have response status determined at time of removal from study. The major criteria for determination of response to therapy in patients with CLL include physical examination and examination of the peripheral blood and bone marrow. Radiographic studies are not required but those that were abnormal pre-treatment, will be repeated to document the degree of maximal response.
Outcome measures
| Measure |
Pentostatin,Cyclophosphamide,Rituximab & Mitoxantrone
n=43 Participants
To determine the dose of mitoxantrone that can be safely administered with pentostatin, cyclosphosphamide, and rituximab in previously treated patient with CLL and other low grade B-cell malignancies.
|
|---|---|
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Overall Response
Complete Response
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11 participants
|
|
Overall Response
Partial Response
|
23 participants
|
|
Overall Response
Stable Disease
|
4 participants
|
|
Overall Response
Progression of Disease
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5 participants
|
PRIMARY outcome
Timeframe: 2 yearsThe MTD is defined as the highest dose studied for which the incidence of DLT is less than 33%. In the phase I portion of the trial, cohorts of 3-6 pts will receive pentostatin, cyclophosphamide and rituximab along with one of three potential dose levels of mitoxantrone. The following dose escalation scheme will be followed: If none of the initial three pts in a cohort experience a dose-limiting toxicity (grade 4 infection, or grade ≥ 3 non-hematologic toxicity that persists for 7 days or more) then a new cohort of three pts will be treated at the next higher dose level. If one of the three pts in a cohort experiences DLT, then up to three additional pts will be treated at the same dose level. If two or more pts in a cohort experience DLT, then the maximum tolerated dose (MTD) will have been exceeded, and no further dose escalation will occur. The previous dose level will be considered as the MTD.
Outcome measures
| Measure |
Pentostatin,Cyclophosphamide,Rituximab & Mitoxantrone
n=43 Participants
To determine the dose of mitoxantrone that can be safely administered with pentostatin, cyclosphosphamide, and rituximab in previously treated patient with CLL and other low grade B-cell malignancies.
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|---|---|
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Maximum Tolerated Dose (MTD) of Mitoxantrone
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10 mg/m2
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Adverse Events
Pentostatin,Cyclophosphamide,Rituximab & Mitoxantrone
Serious adverse events
| Measure |
Pentostatin,Cyclophosphamide,Rituximab & Mitoxantrone
n=43 participants at risk
To determine the dose of mitoxantrone that can be safely administered with pentostatin, cyclosphosphamide, and rituximab in previously treated patient with CLL and other low grade B-cell malignancies.
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|---|---|
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Immune system disorders
Allerg react/hypersens (incl drug fever)
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2.3%
1/43 • Number of events 1 • 7 years
|
|
Immune system disorders
Allerg rhinitis (w sneez, nas stuff, postnas drip)
|
2.3%
1/43 • Number of events 1 • 7 years
|
|
Gastrointestinal disorders
Colitis
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2.3%
1/43 • Number of events 1 • 7 years
|
|
Gastrointestinal disorders
Constipation
|
2.3%
1/43 • Number of events 1 • 7 years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
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2.3%
1/43 • Number of events 1 • 7 years
|
|
Skin and subcutaneous tissue disorders
Dermatology/Skin, other
|
2.3%
1/43 • Number of events 1 • 7 years
|
|
Gastrointestinal disorders
Diarrhea
|
2.3%
1/43 • Number of events 1 • 7 years
|
|
Nervous system disorders
Dizziness
|
2.3%
1/43 • Number of events 1 • 7 years
|
|
Gastrointestinal disorders
Dysphagia (Difficulty swallowing)
|
2.3%
1/43 • Number of events 1 • 7 years
|
|
Infections and infestations
Febrile neutropenia
|
16.3%
7/43 • Number of events 9 • 7 years
|
|
General disorders
Fever (in the absence of neutropenia)
|
11.6%
5/43 • Number of events 6 • 7 years
|
|
Endocrine disorders
Hot flashes/flushes
|
2.3%
1/43 • Number of events 1 • 7 years
|
|
Renal and urinary disorders
Incontinence, urinary
|
2.3%
1/43 • Number of events 1 • 7 years
|
|
Infections and infestations
Inf norm ANC/gr1/2 neut-Pneumonia(lung)
|
4.7%
2/43 • Number of events 2 • 7 years
|
|
Infections and infestations
Infection w/ Gr 3/4 neut, Colon
|
2.3%
1/43 • Number of events 1 • 7 years
|
|
Infections and infestations
Infection w/ Gr 3/4 neut, Sinus
|
2.3%
1/43 • Number of events 1 • 7 years
|
|
Infections and infestations
Infection w/ Gr 3/4 neut, Skin (cellulites)
|
2.3%
1/43 • Number of events 1 • 7 years
|
|
Infections and infestations
Infection, other
|
2.3%
1/43 • Number of events 1 • 7 years
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness - Whole body/general
|
2.3%
1/43 • Number of events 1 • 7 years
|
|
Gastrointestinal disorders
Nausea
|
7.0%
3/43 • Number of events 4 • 7 years
|
|
Blood and lymphatic system disorders
Neutrophils/granulocytes (ANC/AGC)
|
2.3%
1/43 • Number of events 1 • 7 years
|
|
Investigations
Pain - Abdomen NOS
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2.3%
1/43 • Number of events 1 • 7 years
|
|
Investigations
Pain - Head/headache
|
4.7%
2/43 • Number of events 3 • 7 years
|
|
Investigations
Pain - Neck
|
2.3%
1/43 • Number of events 1 • 7 years
|
|
Investigations
Pain - Pelvis
|
2.3%
1/43 • Number of events 1 • 7 years
|
|
Investigations
Pain - Throat/pharynx/larynx
|
2.3%
1/43 • Number of events 1 • 7 years
|
|
General disorders
Sweating (diaphoresis)
|
2.3%
1/43 • Number of events 1 • 7 years
|
|
Nervous system disorders
Syncope (fainting)
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2.3%
1/43 • Number of events 1 • 7 years
|
|
Cardiac disorders
Vasovagal episode
|
2.3%
1/43 • Number of events 1 • 7 years
|
|
Eye disorders
Vision-photophobia
|
2.3%
1/43 • Number of events 1 • 7 years
|
|
Gastrointestinal disorders
Vomiting
|
4.7%
2/43 • Number of events 3 • 7 years
|
Other adverse events
| Measure |
Pentostatin,Cyclophosphamide,Rituximab & Mitoxantrone
n=43 participants at risk
To determine the dose of mitoxantrone that can be safely administered with pentostatin, cyclosphosphamide, and rituximab in previously treated patient with CLL and other low grade B-cell malignancies.
|
|---|---|
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Metabolism and nutrition disorders
ALT, SGPT
|
20.9%
9/43 • Number of events 50 • 7 years
|
|
Metabolism and nutrition disorders
AST, SGOT
|
16.3%
7/43 • Number of events 40 • 7 years
|
|
Metabolism and nutrition disorders
Albumin, low (hypoalbuminemia)
|
18.6%
8/43 • Number of events 40 • 7 years
|
|
Metabolism and nutrition disorders
Alkaline phosphatase
|
9.3%
4/43 • Number of events 50 • 7 years
|
|
Metabolism and nutrition disorders
Bilirubin (hyperbilirubinemia)
|
7.0%
3/43 • Number of events 10 • 7 years
|
|
Metabolism and nutrition disorders
Creatinine
|
11.6%
5/43 • Number of events 15 • 7 years
|
|
General disorders
Fever (in the absence of neutropenia)
|
4.7%
2/43 • Number of events 2 • 7 years
|
|
Metabolism and nutrition disorders
Glucose, high (hyperglycemia)
|
72.1%
31/43 • Number of events 50 • 7 years
|
|
Metabolism and nutrition disorders
Hemoglobin
|
72.1%
31/43 • Number of events 100 • 7 years
|
|
Blood and lymphatic system disorders
INR
|
4.7%
2/43 • Number of events 5 • 7 years
|
|
Blood and lymphatic system disorders
Leukocytes (total WBC)
|
72.1%
31/43 • Number of events 150 • 7 years
|
|
Blood and lymphatic system disorders
Lymphopenia
|
65.1%
28/43 • Number of events 150 • 7 years
|
|
Gastrointestinal disorders
Nausea
|
4.7%
2/43 • Number of events 2 • 7 years
|
|
Blood and lymphatic system disorders
Neutrophils/granulocytes (ANC/AGC)
|
72.1%
31/43 • Number of events 150 • 7 years
|
|
Metabolism and nutrition disorders
Phosphate, low (hypophosphatemia)
|
30.2%
13/43 • Number of events 50 • 7 years
|
|
Blood and lymphatic system disorders
Platelets
|
46.5%
20/43 • Number of events 150 • 7 years
|
|
Metabolism and nutrition disorders
Potassium, high (hyperkalemia)
|
4.7%
2/43 • Number of events 5 • 7 years
|
|
Metabolism and nutrition disorders
Potassium, low (hypokalemia)
|
4.7%
2/43 • Number of events 3 • 7 years
|
|
Gastrointestinal disorders
Vomiting
|
4.7%
2/43 • Number of events 2 • 7 years
|
Additional Information
Dr. Renier Brentjens, Associate Attending
Memorial Sloan Kettering Cancer Center
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place