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Pentostatin, Cyclophosphamide, Rituximab, and Mitoxantrone in Treating Patients With Chronic Lymphocytic Leukemia or Other Low-Grade B-Cell Cancer

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ClinicalTrials.gov Identifier: NCT00546377
Recruitment Status : Completed
First Posted : October 18, 2007
Results First Posted : May 12, 2016
Last Update Posted : May 12, 2016
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Leukemia
Lymphoma
Interventions Biological: filgrastim
Biological: pegfilgrastim
Biological: rituximab
Biological: sargramostim
Drug: cyclophosphamide
Drug: mitoxantrone hydrochloride
Drug: pentostatin
Genetic: fluorescence in situ hybridization
Genetic: gene rearrangement analysis
Genetic: polymerase chain reaction
Genetic: protein expression analysis
Other: flow cytometry
Procedure: biopsy
Enrollment 50
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Pentostatin,Cyclophosphamide,Rituximab & Mitoxantrone
Hide Arm/Group Description 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.
Period Title: Overall Study
Started 50
Completed 43
Not Completed 7
Reason Not Completed
Deemed ineligible             1
Adverse Event             6
Arm/Group Title Pentostatin,Cyclophosphamide,Rituximab & Mitoxantrone
Hide Arm/Group Description 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.
Overall Number of Baseline Participants 43
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 43 participants
<=18 years
0
   0.0%
Between 18 and 65 years
31
  72.1%
>=65 years
12
  27.9%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 43 participants
Female
8
  18.6%
Male
35
  81.4%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 43 participants
43
1.Primary Outcome
Title Overall Response
Hide Description 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.
Time Frame 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pentostatin,Cyclophosphamide,Rituximab & Mitoxantrone
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 43
Measure Type: Number
Unit of Measure: participants
Complete Response 11
Partial Response 23
Stable Disease 4
Progression of Disease 5
2.Primary Outcome
Title Maximum Tolerated Dose (MTD) of Mitoxantrone
Hide Description The 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.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pentostatin,Cyclophosphamide,Rituximab & Mitoxantrone
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 43
Measure Type: Number
Unit of Measure: mg/m2
10
Time Frame 7 years
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Pentostatin,Cyclophosphamide,Rituximab & Mitoxantrone
Hide Arm/Group Description 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.
All-Cause Mortality
Pentostatin,Cyclophosphamide,Rituximab & Mitoxantrone
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Pentostatin,Cyclophosphamide,Rituximab & Mitoxantrone
Affected / at Risk (%) # Events
Total   19/43 (44.19%)    
Blood and lymphatic system disorders   
Neutrophils/granulocytes (ANC/AGC)   1/43 (2.33%)  1
Cardiac disorders   
Vasovagal episode   1/43 (2.33%)  1
Endocrine disorders   
Hot flashes/flushes   1/43 (2.33%)  1
Eye disorders   
Vision-photophobia   1/43 (2.33%)  1
Gastrointestinal disorders   
Colitis   1/43 (2.33%)  1
Constipation   1/43 (2.33%)  1
Diarrhea   1/43 (2.33%)  1
Dysphagia (Difficulty swallowing)   1/43 (2.33%)  1
Nausea   3/43 (6.98%)  4
Vomiting   2/43 (4.65%)  3
General disorders   
Fever (in the absence of neutropenia)   5/43 (11.63%)  6
Sweating (diaphoresis)   1/43 (2.33%)  1
Immune system disorders   
Allerg react/hypersens (incl drug fever)   1/43 (2.33%)  1
Allerg rhinitis (w sneez, nas stuff, postnas drip)   1/43 (2.33%)  1
Infections and infestations   
Febrile neutropenia   7/43 (16.28%)  9
Inf norm ANC/gr1/2 neut-Pneumonia(lung)   2/43 (4.65%)  2
Infection w/ Gr 3/4 neut, Colon   1/43 (2.33%)  1
Infection w/ Gr 3/4 neut, Sinus   1/43 (2.33%)  1
Infection w/ Gr 3/4 neut, Skin (cellulites)   1/43 (2.33%)  1
Infection, other   1/43 (2.33%)  1
Investigations   
Pain - Abdomen NOS   1/43 (2.33%)  1
Pain - Head/headache   2/43 (4.65%)  3
Pain - Neck   1/43 (2.33%)  1
Pain - Pelvis   1/43 (2.33%)  1
Pain - Throat/pharynx/larynx   1/43 (2.33%)  1
Musculoskeletal and connective tissue disorders   
Muscle weakness - Whole body/general   1/43 (2.33%)  1
Nervous system disorders   
Dizziness   1/43 (2.33%)  1
Syncope (fainting)   1/43 (2.33%)  1
Renal and urinary disorders   
Incontinence, urinary   1/43 (2.33%)  1
Respiratory, thoracic and mediastinal disorders   
Cough   1/43 (2.33%)  1
Skin and subcutaneous tissue disorders   
Dermatology/Skin, other   1/43 (2.33%)  1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Pentostatin,Cyclophosphamide,Rituximab & Mitoxantrone
Affected / at Risk (%) # Events
Total   43/43 (100.00%)    
Blood and lymphatic system disorders   
INR   2/43 (4.65%)  5
Leukocytes (total WBC)   31/43 (72.09%)  150
Lymphopenia   28/43 (65.12%)  150
Neutrophils/granulocytes (ANC/AGC)   31/43 (72.09%)  150
Platelets   20/43 (46.51%)  150
Gastrointestinal disorders   
Nausea   2/43 (4.65%)  2
Vomiting   2/43 (4.65%)  2
General disorders   
Fever (in the absence of neutropenia)   2/43 (4.65%)  2
Metabolism and nutrition disorders   
ALT, SGPT   9/43 (20.93%)  50
AST, SGOT   7/43 (16.28%)  40
Albumin, low (hypoalbuminemia)   8/43 (18.60%)  40
Alkaline phosphatase   4/43 (9.30%)  50
Bilirubin (hyperbilirubinemia)   9/43 (20.93%)  20
Bilirubin (hyperbilirubinemia)   3/43 (6.98%)  10
Creatinine   5/43 (11.63%)  15
Glucose, high (hyperglycemia)   31/43 (72.09%)  50
Hemoglobin   31/43 (72.09%)  100
Phosphate, low (hypophosphatemia)   13/43 (30.23%)  50
Potassium, high (hyperkalemia)   2/43 (4.65%)  5
Potassium, low (hypokalemia)   2/43 (4.65%)  3
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Dr. Renier Brentjens, Associate Attending
Organization: Memorial Sloan Kettering Cancer Center
Phone: +1212-639-7053
Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00546377     History of Changes
Other Study ID Numbers: 05-077
MSKCC-05077
First Submitted: October 17, 2007
First Posted: October 18, 2007
Results First Submitted: December 17, 2015
Results First Posted: May 12, 2016
Last Update Posted: May 12, 2016