Phase I/II Study Of UCN-01 In Combination With Fludarabine In Patients With Relapsed Or Refractory Chronic Lymphocytic Leukemia Or Small Lymphocytic Lymphoma
Combination Chemotherapy in Treating Patients With Chronic Lymphocytic Leukemia or Lymphocytic Lymphoma
Sponsors
Source
University Health Network, Toronto
Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing
so they stop growing or die. Combining more than one drug may kill more cancer cells.
PURPOSE: Phase I/II trial to study the effectiveness of combining UCN-01 with fludarabine in
treating patients who have relapsed or refractory chronic lymphocytic leukemia or lymphocytic
lymphoma.
Detailed Description
OBJECTIVES:
- Determine the overall response rate in patients with relapsed or refractory chronic
lymphocytic leukemia (CLL) or small lymphocytic lymphoma treated with UCN-01 and
fludarabine.
- Assess the molecular changes in CLL cells in peripheral blood in patients treated with
this regimen.
- Determine the progression-free and overall survival of patients treated with this
regimen.
- Determine the toxicity of this regimen in these patients.
OUTLINE: This is a multicenter, dose-escalation study of UCN-01.
Patients receive UCN-01 IV over 3 hours on day 1 and fludarabine IV over 30-60 minutes on
days 1-5. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease
progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of UCN-01 until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3
or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 18-46
additional patients receive UCN-01 and fludarabine as above at the recommended phase II dose.
PROJECTED ACCRUAL: A total of 12 patients will be accrued for the phase I portion of this
study within 6 months. A total of 18-46 patients will be accrued for the phase II portion of
this study within 9-23 months.
Overall Status
Completed
Start Date
2002-06-01
Completion Date
N/A
Primary Completion Date
2003-12-01
Phase
Phase 1/Phase 2
Study Type
Interventional
Conditions
Intervention
Eligibility
Criteria
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed chronic lymphocytic leukemia (CLL) or B-cell
small lymphocytic lymphoma (SLL)
- CLL is defined as:
- Persistent lymphocytosis greater than 5,000/mm^3
- CD19/CD5/CD23 positive
- Kappa or lambda light chain restriction
- Refractory to or disease progression after 1 or 2 prior treatment regimens
- Retreatment with oral chlorambucil is allowed and considered a second regimen
- At least one of the chlorambucil treatments must be for 3 months or longer
- At least 4 courses of cyclophosphamide, vincristine, and prednisone with or
without doxorubicin allowed
- Patients may have received prior fludarabine as first- or second-line therapy if
there is evidence of at least partial response and time to progression after
initial fludarabine therapy was at least 12 months
- No CNS involvement by lymphoma
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-2 OR
- Karnofsky 60-100%
Life expectancy
- More than 3 months
Hematopoietic
- See Disease Characteristics
- Absolute neutrophil count at least 1,000/mm^3
- Platelet count at least 100,000/mm^3
- No autoimmune hemolytic anemia or thrombocytopenia secondary to CLL or SLL requiring
ongoing therapy with prednisone or other immunosuppressive agents
Hepatic
- Bilirubin normal
- AST and ALT no greater than 2.5 times upper limit of normal
Renal
- Creatinine normal OR
- Creatinine clearance at least 60 mL/min
Cardiovascular
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
Pulmonary
- DLCO greater than 60% predicted
- FEV_1 greater than 70% predicted
- No significant underlying pulmonary disease
Other
- No other malignancy within the past 5 years except adequately treated basal cell skin
cancer or carcinoma in situ of the cervix
- No insulin-dependent diabetes mellitus
- No other uncontrolled concurrent illness
- No ongoing or active infection
- No pre-existing peripheral neuropathy grade 2 or greater
- No psychiatric illness or social situation that would preclude study compliance
- No prior allergic reactions to compounds of similar chemical or biological composition
to UCN-01 or other agents in this study
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- See Disease Characteristics
- At least 4 weeks since prior chemotherapy and recovered
Endocrine therapy
- See Hematopoietic
Radiotherapy
- No prior mediastinal radiation
- At least 4 weeks since prior radiotherapy and recovered
Surgery
- Not specified
Other
- No other concurrent investigational agents
- No concurrent combination antiretroviral therapy for HIV-positive patients
Gender
All
Minimum Age
18 Years
Maximum Age
N/A
Healthy Volunteers
No
Overall Official
Last Name |
Role |
Affiliation |
Michael R. Crump, MD, FRCPC |
Study Chair |
Princess Margaret Hospital, Canada |
Location
Facility |
McMaster Children's Hospital at Hamilton Health Sciences Hamilton Ontario L8N 3Z5 Canada |
London Health Sciences Centre London Ontario N6A 465 Canada |
Princess Margaret Hospital at University Health Network Toronto Ontario M5G 2M9 Canada |
Location Countries
Country
Canada
Verification Date
2015-07-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Responsible Party Type
Sponsor
Keywords
Has Expanded Access
No
Condition Browse
Secondary Id
CDR0000256600
NCI-5538
Intervention Browse
Mesh Term
Fludarabine
Fludarabine phosphate
7-hydroxystaurosporine
Firstreceived Results Date
N/A
Firstreceived Results Disposition Date
N/A
Study Design Info
Primary Purpose
Treatment
Study First Submitted
September 6, 2002
Study First Submitted Qc
January 26, 2003
Study First Posted
January 27, 2003
Last Update Submitted
July 22, 2015
Last Update Submitted Qc
July 22, 2015
Last Update Posted
July 23, 2015
ClinicalTrials.gov processed this data on December 10, 2019
Conditions
Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov,
conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.