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Phase I/II Study Of UCN-01 In Combination With Fludarabine In Patients With Relapsed Or Refractory Chronic Lymphocytic Leukemia Or Small Lymphocytic Lymphoma

Phase 1/Phase 2
18 Years
Open (Enrolling)
Leukemia, Lymphoma

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Trial Information

Phase I/II Study Of UCN-01 In Combination With Fludarabine In Patients With Relapsed Or Refractory Chronic Lymphocytic Leukemia Or Small Lymphocytic Lymphoma


- Determine the overall response rate in patients with relapsed or refractory chronic
lymphocytic leukemia (CLL) or small lymphocytic lymphoma treated with UCN-01 and

- 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

- 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

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.

Inclusion Criteria


- 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



- 18 and over

Performance status

- ECOG 0-2 OR

- Karnofsky 60-100%

Life expectancy

- More than 3 months


- 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


- Bilirubin normal

- AST and ALT no greater than 2.5 times upper limit of normal


- Creatinine normal OR

- Creatinine clearance at least 60 mL/min


- No symptomatic congestive heart failure

- No unstable angina pectoris

- No cardiac arrhythmia


- DLCO greater than 60% predicted

- FEV_1 greater than 70% predicted

- No significant underlying pulmonary disease


- 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


Biologic therapy

- Not specified


- See Disease Characteristics

- At least 4 weeks since prior chemotherapy and recovered

Endocrine therapy

- See Hematopoietic


- No prior mediastinal radiation

- At least 4 weeks since prior radiotherapy and recovered


- Not specified


- No other concurrent investigational agents

- No concurrent combination antiretroviral therapy for HIV-positive patients

Type of Study:


Study Design:

Primary Purpose: Treatment

Principal Investigator

Michael R. Crump, MD, FRCPC

Investigator Role:

Study Chair

Investigator Affiliation:

Princess Margaret Hospital, Canada


United States: Federal Government

Study ID:




Start Date:

June 2002

Completion Date:

Related Keywords:

  • Leukemia
  • Lymphoma
  • refractory chronic lymphocytic leukemia
  • recurrent small lymphocytic lymphoma
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Lymphoma