Combination Chemotherapy in Treating Patients With Chronic Lymphocytic Leukemia or Lymphocytic Lymphoma

University Health Network, Toronto

Status and phase

Completed

Phase 2

Phase 1

Conditions

Lymphoma

Leukemia

Treatments

Drug: 7-hydroxystaurosporine

Drug: fludarabine phosphate

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00045513

CDR0000256600 (Registry Identifier)

PMH-PHL-006

NCI-5538

Details and patient eligibility

About

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.

Full 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.

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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