Dolastatin 10 in Treating Patients With Indolent Lymphoma, Waldenstrom's Macroglobulinemia, or Chronic Lymphocytic Leukemia

Sponsor

University of Vermont (Other)

Overall Status

Completed

CT.gov ID

NCT00005579

Collaborator

National Cancer Institute (NCI) (NIH)

Locations

Duration (Months)

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of dolastatin 10 in treating patients with indolent lymphoma, Waldenstrom's macroglobulinemia, or chronic lymphocytic leukemia.

Condition or Disease	Intervention/Treatment	Phase
Leukemia Lymphoma	Drug: dolastatin 10	Phase 2

Detailed Description

OBJECTIVES:

Estimate the efficacy of dolastatin 10 in patients with indolent lymphoma, Waldenstrom's macroglobulinemia, or chronic lymphocytic leukemia.
Evaluate the qualitative and quantitative toxicities of dolastatin 10 in this patient population.
Investigate the mechanism of action of dolastatin 10 in regards to apoptosis and effects of microtubules.

OUTLINE: This is an open-label, multicenter study. Patients are stratified by disease (chronic lymphocytic leukemia vs indolent lymphoma vs Waldenstrom's macroglobulinemia).

All patients receive dolastatin 10 IV bolus every 3 weeks. Patients continue treatment until disease progression, unacceptable toxicity, or patient's withdrawal from the study.

PROJECTED ACCRUAL: A maximum of 74 patients will be accrued for this study over 15 months.

Study Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase II Trial of Dolastin 10 in Indolent Lymphoma and Chronic Lymphocytic Leukemia

Study Start Date :

Jun 1, 1998

Actual Study Completion Date :

Feb 1, 2003

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologic or cytologic diagnosis of indolent lymphoma as defined by International Working Formulation categories A-C or diagnosis of Waldenstrom's macroglobulinemia, or chronic lymphocytic leukemia
Lymphoma must be stage III, IV, or recurrent (no primary CNS lymphoma or lymphomatous meningitis)
Waldenstrom's macroglobulinemia must have at least one of the following:
IGM greater than 3,000 mg/dL
Hemoglobin less than 10.0 g/dL
Bone marrow involvement greater than 30% lymphocytes
At least 2 cm lymphadenopathy
Serum viscosity greater than 3.0
Chronic lymphocytic leukemia must be intermediate or high risk stages I-IV and have progressed on fludarabine therapy unless patient cannot tolerate fludarabine
Intermediate risk group must have at least one indication of active disease:
Presence of any one of the disease related B symptoms: 10% or more loss of body weight over the preceding 6 month period, extreme fatigue, fever above 100 degrees F without evidence of infection, or night sweats
Massive (greater than 6 cm below left costal margin) or progressive splenomegaly
Massive (greater than 10 cm in longest diameter) or progressive lymphadenopathy
Progressive lymphocytosis with an increase of 50% over a 2 month period or anticipated doubling time of less than 12 months
Evidence of progressive marrow failure as manifested by the development or worsening of anemia and/or thrombocytopenia
Autoimmune anemia and/or thrombocytopenia poorly responsive to corticosteroid therapy
Intolerance, relapse, or failure following prior fludarabine allowed
Measurable or evaluable disease
No untreated immediate life threatening tumor complications

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

CALGB 0-2

Life expectancy:

Not specified

Hematopoietic:

See Disease Characteristics
WBC at least 4,000/mm^3*
Absolute granulocyte count at least 1,500/mm^3*
Platelet count at least 100,000/mm^3*
Hemoglobin at least 9 g/dL* NOTE: *Unless documented bone marrow involvement

Hepatic:

Bilirubin no greater than 1.5 mg/dL
SGOT no greater than 2.5 times upper limit of normal

Renal:

Creatinine no greater than 1.5 mg/dL OR
Creatinine clearance at least 60 mL/min

Other:

No prior malignancy except adequately treated basal or squamous cell skin cancer, carcinoma in situ of the cervix, well differentiated stage IA prostate cancer, or any other cancer from which the patient has been disease free for five years
Not pregnant or nursing
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

No prior autologous bone marrow or stem cell transplantation

Chemotherapy:

See Disease Characteristics
No more than 2 prior systemic regimens for treatment of lymphoma
No chemotherapy for treatment of any other prior malignancy
At least 4 weeks since chemotherapy and recovered
Prior fludarabine therapy allowed

Endocrine therapy:

See Disease Characteristics

Radiotherapy:

Prior radiotherapy allowed (index lesion cannot be within prior radiotherapy field)

Surgery:

Recovered from prior surgery

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Marlene and Stewart Greenebaum Cancer Center, University of Maryland	Baltimore	Maryland	United States	21201
2	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201-1379
3	Arthur G. James Cancer Hospital - Ohio State University	Columbus	Ohio	United States	43210-1240
4	Vermont Cancer Center	Burlington	Vermont	United States	05401-3498