Clinical trial NCT00002745: Aminocamptothecin in Treating Patients With Refractory or Recurrent Hodgkin's Disease or Non-Hodgkin's Lymphoma
Official title: PHASE II STUDY OF 9-AMINOCAMPTOTHECIN (9-AC/DMA, NSC# 603071) IN PREVIOUSLY TREATED HODGKIN'S DISEASE AND NON-HODGKIN'S LYMPHOMA: IWF GRADES A-H
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma
Keywords: Waldenstrom macroglobulinemia
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent small lymphocytic lymphoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2004-04-22
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Phase II trial to study the effectiveness of aminocamptothecin in treating patients who have refractory or recurrent Hodgkin's disease or non-Hodgkin's lymphoma. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

Detailed description: OBJECTIVES:

I. Evaluate the response rate and duration of response to aminocamptothecin (9-AC) in patients with refractory or relapsed Hodgkin's disease or non-Hodgkin's lymphoma.

II. Assess the toxicity of 9-AC in these patients. III. Validate a preliminary pharmacodynamic model relating total 9-AC concentration, albumin, and bilirubin to toxicity.

IV. Determine whether 9-AC concentrations correlate with response.

OUTLINE: Patients are stratified by disease histology (International Working Formulation (IWF) A-C vs IWF D-F) and center.

Patients receive aminocamptothecin IV continuously on days 1-3. Treatment repeats every 2 weeks for a minimum of 3 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve stable disease, partial response (PR), or complete response (CR) may receive 2 additional courses past best response (minimum of 6 courses if PR or CR). Patients are followed every 6 months for 2 years, and then annually thereafter.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically documented Hodgkin's disease (closed to accrual 4/15/2000) OR
* Histologically documented non-Hodgkin's lymphoma (NHL) of one of the following International Working Formulation (IWF) histologies:

  * Small lymphocytic (absolute lymphocyte count less than 5,000)
  * IWF A Follicular, predominantly small cleaved cell
  * IWF B Follicular mixed
  * IWF C Follicular large cell
  * IWF D\* Diffuse small cleaved cell
  * IWF E\* Diffuse mixed
  * IWF F\* Diffuse large cell
  * IWF G\* Large cell, immunoblastic
  * IWF H\* \* Accrual of patients with these diagnoses closed 4/15/2000
* Pathology review required within 60 days of registration
* Refractory to or relapsed after prior chemotherapy as follows:

  * Low-grade NHL (IWF A-C): 1 or 2 prior therapies
  * Intermediate-grade NHL (IWF D-H): 1 prior therapy (stratum closed 4/15/2000)
  * Hodgkin's disease: 1 or 2 prior therapies (stratum closed 4/15/2000)
* Treatment with the same drugs on 2 different schedules considered 1 therapy
* Measurable disease by physical exam or imaging studies
* Mass larger than 1 x 1 cm
* Documented progression required of previously irradiated lesions
* The following are not considered measurable:

  * Ascites or pleural effusion
  * Bone marrow involvement
  * Positive barium studies
  * Bony disease (lytic lesions noted)
  * No mantle cell or transformed lymphoma
  * No parenchymal or leptomeningeal CNS disease
* A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

* Age: 18 and over
* Performance status: CALGB 0-2
* Unless hypersplenism or biopsy-proven bone marrow involvement:

  * Absolute granulocyte count at least 1,500/mm3
  * Platelet count at least 100,000/mm3
* Bilirubin normal
* AST no greater than 4 times normal
* Creatinine normal
* No suspected HIV infection
* No second malignancy within past 5 years except:

  * Curatively treated carcinoma of the cervix
  * Curatively treated basal cell skin cancer
  * No uncontrolled infection or other serious medical condition
  * No psychiatric condition that precludes informed consent
  * Not pregnant or nursing
  * Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

* No prior allogeneic or autologous bone marrow transplant
* More than 3 weeks since chemotherapy (6 weeks since nitrosoureas, melphalan, or mitomycin)
* No prior camptothecin
* More than 3 weeks since radiotherapy

Primary outcomes:
measure: Response
timeFrame: 2 years post treatment
Secondary outcomes:
measure: Toxicity
timeFrame: day 1 of each cycle
measure: 9-AC/DMA concentrations
timeFrame: Pre-treatment cycle 1 and just prior to completion of cycle 1
Other outcomes:
Locations:
city: Washington
country: United States
facility: Walter Reed Army Medical Center
state: District of Columbia
city: Minneapolis
country: United States
facility: University of Minnesota Cancer Center
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University Barnard Cancer Center
state: Missouri
city: Camden
country: United States
facility: Cooper Cancer Institute
state: New Jersey
city: Paterson
country: United States
facility: St. Joseph's Hospital and Medical Center
state: New Jersey
Study officials:
affiliation: Washington University Siteman Cancer Center
name: Nancy L. Bartlett, MD
role: STUDY_CHAIR
References:
citation: Bartlett NL, Johnson JL, Wagner-Johnston N, Ratain MJ, Peterson BA; Cancer and Leukemia Group B. Phase II study of 9-aminocamptothecin in previously treated lymphomas: results of Cancer and Leukemia Group B 9551. Cancer Chemother Pharmacol. 2009 Apr;63(5):793-8. doi: 10.1007/s00280-008-0803-x. Epub 2008 Jul 23.