Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Aminocamptothecin in Treating Patients With Refractory or Recurrent Hodgkin's Disease or Non-Hodgkin's Lymphoma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	18 and over	NCI	CLB-9551 NCT00002745, CALGB-9551

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.

Entry 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.

Prior/Concurrent Therapy:

Biologic therapy:
 No prior allogeneic or autologous bone marrow transplant  

Chemotherapy:
 See Disease Characteristics
 More than 3 weeks since chemotherapy (6 weeks since nitrosoureas,
  melphalan, or mitomycin)
 No prior camptothecin

Endocrine therapy:
 Not specified

Radiotherapy:
 More than 3 weeks since radiotherapy
  
Surgery:
 Not specified

Patient Characteristics:

Age:
 18 and over

Performance status:
 CALGB 0-2

Hematopoietic:
 (Unless hypersplenism or biopsy-proven bone marrow involvement)
 Absolute granulocyte count at least 1,500/mm3
 Platelet count at least 100,000/mm3

Hepatic:
 Bilirubin normal
 AST no greater than 4 times normal

Renal:
 Creatinine normal

Other:
 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

Expected Enrollment

A minimum of 110 eligible patients (40 with low grade non-Hodgkin's lymphoma 
(NHL), 35 with intermediate grade NHL, and 35 with Hodgkin's disease) will be 
accrued over 2.5 years.  Accrual of patients with intermediate grade NHL and 
Hodgkin's disease closed effective 04/15/2000.

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.

Bartlett NL, Johnson JL, Wagner-Johnston N, et al.: Phase II study of 9-aminocamptothecin in previously treated lymphomas: results of Cancer and Leukemia Group B 9551. Cancer Chemother Pharmacol 63 (5): 793-8, 2009.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Cancer and Leukemia Group B

Nancy Bartlett, MD, Protocol chair		Ph: 314-362-5654; 800-600-3606

Registry Information
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
Trial Start Date		1996-04-03
Trial Completion Date		2008-07-23
Registered in ClinicalTrials.gov		NCT00002745
Date Submitted to PDQ		1996-04-03
Information Last Verified		2008-10-29
NCI Grant/Contract Number		U10-CA31946