search
Back to results

Combination Chemotherapy Followed by Bone Marrow or Peripheral Stem Cell Transplantation in Treating Patients With Non-Hodgkin's Lymphoma or Hodgkin's Lymphoma

Primary Purpose

Lymphoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
etoposide
ifosfamide
topotecan hydrochloride
autologous bone marrow transplantation
Mesna
Sponsored by
H. Lee Moffitt Cancer Center and Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring stage III adult Hodgkin lymphoma, stage IV adult Hodgkin lymphoma, recurrent adult Hodgkin lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult Burkitt lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma

Eligibility Criteria

18 Years - 64 Years (Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Histologically confirmed non-Hodgkin's lymphoma No lymphoblastic lymphoma Under 55 years of age: Intermediate and high grade or aggressive disease that has relapsed and/or failed at least 2 salvage chemotherapy regimens OR Failed to achieve complete response after first line induction chemotherapy and failed at least 1 salvage chemotherapy regimen Low grade or indolent disease that has relapsed or failed to achieve complete response after first line induction chemotherapy and failed more than 2 salvage chemotherapy regimens 55 years of age and over: Intermediate and high grade or aggressive disease that has relapsed and/or failed to achieve complete response after first line induction chemotherapy Low grade or indolent disease that has relapsed or failed to achieve complete response after first line induction chemotherapy OR Histologically confirmed Hodgkin's lymphoma Under 55 years of age: Received at least 2 prior salvage chemotherapy regimens 55 years of age and over: Stage III or IV disease that has relapsed or failed to achieve remission after combination induction chemotherapy Prior primary radiotherapy allowed if relapse is high risk (e.g., recurrence in radiation field, B symptoms, or liver or bone marrow involvement) No active leptomeningeal involvement or severe symptomatic CNS disease Prior CSF tumor involvement allowed if asymptomatic and no evidence of disease on lumbar puncture or no tumor involvement on MRI of the brain Solid tumors and brain metastases allowed No evidence of disease by MRI and physical exam following optimal prior surgery and/or radiotherapy AND At least 3 months since prior radiotherapy NOTE: 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 to 64 Performance status: ECOG 0-1 Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Bilirubin no greater than 2.0 mg/dL* SGOT or SGPT no greater than 2.5 times normal* No severe hepatic dysfunction NOTE: *Unless due to primary malignancy Renal: Creatinine no greater than 2.0 mg/dL OR Creatinine clearance at least 60 mL/min Cardiovascular: No severe cardiac dysfunction Ejection fraction at least 50% by MUGA scan Essential hypertension controlled by medication allowed Pulmonary: DLCO at least 50% of normal OR No symptomatic obstructive or restrictive disease Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier contraception No active infection HIV negative No insulin dependent diabetes mellitus No uncompensated major thyroid or adrenal dysfunction No significant skin breakdown from tumor or other disease No other prior malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease Characteristics Prior doxorubicin or daunorubicin allowed if total dose no greater than 450 mg/m2 No prior topotecan Endocrine therapy: Not specified Radiotherapy: See Disease Characteristics Surgery: See Disease Characteristics Other: No concurrent nitroglycerin preparations for angina pectoris No concurrent antiarrhythmic drugs for major ventricular arrhythmias

Sites / Locations

  • H. Lee Moffitt Cancer Center and Research Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

TIME

Arm Description

Topotecan, Ifosfamide, Mesna and Etoposide

Outcomes

Primary Outcome Measures

Progression-free survival
Progression-free survival as defined as the time from date of enrollment to the time of recurrence

Secondary Outcome Measures

Full Information

First Posted
October 4, 2000
Last Updated
June 3, 2013
Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT00006373
Brief Title
Combination Chemotherapy Followed by Bone Marrow or Peripheral Stem Cell Transplantation in Treating Patients With Non-Hodgkin's Lymphoma or Hodgkin's Lymphoma
Official Title
A Phase II Study of Intensive-Dose Topotecan, Ifosfamide/Mesna and Etoposide (Vepesid)(TIME) Followed by Autologous Stem Cell Rescue in High Risk Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
June 2013
Overall Recruitment Status
Completed
Study Start Date
February 2000 (undefined)
Primary Completion Date
October 2006 (Actual)
Study Completion Date
December 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell or bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy followed by autologous bone marrow transplantation or peripheral stem cell transplantation in treating patients who have non-Hodgkin's lymphoma or Hodgkin's lymphoma.
Detailed Description
OBJECTIVES: Determine the efficacy of intensive high dose chemotherapy consisting of topotecan, ifosfamide, and etoposide followed by autologous bone marrow or peripheral blood stem cell transplantation in terms of response rate, progression free survival, and overall survival in patients with high risk non-Hodgkin's lymphoma or Hodgkin's lymphoma. Determine the pharmacokinetic profile of high dose topotecan and etoposide in these patients. Determine the pharmacodynamics and toxicity of this regimen in these patients. Determine the role of either an up or down regulation of DNA topoisomerase I or II amount and/or activity in terms of clinical response and toxicity in patients treated with this regimen. OUTLINE: Patients receive intensive high dose chemotherapy consisting of ifosfamide IV over 2 hours followed by topotecan IV over 30 minutes on days -8 to -6 and etoposide IV continuously over 24 hours on days -5 to -3. Patients undergo autologous bone marrow or peripheral blood stem cell transplantation on day 0. Patients are followed at 3, 6, and 12 months, annually until disease relapse, and then every 6 months until death. PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 3 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma
Keywords
stage III adult Hodgkin lymphoma, stage IV adult Hodgkin lymphoma, recurrent adult Hodgkin lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult Burkitt lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
27 (Actual)

8. Arms, Groups, and Interventions

Arm Title
TIME
Arm Type
Experimental
Arm Description
Topotecan, Ifosfamide, Mesna and Etoposide
Intervention Type
Drug
Intervention Name(s)
etoposide
Other Intervention Name(s)
vepesid(R), VP-16
Intervention Description
Etoposide IV 500 mg/m2/day over 24 hours Days -5, -4, -3
Intervention Type
Drug
Intervention Name(s)
ifosfamide
Other Intervention Name(s)
Ifex(R)
Intervention Description
Ifosfamide 3,333 mg/m2/day IV over 2 hours (total dose 10,000 mg/m2)Days -8, -7, -6
Intervention Type
Drug
Intervention Name(s)
topotecan hydrochloride
Other Intervention Name(s)
topotecan
Intervention Description
Topotecan 21.3 mg/m2/day (total dose 64 mg/m2 ) IV over 30 minutes Days -8, -7, -6
Intervention Type
Procedure
Intervention Name(s)
autologous bone marrow transplantation
Intervention Type
Drug
Intervention Name(s)
Mesna
Other Intervention Name(s)
Mesnex(R)
Intervention Description
Mesna 1,111 mg/m2/dose IV over 30 minutes; 30 minutes before and 4 and 8 hours after ifosfamide (total dose 10,000 mg/m2) Days -8, -7, -6
Primary Outcome Measure Information:
Title
Progression-free survival
Description
Progression-free survival as defined as the time from date of enrollment to the time of recurrence
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically confirmed non-Hodgkin's lymphoma No lymphoblastic lymphoma Under 55 years of age: Intermediate and high grade or aggressive disease that has relapsed and/or failed at least 2 salvage chemotherapy regimens OR Failed to achieve complete response after first line induction chemotherapy and failed at least 1 salvage chemotherapy regimen Low grade or indolent disease that has relapsed or failed to achieve complete response after first line induction chemotherapy and failed more than 2 salvage chemotherapy regimens 55 years of age and over: Intermediate and high grade or aggressive disease that has relapsed and/or failed to achieve complete response after first line induction chemotherapy Low grade or indolent disease that has relapsed or failed to achieve complete response after first line induction chemotherapy OR Histologically confirmed Hodgkin's lymphoma Under 55 years of age: Received at least 2 prior salvage chemotherapy regimens 55 years of age and over: Stage III or IV disease that has relapsed or failed to achieve remission after combination induction chemotherapy Prior primary radiotherapy allowed if relapse is high risk (e.g., recurrence in radiation field, B symptoms, or liver or bone marrow involvement) No active leptomeningeal involvement or severe symptomatic CNS disease Prior CSF tumor involvement allowed if asymptomatic and no evidence of disease on lumbar puncture or no tumor involvement on MRI of the brain Solid tumors and brain metastases allowed No evidence of disease by MRI and physical exam following optimal prior surgery and/or radiotherapy AND At least 3 months since prior radiotherapy NOTE: 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 to 64 Performance status: ECOG 0-1 Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Bilirubin no greater than 2.0 mg/dL* SGOT or SGPT no greater than 2.5 times normal* No severe hepatic dysfunction NOTE: *Unless due to primary malignancy Renal: Creatinine no greater than 2.0 mg/dL OR Creatinine clearance at least 60 mL/min Cardiovascular: No severe cardiac dysfunction Ejection fraction at least 50% by MUGA scan Essential hypertension controlled by medication allowed Pulmonary: DLCO at least 50% of normal OR No symptomatic obstructive or restrictive disease Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier contraception No active infection HIV negative No insulin dependent diabetes mellitus No uncompensated major thyroid or adrenal dysfunction No significant skin breakdown from tumor or other disease No other prior malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease Characteristics Prior doxorubicin or daunorubicin allowed if total dose no greater than 450 mg/m2 No prior topotecan Endocrine therapy: Not specified Radiotherapy: See Disease Characteristics Surgery: See Disease Characteristics Other: No concurrent nitroglycerin preparations for angina pectoris No concurrent antiarrhythmic drugs for major ventricular arrhythmias
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven C. Goldstein, MD
Organizational Affiliation
H. Lee Moffitt Cancer Center and Research Institute
Official's Role
Study Chair
Facility Information:
Facility Name
H. Lee Moffitt Cancer Center and Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612-9497
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Combination Chemotherapy Followed by Bone Marrow or Peripheral Stem Cell Transplantation in Treating Patients With Non-Hodgkin's Lymphoma or Hodgkin's Lymphoma

We'll reach out to this number within 24 hrs