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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT00006373
First received: October 4, 2000
Last updated: June 3, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Lymphoma
Drug: etoposide
Drug: ifosfamide
Drug: topotecan hydrochloride
Procedure: autologous bone marrow transplantation
Drug: Mesna
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Progression-free survival as defined as the time from date of enrollment to the time of recurrence


Enrollment: 27
Study Start Date: February 2000
Study Completion Date: December 2011
Primary Completion Date: October 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TIME
Topotecan, Ifosfamide, Mesna and Etoposide
Drug: etoposide
Etoposide IV 500 mg/m2/day over 24 hours Days -5, -4, -3
Other Names:
  • vepesid(R)
  • VP-16
Drug: ifosfamide
Ifosfamide 3,333 mg/m2/day IV over 2 hours (total dose 10,000 mg/m2)Days -8, -7, -6
Other Name: Ifex(R)
Drug: topotecan hydrochloride
Topotecan 21.3 mg/m2/day (total dose 64 mg/m2 ) IV over 30 minutes Days -8, -7, -6
Other Name: topotecan
Procedure: autologous bone marrow transplantation Drug: Mesna
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
Other Name: Mesnex(R)

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.

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00006373

Locations
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612-9497
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Investigators
Study Chair: Steven C. Goldstein, MD H. Lee Moffitt Cancer Center and Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT00006373     History of Changes
Other Study ID Numbers: MCC-12246, MCC-12246, MCC-IRB-5670, SB-MCC-12246, NCI-G00-1865
Study First Received: October 4, 2000
Last Updated: June 3, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
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

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Etoposide
Etoposide phosphate
Isophosphamide mustard
Topotecan
Ifosfamide
Mesna
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Topoisomerase I Inhibitors
Protective Agents
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on October 01, 2014