Combination Chemotherapy With or Without Total-Body Irradiation Followed By Stem Cell Transplant in Treating Patients With Non-Hodgkin Lymphoma

Lymphoma Clinical Trial

Official title:

High-Dose Therapy and Autologous Stem Cell Transplantation During Remission in Poor-Risk Age-Adjusted International Prognostic Index High and High-Intermediate Risk Group Patients With Intermediate Grade and High-Grade Non-Hodgkin's Lymphoma Including Mantle Cell Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00559104
• Other study ID #: 97133
• Secondary ID: P30CA033572CHNMC
• Status: Completed
• Phase: Phase 2
• First received: November 15, 2007
• Last updated: July 17, 2015
• Start date: October 1998
• Est. completion date: July 2011

Study information

• Verified date: July 2015
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Giving chemotherapy and radiation therapy to the entire body before an autologous peripheral stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. The patient's stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy and radiation therapy.

PURPOSE: This phase II trial is studying the side effects of giving combination chemotherapy together with or without total-body irradiation followed by a stem cell transplant and to see how well it works in treating patients with non-Hodgkin lymphoma.

Description:

OBJECTIVES:

• To evaluate the outcome of patients with poor-risk, age-adjusted International Prognostic Index high- and high-intermediate-risk, intermediate- and high-grade non-Hodgkin lymphoma undergoing high-dose therapy comprising etoposide and cyclophosphamide, either carmustine or total-body irradiation, and autologous stem cell transplantation (ASCT) given as a consolidation therapy.

• To evaluate the role of high-dose therapy and ASCT during first partial or complete remission (1PR/CR) in patients with poor-risk primary mediastinal large cell lymphoma.

• To evaluate the role of high-dose therapy and ASCT during first 1PR/CR in patients with advanced-stage mantle cell lymphoma.

• To evaluate the short-term and long-term toxicities of high-dose therapy and ASCT when performed during 1PR/CR in patients with poor-risk aggressive lymphomas.

OUTLINE: Patients are stratified according to disease (diffuse mixed, diffuse large cell, and immunoblastic lymphoma vs primary mediastinal large cell lymphoma vs small noncleaved cell lymphoma vs stage IV mantle cell lymphoma).

Patients' peripheral blood stem cells (PBSC) are collected after mobilization. A minimum of 2.0 x 10^6 CD34+ cells/kg must be collected. Patients experiencing disease progression during stem cell collection will be removed from study. Patients are assigned to undergo 1 of 2 therapeutic regimens.

• Regimen 1: Patients undergo total-body irradiation (TBI) on days -8 to -5 and receive etoposide IV over 4 hours on day -4 and cyclophosphamide IV over 2 hours on day -2. Patients undergo autologous PBSC transplantation on day 0.

• Regimen 2 (for patients who have received any prior thoracic irradiation or patients who underwent previous irradiation that precludes the use of TBI): Patients receive carmustine IV over 2 hours on days -7 to -5. Patients then receive etoposide and cyclophosphamide and undergo autologous PBSC transplantation as in regimen 1.

Patients with residual bulky disease greater than 5 cm may undergo involved-field radiotherapy before or after transplantation.

Patients are followed at days 7, 14, 21, 100 and 180 after PBSC transplantation, every 6 months for 3 years, and then annually thereafter.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years to 59 Years

Eligibility

Inclusion Criteria:

• DISEASE CHARACTERISTICS:

• Biopsy-proven diagnosis of high-grade (small noncleaved cell lymphoma [SNCCL] or immunoblastic lymphoma) or intermediate-grade non-Hodgkin lymphoma (NHL) including mantle cell lymphoma (MCL)

• SNCCL patients with all of the following factors at presentation of disease:

• Lactate dehydrogenase (LDH) > 500 IU/L

• Unresectable bulky mass > 10 cm

• Stage IV disease with bone marrow involvement

• MCL Patients with stage IV disease or in International Prognostic Index (IPI) high- or high-intermediate-risk group at the time of diagnosis

• Considered at diagnosis to be high- (3 risk factors) or high-intermediate-risk (2 risk factors) based on an age-adjusted IPI

• Poor prognostic factors at diagnosis include stage III or IV disease, lactate dehydrogenase (LDH) level above normal, or ECOG performance status (PS) 2-4

• Patients with primary mediastinal large cell lymphoma with or without sclerosis who at diagnosis had elevated LDH level with bulky mediastinal mass > 10 cm associated with a pleural effusion on chest radiography or computer tomography, or who have persistent mediastinal mass with positive disease by post-treatment gallium GA 67 scan

• Must have attained a complete response or partial response to first-line standard conventional chemotherapy

• ECOG PS 0-1 OR Karnofsky PS 80-100%

• Serum creatinine < 1.5 mg/dL OR creatinine clearance > 60 mL/min

• FEV_1 > 65% of predicted measurement or DLCO = 45% of predicted measurement

• Cardiac ejection fraction > 50% by echocardiogram

• Bilirubin = 1.5 x normal

• SGOT or SGPT = 2 x normal

Exclusion Criteria:

• Evidence of lymphoma or < 10% lymphomatous involvement of bone by bilateral bone marrow aspiration and biopsy

• Abnormal cytogenetic study of bone marrow aspirate sample NOTE: A new classification scheme for adult non-Hodgkin 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.

• Positive HIV antibody

• Prior malignancies except for adequately treated basal cell or squamous cell carcinoma of the skin

• Hepatitis B surface antigen positivity

• Prior bone marrow transplantation

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior bone marrow transplantation

Study Design

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell
• Lymphoma, Non-Hodgkin

Intervention

Drug:
• carmustine
Unique to the Carmustine in Conditioning arm
• cyclophosphamide
Used in Both Arms
• etoposide
Used in Both Arms

Procedure:
• autologous hematopoietic stem cell transplantation
Both arms are given autologous stem cell transplantation
• peripheral blood stem cell transplantation
Both arms are given peripheral blood stem cell transplantation (Peripheral blood stem cells are the material, autologous transplant is the modality).

Radiation:
• total-body irradiation
Unique to the Radiation in Conditioning Arm

Drug:
• G-CSF
G-CSF is given in both treatment arms, both to mobilize stem cells before apheresis, and to promote recovery of granulocytes after stem-cell re-infusion.

Locations

Country	Name	City	State
United States	City of Hope National Medical Center--Main Campus	Duarte	California
United States	Good Samaritan Regional Medical Center	Phoenix	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Nademanee A, Molina A, Dagis A, Snyder DS, O'Donnell MR, Parker P, Stein A, Smith E, Planas I, Kashyap A, Spielberger R, Fung H, Krishnan A, Bhatia R, Wong KK, Somlo G, Margolin K, Chow W, Sniecinski I, Vora N, Slovak M, Niland JC, Forman SJ. Autologous stem-cell transplantation for poor-risk and relapsed intermediate- and high-grade non-Hodgkin's lymphoma. Clin Lymphoma. 2000 Jun;1(1):46-54. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression	Event will be recorded if it occurs any time post-transplant, until date of death, last recorded contact, or end-of-study; whichever comes first.; Below is reported Progression-free Survival: event is relapse or progression, or death.	Assessed at date of progression post-transplant	No
Primary	Mortality	Event will be recorded if it occurs any time from the date of transplant until the end-of-study date, or the date of last contact, whichever comes first.	Assessed at date of death post-transplant	No
Secondary	Short-term and Long-term Treatment-related Toxicities	Patient may be assessed for toxicities any time after transplant, up to death, last contact date, or end-of-study date.	Any time after transplant	Yes