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

NCT ID: NCT00559104

Last Updated: 2015-08-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1998-10-31
• Study Completion Date: 2011-07-31

Brief 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.

Detailed 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.

Conditions

Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Irradiation in conditioning

total-body irradiation, etoposide, cyclophosphamide, infusion of peripheral blood stem cells, granulocyte-colony stimulating factor (G-CSF), autologous hematologic stem cell transplantation, peripheral blood stem cell transplantation

Group Type: ACTIVE_COMPARATOR

cyclophosphamide

Intervention Type: DRUG

Used in Both Arms

etoposide

Intervention Type: DRUG

Used in Both Arms

autologous hematopoietic stem cell transplantation

Intervention Type: PROCEDURE

Both arms are given autologous stem cell transplantation

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

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

total-body irradiation

Intervention Type: RADIATION

Unique to the Radiation in Conditioning Arm

G-CSF

Intervention Type: DRUG

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.

Carmustine in conditioning

Carmustine, etoposide, cyclophosphamide, infusion of peripheral blood stem cells, granulocyte-colony stimulating factor (G-CSF), autologous hematopoietic stem cell transplantation, peripheral blood stem cell transplantation

Group Type: ACTIVE_COMPARATOR

carmustine

Intervention Type: DRUG

Unique to the Carmustine in Conditioning arm

cyclophosphamide

Intervention Type: DRUG

Used in Both Arms

etoposide

Intervention Type: DRUG

Used in Both Arms

autologous hematopoietic stem cell transplantation

Intervention Type: PROCEDURE

Both arms are given autologous stem cell transplantation

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

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

G-CSF

Intervention Type: DRUG

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.

Interventions

carmustine

Unique to the Carmustine in Conditioning arm

Intervention Type: DRUG

cyclophosphamide

Used in Both Arms

Intervention Type: DRUG

etoposide

Used in Both Arms

Intervention Type: DRUG

autologous hematopoietic stem cell transplantation

Both arms are given autologous stem cell transplantation

Intervention Type: PROCEDURE

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).

Intervention Type: PROCEDURE

total-body irradiation

Unique to the Radiation in Conditioning Arm

Intervention Type: RADIATION

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.

Intervention Type: DRUG

Other Intervention Names

BCNU; Cytoxan, CTX; VP-16; Granulocyte-colony stimulating factor

Eligibility Criteria

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

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 59 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

City of Hope Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Auayporn P. Nademanee, MD

Role: STUDY_CHAIR

City of Hope Comprehensive Cancer Center

Locations

Good Samaritan Regional Medical Center

Phoenix, Arizona, United States

City of Hope National Medical Center--Main Campus

Duarte, California, United States

Countries

United States

References

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. doi: 10.3816/clm.2000.n.004.

Reference Type: BACKGROUND

PMID: 11707813 (View on PubMed)

Other Identifiers

P30CA033572

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CHNMC-97133

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000573523

Identifier Type: REGISTRY

Identifier Source: secondary_id

97133

Identifier Type: -

Identifier Source: org_study_id