Rituximab in Addition to Autologous Transplantation With BEAM for Patients With Lymphoid Malignancies

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00472056
First received: May 9, 2007
Last updated: June 19, 2012
Last verified: June 2012
  Purpose

Cohort 1: Patients who are less than or equal to 65 years of age.

1. To determine the disease-free survival (DFS) in the 2 arms (standard dose versus high dose rituximab)

Cohort 2: Patients who are older than 65 years of age

  1. To determine the disease-free survival (DFS) in the 2 arms (standard dose versus high dose rituximab)
  2. To determine the treatment related mortality (TRM)

Condition Intervention Phase
Lymphoma
Drug: Carmustine
Drug: Etoposide
Drug: Cytarabine
Drug: Melphalan
Drug: Rituximab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Trial Using Standard Dose Versus High Dose Rituximab in Addition to Autologous Transplantation With BEAM for Patients With Diffuse Large B Cell Lymphomas

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Disease-free Survival (DFS) [ Time Frame: Up to 5 years from transplant date. ] [ Designated as safety issue: Yes ]
    DFS defined as time from transplantation to disease relapse, disease progression, death during remission, or last follow-up. Evaluation at 3 months and 6 months after transplantation, then every 6 months for 3 years, and then once a year up to 5 years from the transplant date.


Enrollment: 93
Study Start Date: March 2005
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BEAM + Standard Rituximab

Arm 1 BEAM Chemotherapy (Carmustine, Etoposide, Cytarabine, Melphalan) + Standard Rituximab with Standard Rituximab for Cohort 1 or 2

Cohort 1 for 65 years of age or younger BEAM: Carmustine 300 mg/m2 intravenous (IV) over 1 hour on day -6, cytarabine 200 mg/m2 IV twice a day on days -5 through -2 (total 8 doses), etoposide 200 mg/m2 IV twice a day on days -5 through -2 (total 8 doses), and melphalan 140 mg/m2 IV on day -1.

Cohort 2 for older than 65 years of age BEAM: Carmustine 300 mg/m2 IV over 1 hour on day -6, cytarabine 100 mg/m2 IV twice a day on days -5 through -2 (total 8 doses), etoposide 100 mg/m2 IV twice a day on days -5 through -2 (total 8 doses), and melphalan 140 mg/m2 IV on day -1.

Standard Rituximab: 375 mg/m^2 IV Days +1, +8 after Stem Cell Infusion on Day 0.

Drug: Carmustine
300 mg/m^2 IV for 1 Day
Other Names:
  • BCNU
  • BiCNU
Drug: Etoposide
Arm 1 = 200 mg/m^2 IV Every 12 Hours x 4 Days; Arm 2 = 100 mg/m^2 IV Every 12 Hours x 4 Days
Other Name: VePesid
Drug: Cytarabine
Arm 1 = 200 mg/m^2 IV Every 12 Hours x 4 Days; Arm 2 = 100 mg/m^2 IV Every 12 Hours x 4 Days
Other Names:
  • Ara-C
  • Cytosar
  • DepoCyt
  • Cytosine arabinosine hydrochloride
Drug: Melphalan
140 mg/m^2 IV x 1 Day
Drug: Rituximab
Cohort 1, High-Dose Rituximab = 1000 mg/m^2 IV On Days +1 and +8 After Stem Cell Infusion; Cohort 2, Standard Dose Rituximab = 375 mg/m^2 IV On Days +1 and +8 After Stem Cell Infusion.
Other Name: Rituxan
Experimental: BEAM + High Rituximab

BEAM Chemotherapy (Carmustine, Etoposide, Cytarabine, Melphalan) + High Dose Rituximab

Cohort 1 for 65 years of age or younger BEAM: Carmustine 300 mg/m2 intravenous (IV) over 1 hour on day -6, cytarabine 200 mg/m2 IV twice a day on days -5 through -2 (total 8 doses), etoposide 200 mg/m2 IV twice a day on days -5 through -2 (total 8 doses), and melphalan 140 mg/m2 IV on day -1.

Cohort 2 for older than 65 years of age BEAM: Carmustine 300 mg/m2 IV over 1 hour on day -6, cytarabine 100 mg/m2 IV twice a day on days -5 through -2 (total 8 doses), etoposide 100 mg/m2 IV twice a day on days -5 through -2 (total 8 doses), and melphalan 140 mg/m2 IV on day -1.

High Dose Rituximab: 1000 mg/m^2 IV Days +1, +8 after Stem Cell Infusion on Day 0

Drug: Carmustine
300 mg/m^2 IV for 1 Day
Other Names:
  • BCNU
  • BiCNU
Drug: Etoposide
Arm 1 = 200 mg/m^2 IV Every 12 Hours x 4 Days; Arm 2 = 100 mg/m^2 IV Every 12 Hours x 4 Days
Other Name: VePesid
Drug: Cytarabine
Arm 1 = 200 mg/m^2 IV Every 12 Hours x 4 Days; Arm 2 = 100 mg/m^2 IV Every 12 Hours x 4 Days
Other Names:
  • Ara-C
  • Cytosar
  • DepoCyt
  • Cytosine arabinosine hydrochloride
Drug: Melphalan
140 mg/m^2 IV x 1 Day
Drug: Rituximab
Cohort 1, High-Dose Rituximab = 1000 mg/m^2 IV On Days +1 and +8 After Stem Cell Infusion; Cohort 2, Standard Dose Rituximab = 375 mg/m^2 IV On Days +1 and +8 After Stem Cell Infusion.
Other Name: Rituxan

Detailed Description:

Carmustine, cytarabine, etoposide, melphalan, and rituximab are all standard chemotherapy drugs.

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the toss of a coin) to one of two treatment groups. Participants in one group will receive high dose rituximab with transplantation and high dose chemotherapy. Participants in the other group will receive standard dose rituximab with transplantation and high dose chemotherapy. The first 10 patients enrolled on this study will have an equal chance of being assigned to either group. After the first 10 participants are enrolled, the remaining participants will have a higher chance of being assigned to the group that has proven to be more effective.

All participants will have a plastic tube (catheter) inserted under their collarbone. This catheter will be left in place for the entire treatment period. The catheter will be used to deliver most of the drugs and for the collection and transfusion of the stem cells. When possible, all drugs that need to be given by vein will be given using the catheter.

Stem cell collection is done on a separate study and patients will take part in this study only after the stem cell collection is complete. You should have an adequate number of stem cells collected and stored before you can be eligible for high-dose chemotherapy and transplantation.

All treatment will be given at M. D. Anderson. You will be admitted to the hospital to receive high dose chemotherapy and will stay in the hospital for 3-4 weeks. You will be given carmustine by vein over 1 hour on Day 1. On Days 2 - 5, you will be given cytarabine by vein over 1 hour and etoposide by vein over 3 hours. This will be repeated every 12 hours on Days 2-5. On Day 6, you will be given melphalan by vein over 30 minutes. On Day 7, the stem cells that were collected earlier will be given back to you ("transplanted") through the catheter over 30-45 minutes.

You will also receive either high dose or standard dose rituximab by vein over 4-6 hours one day after the transplant (Day 1) and then again 1 week later (Day 8).

You will receive G-CSF injections staring at Day 1 (one day after transplant or stem cell infusion). These will continue our cell count reaches the appropriate level for at least 3 days in a row. Blood tests (2 teaspoons) will be done every day while you are in the hospital to track the effects of the transplant.

You will be asked to return to M. D. Anderson at 3 months and 6 months after transplantation, then every 6 months for 3 years, and then once a year up to 5 years from the transplant date. At each visit you will get blood work (1-2 tablespoons), CT scans, and other tests like bone marrow (if needed) to determine the status of your lymphoma.

This is an investigational study. All of the drugs used in this study are FDA approved and are commercially available. Up to 100 patients will take part in this study. All will be enrolled at M. D. Anderson.

  Eligibility

Ages Eligible for Study:   up to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with histologically proven diffuse large B-cell (CD20 positive) or transformed follicular non-Hodgkin's lymphomas, that have relapsed after conventional chemotherapy and are not eligible for protocols of higher priority
  2. Patients must have chemosensitive disease to salvage chemotherapy and less than 5% bone marrow involvement with lymphoma by gross pathologic examination
  3. Age less than or equal to 80 years. There is no lower age limit for this study.
  4. Zubrod performance status of less than 2
  5. Negative pregnancy test in patients with child bearing potential
  6. Must be willing to sign informed consent
  7. Should be seronegative for HIV, hepatitis B surface antigen, hepatitis C antibody.

Exclusion Criteria:

  1. Patients with known active CNS disease are excluded. Patients with prior history of CNS disease should have a negative MRI of the brain (and/or spine if indicated) and negative CSF cytology within 4 weeks of enrollment into the study.
  2. Less than 3 weeks from last cytotoxic chemotherapy
  3. Serum bilirubin > 1.5 mg/dl
  4. Serum transaminases > 2X/ULN
  5. Serum creatinine > 1.6 mg/dl
  6. Failure to collect more than 3 x 1,000,000 CD34+ stem cells/kg body weight
  7. Left ventricular ejection fraction of < 40%, unless cleared by cardiology
  8. Corrected DLCO of < 50%
  9. Patients who are on anticoagulants or antiplatelet agents.
  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: NCT00472056

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Chitra M. Hosing, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00472056     History of Changes
Other Study ID Numbers: 2004-0271
Study First Received: May 9, 2007
Results First Received: January 9, 2012
Last Updated: June 19, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Non-Hodgkin's Lymphoma
Lymphoid Malignancies
Lymphoma
BEAM Chemotherapy
Carmustine
BCNU
BiCNU
Etoposide
VePesid
Cytarabine
Cytosar
DepoCyt
Cytosine arabinosine hydrochloride
Ara-C
Melphalan
Rituximab
Rituxan

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Large B-Cell, Diffuse
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Carmustine
Cytarabine
Etoposide
Etoposide phosphate
Melphalan
Rituximab
Alkylating Agents
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists

ClinicalTrials.gov processed this record on October 20, 2014