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Fludarabine, Bendamustine, and Rituximab in Treating Participants With Lymphoid Cancers Undergoing Stem Cell Transplant

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ClinicalTrials.gov Identifier: NCT00880815
Recruitment Status : Completed
First Posted : April 14, 2009
Last Update Posted : June 3, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
This phase I trial studies the best dose and how well bendamustine works with standard chemotherapy (fludarabine, rituximab) in treating participants with lymphoid cancers undergoing stem cell transplant. Drugs used in chemotherapy, such as fludarabine, bendamustine, and rituximab, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy before a stem cell transplant helps stop the growth of cancer cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the participant, they may help the participant's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes, the transplanted cells from a donor can make an immune response against the body's normal cells called graft versus host disease. Giving rituximab and methotrexate after the transplant may stop this from happening.

Condition or disease Intervention/treatment Phase
CD20 Positive Chronic Lymphocytic Leukemia Follicular Lymphoma Mantle Cell Lymphoma Marginal Zone Lymphoma Recurrent Diffuse Large B-Cell Lymphoma T-Cell Non-Hodgkin Lymphoma Procedure: Allogeneic Hematopoietic Stem Cell Transplantation Biological: Anti-Thymocyte Globulin Drug: Bendamustine Biological: Filgrastim Drug: Fludarabine Drug: Methotrexate Biological: Rituximab Drug: Tacrolimus Phase 1

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine engraftment and dose limiting toxicity (DLT) of bendamustine in patients with lymphoid malignancies undergoing non-myeloablative allogeneic hematopoietic transplantation.

SECONDARY OBJECTIVES:

I. To monitor the risk of graft-versus-host disease (GVHD) and clinical responses.

OUTLINE: This is a dose escalation study of bendamustine.

Participants receive rituximab intravenously (IV) over 5-7 hours on days -13 and -6, fludarabine IV over 1 hour and bendamustine IV over 1 hour on days -5 to -3, and tacrolimus IV starting on day -2 and orally (PO) after hospital discharge for 6 to 8 months. Participants with matched unrelated donor (MUD) receive thymoglobulin on days -2 and -1. Participants undergo allogenic stem cell transplant over 30-45 minutes on day 0. Participants receive rituximab IV over 5-7 hours on days 1 and 8 and methotrexate IV over 30 minutes on days 1, 3, and 6. Participants with MUD also receive methotrexate IV on day 11. Participants receive filgrastim (G-CSF) subcutaneously (SC) once daily starting on day 7 until white blood cell counts recover.

After completion of study treatment, participants are followed up every 3 months during year 1 and every 6 months for up to 3 years.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Fludarabine, Bendamustine, and Rituximab (FBR) Non-Myeloablative Allogeneic Conditioning for Patients With Lymphoid Malignancies
Actual Study Start Date : February 17, 2009
Actual Primary Completion Date : May 28, 2019
Actual Study Completion Date : May 28, 2019


Arm Intervention/treatment
Experimental: Treatment (chemotherapy, stem cell transplant, rituximab)
Participants receive rituximab IV over 5-7 hours on days -13 and -6, fludarabine IV over 1 hour and bendamustine IV over 1 hour on days -5 to -3, and tacrolimus IV starting on day -2 and PO after hospital discharge for 6 to 8 months. Participants with MUD receive thymoglobulin on days -2 and -1. Participants undergo allogenic stem cell transplant over 30-45 minutes on day 0. Participants receive rituximab IV over 5-7 hours on days 1 and 8 and methotrexate IV over 30 minutes on days 1, 3, and 6. Participants with MUD also receive methotrexate IV on day 11. Participants receive G-CSF SC once daily starting on day 7 until white blood cell counts recover.
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Undergo ASCT
Other Names:
  • Allogeneic Hematopoietic Cell Transplantation
  • Allogeneic Stem Cell Transplantation
  • HSC
  • HSCT

Biological: Anti-Thymocyte Globulin
Given IV
Other Names:
  • Antithymocyte Globulin
  • Antithymocyte Serum
  • ATG
  • ATGAM
  • ATS
  • Thymoglobulin

Drug: Bendamustine
Given IV
Other Name: SDX-105

Biological: Filgrastim
Given IV
Other Names:
  • FILGRASTIM, LICENSE HOLDER UNSPECIFIED
  • G-CSF
  • Neupogen
  • r-metHuG-CSF
  • Recombinant Methionyl Human Granulocyte Colony Stimulating Factor
  • rG-CSF
  • Tevagrastim

Drug: Fludarabine
Given IV
Other Name: Fluradosa

Drug: Methotrexate
Given IV
Other Names:
  • Abitrexate
  • Alpha-Methopterin
  • Amethopterin
  • Brimexate
  • CL 14377
  • CL-14377
  • Emtexate
  • Emthexat
  • Emthexate
  • Farmitrexat
  • Fauldexato
  • Folex
  • Folex PFS
  • Lantarel
  • Ledertrexate
  • Lumexon
  • Maxtrex
  • Medsatrexate
  • Metex
  • Methoblastin
  • Methotrexate LPF
  • Methotrexate Methylaminopterin
  • Methotrexatum
  • Metotrexato
  • Metrotex
  • Mexate
  • Mexate-AQ
  • MTX
  • Novatrex
  • Rheumatrex
  • Texate
  • Tremetex
  • Trexeron
  • Trixilem
  • WR-19039

Biological: Rituximab
Given IV
Other Names:
  • ABP 798
  • BI 695500
  • C2B8 Monoclonal Antibody
  • Chimeric Anti-CD20 Antibody
  • CT-P10
  • IDEC-102
  • IDEC-C2B8
  • IDEC-C2B8 Monoclonal Antibody
  • MabThera
  • Monoclonal Antibody IDEC-C2B8
  • PF-05280586
  • Rituxan
  • Rituximab Biosimilar ABP 798
  • Rituximab Biosimilar BI 695500
  • Rituximab Biosimilar CT-P10
  • Rituximab Biosimilar GB241
  • Rituximab Biosimilar IBI301
  • Rituximab Biosimilar PF-05280586
  • Rituximab Biosimilar RTXM83
  • Rituximab Biosimilar SAIT101
  • RTXM83

Drug: Tacrolimus
Given IV and PO
Other Names:
  • FK 506
  • Fujimycin
  • Hecoria
  • Prograf
  • Protopic




Primary Outcome Measures :
  1. Maximum tolerated dose of bendamustine [ Time Frame: Up to 30 days ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with CD20 + chronic lymphocytic leukemia (CLL), marginal zone, mantle cell and follicular lymphoma or T-cell lymphoid malignancies who are eligible for allogeneic transplantation.
  • Patients with relapsed diffuse large B-cell lymphoma may be included if they were not eligible for autologous transplantation.
  • A fully-matched sibling donor or matched unrelated donor.
  • Left ventricular ejection fraction (EF) > 40% with no uncontrolled arrhythmias or symptomatic heart disease.
  • Forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and diffusion capacity of the lung for carbon monoxide (DLCO) > 40%.
  • Serum creatinine < 1.6 mg/dL.
  • Serum bilirubin < 3 X upper limit of normal.
  • Serum glutamate pyruvate transaminase (SGPT) < 3 X upper limit of normal.
  • Voluntary signed, written Institutional Review Board (IRB)-approved informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
  • Men and women of reproductive potential must agree to follow accepted birth control methods for the duration of the study. Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. Male subject agrees to use an acceptable method for contraception for the duration of the study.

Exclusion Criteria:

  • Patient with active central nervous system (CNS) disease.
  • Pregnant (positive beta human chorionic gonadotropin [HCG] test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization) or currently breast-feeding. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
  • Known infection with human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV)-I, hepatitis B, or hepatitis C.
  • Patients with other malignancies diagnosed within 2 years prior to study day-13 (except skin squamous or basal cell carcinoma).
  • Active uncontrolled bacterial, viral or fungal infections.
  • History of stroke within 6 months.
  • Myocardial infarction within the past 6 months prior to study day 1, or has New York Heart Association (NYHA) class III or IV heart failure or arrhythmias, unstable angina, uncontrolled congestive heart failure or arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any electrocardiography (ECG) abnormality at screening must be documented by investigator as not medically relevant.
  • A prior allogeneic transplant.
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
  • Patient has received other investigational drugs within 3 weeks before enrollment.
  • Hypersensitivity to bendamustine.
  • Prior known refractoriness to bendamustine.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00880815


Locations
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United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Issa Khouri, MD M.D. Anderson Cancer Center

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00880815     History of Changes
Other Study ID Numbers: 2008-0246
NCI-2018-01844 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2008-0246 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: April 14, 2009    Key Record Dates
Last Update Posted: June 3, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Large B-Cell, Diffuse
Lymphoma, T-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia
Leukemia, B-Cell
Antibodies
Immunoglobulins
Rituximab
Methotrexate
Tacrolimus
Antibodies, Monoclonal
Fludarabine phosphate
Lenograstim
Sargramostim
Thymoglobulin
Antilymphocyte Serum
Antineoplastic Agents, Immunological