Blood Stem Cell Transplant With Low Dose Chemotherapy for Relapsed Follicular Non-Hodgkin's Lymphoma (BMT CTN 0701)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00912223
Recruitment Status : Completed
First Posted : June 3, 2009
Results First Posted : November 21, 2016
Last Update Posted : October 27, 2017
National Heart, Lung, and Blood Institute (NHLBI)
Blood and Marrow Transplant Clinical Trials Network
National Cancer Institute (NCI)
National Marrow Donor Program
Information provided by (Responsible Party):
Medical College of Wisconsin

Brief Summary:
Blood stem cell transplants are one treatment option for people with lymphoma or other types of blood cancers. For this type of treatment, family members or unrelated donors with a similar tissue type usually donate their blood stem cells to the transplant patients. This study will evaluate the effectiveness of a type of blood stem cell transplant that uses lower doses of chemotherapy in people with relapsed follicular non-Hodgkin's lymphoma (NHL).

Condition or disease Intervention/treatment Phase
Lymphoma, Non-Hodgkin Biological: Hematopoietic Stem Cell Transplant Phase 2

Detailed Description:

Follicular NHL, a type of blood cancer, is the second most common type of non-Hodgkin's lymphoma, with approximately 15,000 new cases being diagnosed each year in the United States. Chemotherapy is a common treatment option for people with NHL, and at first most people achieve cancer remission with initial chemotherapy. However, after the initial chemotherapy, people with this disease typically experience a continuous pattern of relapse that results in progressively shorter remission durations. A blood stem cell transplant is another treatment option for people with follicular NHL. In a blood stem cell transplant procedure, healthy blood stem cells are taken from a donor and transplanted into the patient. The cells can be donated by a family member or an unrelated donor who has a similar tissue type. Typically, people who are undergoing a blood stem cell transplant receive high doses of chemotherapy before the transplant to prepare their bodies to accept the donor stem cells. In this study, participants will undergo a type of stem cell transplant called a nonmyeloablative transplant, which involves a reduced intensity method of transplantation that does not require high doses of chemotherapy. The purpose of the study is to examine the effectiveness of a nonmyeloablative allogeneic blood stem cell transplant at improving survival rates in people with relapsed follicular NHL.

This study will enroll people with relapsed follicular NHL. At a baseline study visit, participants will undergo a medical history review, physical examination, blood collection, lung function testing, computed tomography (CT) scans, a bone marrow biopsy, and questionnaires to assess quality of life. Participants will be admitted to the hospital and on various days in the 2 weeks before the transplant, they will receive fludarabine, cyclophosphamide, rituximab, which are cancer medications, and tacrolimus, a medication that will help prevent graft-versus-host disease (GVHD), which is an attack by the donor cells on the body's normal tissues. Participants will then undergo the blood stem cell transplant. At various times during the 2 weeks after the transplant, participants will receive rituximab and methotrexate, which is another medication to prevent GVHD. They will also receive tacrolimus for at least 6 months to help prevent GVHD. Participants will remain in the hospital for as long as necessary to recover from the transplant. Follow-up study visits will occur weekly for Weeks 1 to 14, and then at Months 6, 12, 18, and 24. At each study visit, select baseline procedures will be repeated.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 65 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Trial of Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation for Patients With Relapsed Follicular Non-Hodgkin's Lymphoma Beyond First Complete Response (BMT CTN #0701)
Study Start Date : April 2009
Actual Primary Completion Date : November 2014
Actual Study Completion Date : August 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: Hematopoietic Stem Cell Transplant
Participants will undergo a non-myeloablative allogeneic hematopoietic stem cell transplant.
Biological: Hematopoietic Stem Cell Transplant

NOTE: The - sign is the number of days before the transplant and the + sign is the number of days after the transplant.

The conditioning regimen will consist of the following:

  • Rituxan 375 mg/m^2 on Day -13
  • Rituxan 1000 mg/m^2 on Days -6, +1, and +8
  • Fludarabine 30 mg/m^2 on Days -5 to -3
  • Cyclophosphamide 750 mg/m^2 on Days -5, -4, -3

Day 0 will be the day of the transplant.

The GVHD prophylaxis will consist of the following:

  • Tacrolimus .09 mg/kg/po (Day -2 thru Day +180). Doses will be adjusted to maintain blood levels of 5-15 ng/mL.
  • Methotrexate 5 mg/m^2 (Days +1, +3, and +6). Unrelated donor recipients will receive a fourth dose on Day +11.

Primary Outcome Measures :
  1. Progression-Free Survival (PFS) [ Time Frame: Year 2 ]
    Patients are considered a failure for this endpoint if they die, or if they relapse/progress or receive anti-lymphoma therapy not including planned post-transplant radiation.

Secondary Outcome Measures :
  1. Graft Failure [ Time Frame: Day 30 ]
    Primary graft failure is defined as a donor peripheral blood T cell chimerism < 5% at Day +30 post-transplant. Secondary Graft Failure is defined as documented engraftment followed by loss of graft as defined by donor peripheral blood T cell chimerism < 5%.

  2. Donor Cell Engraftment [ Time Frame: Days 30 and 100 ]
    Donor engraftment is defined as > 5% donor peripheral blood T cell chimerism by Day +30 post-transplant in the setting of Absolute Neutrophil Count (ANC) recovery (ANC >500/mm^3 for 3 consecutive days).

  3. Time to Neutrophil Recovery [ Time Frame: Day 60 ]
    Neutrophil Recovery is defined as ANC > 500/mm^3 for 3 consecutive days.

  4. Acute Graft-versus-Host Disease (GVHD) [ Time Frame: Day 100 ]
    The event is the incidence of grades II-IV acute GVHD from day of transplant, where grade IV is worst. The first day of acute GVHD onset at a certain grade will be used to calculate a cumulative incidence curve for that acute GVHD grade. GVHD should be monitored in accordance with BMT CTN manual of procedures guidelines. Acute GVHD grading was based on the consensus conference criteria (Przepiorka, et. al., 1994) and the Center for International Blood and Marrow Transplant Research (CIBMTR) grading criteria.

  5. Chronic GVHD [ Time Frame: Year 2 ]
    The event is the incidence and severity of chronic GVHD from day of transplant, a cumulative incidence curve will be computed along with a 95% confidence interval at two years post-transplant. Death prior to occurrence of chronic GVHD will be considered as a competing risk.

  6. Overall Survival [ Time Frame: Years 2 and 3 ]
    The event is death from any cause.

  7. Treatment-related Mortality (TRM) [ Time Frame: Year 3 ]
    The event is death occurring in patients in continuous complete remission. The TRM distribution will be estimated by the Kaplan-Meier curve.

  8. Infections [ Time Frame: Year 2 ]
  9. Quality of Life [ Time Frame: Year 2 ]
  10. Immunologic Reconstitution [ Time Frame: Year 1 ]
    Quantitative immunoglobulins (IgG)

  11. Incidence of Toxicities [ Time Frame: Year 2 ]
    Number of participants that experiences at least one grade 3 - 5 toxicity during the first two years, where grade 5 is worst. Toxicity grades are based on the NCI CTCAE Version 3.0.

  12. Serum Rituximab (RTX) Levels [ Time Frame: Baseline, Days 28 and 365 ]
    RTX concentration levels within participants

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 75 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Must have confirmed CD20+ follicle center lymphoma that meets one of the following:

    1. Histologically confirmed recurrent Revised European American Lymphoma (REAL) Classification CD20+ follicle center lymphoma, follicular grades I and II
    2. Histologically confirmed World Health Organization (WHO) classification CD20+ follicular lymphoma grades 1, 2, or 3a.

      For either classification, the diffuse component of large cleaved cells (if present) cannot be greater than 50% of cellularity. Patients do not have to express t(14;18) to be eligible.

  • Any number of prior regimens (including autologous hematopoietic cell transplantation [HCT]); the most recent prior regimen must have occurred more than 28 days before study entry
  • Must demonstrate chemosensitive or radiosensitive disease to most recent prior regimen and meet one of the following criteria:

    1. Patients in second or subsequent complete remission (CR)
    2. Patients in first or subsequent partial remission (PR)
    3. Patients experiencing a relapse that demonstrates a response, as defined as largest nodal mass less than or equal to 3 cm or greater than or equal to 50% reduction in estimated lymph node volume measured as a product of bi-dimensional measurements (see protocol for detailed definition).
    4. Patients with stable follicular lymphoma are eligible if all lymph node masses are less than or equal to 3 cm and are smaller or unchanged in size to the most recent salvage regimen.
  • Patients with human leukocyte antigen (HLA)-matched donors that meet the following criteria:

    1. 6/6 HLA-matched related donor. HLA typing must be performed by DNA methods for HLA-A and B at intermediate (or higher) resolution, and DRB1 at high resolution. The donor must be willing to donate peripheral blood stem cells and meet institutional criteria for stem cell donation. The donor must be medically eligible to donate stem cells according to individual transplant center criteria; or,
    2. 8/8 HLA-matched unrelated donor. HLA typing must be performed by DNA methods for HLA-A, B, C, and DRB1 at high resolution. The donor must be willing to donate peripheral blood stem cells and meet National Marrow Donor Program (NMDP) criteria for stem cell donation. The donor must be medically eligible to donate stem cells according to NMDP criteria.
  • Patients with adequate organ function, as measured by the following:

    1. Heart: Left ventricular ejection fraction at rest greater than 45%
    2. Lungs: Diffusing capacity of the lung for carbon monoxide (DLCO), forced expiratory volume in one second (FEV1), or forced vital capacity (FVC) greater than 50% of predicted (corrected for hemoglobin). For patients in whom pulse oximetry is performed, baseline O2 saturation greater than 85% (when lung function testing cannot be performed due to age restrictions)
    3. Liver: Bilirubin less than two times the upper limit of normal for age as per local laboratory; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than three times the upper limit of normal as per local laboratory
    4. Kidney: Calculated or measured creatinine clearance greater than or equal to 40 mL/min; if creatinine is greater than or equal to 1.5 mg/dL then 24-hour urine for measured creatinine clearance should be performed.

Exclusion Criteria:

  • Patients in first CR
  • Karnofsky performance score less than 70%
  • Patients with follicular lymphoma that demonstrates evidence of histologic transformation. In the presence of B symptoms, rapid growth of a single dominant site, or prolonged (> 2 yrs) interval since last tissue diagnosis, investigators are encouraged to consider re-biopsy of nodes prior to enrollment.
  • Uncontrolled hypertension
  • Uncontrolled bacterial, viral, or fungal infection (i.e., currently taking medication and progression of clinical symptoms)
  • Prior cancer, other than resected basal cell carcinoma or treated cervical carcinoma in situ. Cancer treated with curative intent less than 5 years will not be allowed unless approved by the medical monitor or protocol chair. Cancer treated with curative intent greater than 5 years will be allowed.
  • Pregnant or breastfeeding
  • Seropositive for human immunodeficiency virus (HIV)
  • Fertile men or women unwilling to use contraception from the time of initiation of conditioning until 6 months post-transplant
  • Prior allogeneic HSCT
  • Known anaphylactic reaction to rituximab
  • Seropositive for any of the following: HIV ab, hepatitis B sAg or polymerase chain reaction (PCR)+, or hepatitis C ab or PCR+

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 identifier (NCT number): NCT00912223

United States, California
City of Hope National Medical Center
Duarte, California, United States, 91010-3000
University of California, San Diego (UCSD) Medical Center
La Jolla, California, United States, 92093
University of California, Davis Medical Center
Sacramento, California, United States, 95817
Stanford Hospital and Clinics
Stanford, California, United States, 94305
United States, Florida
University of Florida College of Medicine
Gainesville, Florida, United States, 32610-0277
H. Lee Moffitt Cancer Center
Tampa, Florida, United States, 33624
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
United States, Massachusetts
Dana-Farber Cancer Institute (DFCI)/Brigham & Women's Hospital
Boston, Massachusetts, United States, 02114
Dana-Farber Cancer Institute (DFCI)/Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Nebraska
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198-7680
United States, North Carolina
University of North Carolina Hospital at Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7305
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
University Hospitals of Cleveland/Case Western
Cleveland, Ohio, United States, 44106-5061
Ohio State/Arthur G. James Cancer Hospital
Columbus, Ohio, United States, 43210
United States, Oklahoma
University of Oklahoma Medical Center
Oklahoma City, Oklahoma, United States, 73104
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232-8210
United States, Texas
University of Texas, MD Anderson Cancer Research Center
Houston, Texas, United States, 77030
United States, West Virginia
West Virginia University
Morgantown, West Virginia, United States, 26506-9162
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792-5156
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53211
Sponsors and Collaborators
Medical College of Wisconsin
National Heart, Lung, and Blood Institute (NHLBI)
Blood and Marrow Transplant Clinical Trials Network
National Cancer Institute (NCI)
National Marrow Donor Program
Study Director: Mary Horowitz, MD, MS Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin

Additional Information:
Publications of Results:
Responsible Party: Medical College of Wisconsin Identifier: NCT00912223     History of Changes
Obsolete Identifiers: NCT00867074
Other Study ID Numbers: BMTCTN0701
U01HL069294 ( U.S. NIH Grant/Contract )
U01HL06929406 ( Other Identifier: National Cancer Institute (NCI) )
5U24CA076518 ( U.S. NIH Grant/Contract )
First Posted: June 3, 2009    Key Record Dates
Results First Posted: November 21, 2016
Last Update Posted: October 27, 2017
Last Verified: February 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Findings will be published in a manuscript.
Time Frame: Within 6 months of official study closure at participating sites.
Access Criteria: Available to the public.

Keywords provided by Medical College of Wisconsin:
Follicular Non-Hodgkin's Lymphoma
Hematopoietic Stem Cell Transplant (HSCT)
Non-Myeloablative Transplant (NST)

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Lymphoma, Follicular
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases