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Lymphoma, Non-HodgkinPhase 2NCT00912223

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

A Phase 2 study testing Hematopoietic Stem Cell Transplant in people with Lymphoma, Non-Hodgkin, run by Medical College of Wisconsin at 21 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 1 year to 75 years
Conditions the study is for
Lymphoma, Non-Hodgkin
What is being tested?
Hematopoietic Stem Cell Transplant
Could I receive a placebo?
No, everyone receives an active treatment
How many people
65 participants
Where
21 sitesUnited States
Study dates
Apr 2009to Aug 2016
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year to 75 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Must have confirmed CD20+ follicle center lymphoma that meets one of the following:
  • Histologically confirmed recurrent Revised European American Lymphoma (REAL) Classification CD20+ follicle center lymphoma, follicular grades I and II
  • 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:
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  • Patients in second or subsequent complete remission (CR)
  • Patients in first or subsequent partial remission (PR)
  • 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).
  • 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:
  • 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,
  • 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:
  • Heart: Left ventricular ejection fraction at rest greater than 45%
  • 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)
  • 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
  • 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.

Who cannot join

  • 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.
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  • 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+

Trial locations and contacts

21 sites in 1 country.

21 sites in 1 country

United States21 sites

  • Dana-Farber Cancer Institute (DFCI)/Brigham & Women's Hospital

    Boston, Massachusetts, 02114

  • Dana-Farber Cancer Institute (DFCI)/Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • University of North Carolina Hospital at Chapel Hill

    Chapel Hill, North Carolina, 27599-7305

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • University Hospitals of Cleveland/Case Western

    Cleveland, Ohio, 44106-5061

  • Ohio State/Arthur G. James Cancer Hospital

    Columbus, Ohio, 43210

  • City of Hope National Medical Center

    Duarte, California, 91010-3000

  • University of Florida College of Medicine

    Gainesville, Florida, 32610-0277

  • University of Texas, MD Anderson Cancer Research Center

    Houston, Texas, 77030

  • University of California, San Diego (UCSD) Medical Center

    La Jolla, California, 92093

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792-5156

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53211

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • West Virginia University

    Morgantown, West Virginia, 26506-9162

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232-8210

  • University of Oklahoma Medical Center

    Oklahoma City, Oklahoma, 73104

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198-7680

  • University of California, Davis Medical Center

    Sacramento, California, 95817

  • Stanford Hospital and Clinics

    Stanford, California, 94305

  • H. Lee Moffitt Cancer Center

    Tampa, Florida, 33624

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

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)

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).

Read the 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.

Being tested
Hematopoietic Stem Cell Transplant
Keywords
Follicular Non-Hodgkin's Lymphoma, Hematopoietic Stem Cell Transplant (HSCT), Non-Myeloablative Transplant (NST)
Medical subject headings
Lymphoma, Non-Hodgkin, Lymphoma, Follicular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Hematopoietic Stem Cell TransplantBiological

    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.
Study groups in NCT00912223
Study groupRoleWhat they receive
Hematopoietic Stem Cell TransplantExperimentalParticipants will undergo a non-myeloablative allogeneic hematopoietic stem cell transplant.
Receives: Biological: Hematopoietic Stem Cell Transplant

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-Free Survival (PFS)

    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.

    Measured: Year 2

Secondary outcomes (12)

  1. Graft Failure

    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%.

    Measured: Day 30

  2. Donor Cell Engraftment

    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).

    Measured: Days 30 and 100

  3. Time to Neutrophil Recovery

    Neutrophil Recovery is defined as ANC > 500/mm^3 for 3 consecutive days.

    Measured: Day 60

  4. Acute Graft-versus-Host Disease (GVHD)

    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.

    Measured: Day 100

  5. Chronic GVHD

    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.

    Measured: Year 2

  6. Overall Survival

    The event is death from any cause.

    Measured: Years 2 and 3

  7. Treatment-related Mortality (TRM)

    The event is death occurring in patients in continuous complete remission. The TRM distribution will be estimated by the Kaplan-Meier curve.

    Measured: Year 3

  8. Infections

    Measured: Year 2

  9. Quality of Life

    Measured: Year 2

  10. Immunologic Reconstitution

    Quantitative immunoglobulins (IgG)

    Measured: Year 1

  11. Incidence of Toxicities

    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.

    Measured: Year 2

  12. Serum Rituximab (RTX) Levels

    RTX concentration levels within participants

    Measured: Baseline, Days 28 and 365

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Jun 2009 (estimated)
  2. Study startApr 2009
  3. Primary completionNov 2014
  4. Study completionAug 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
65 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00912223
Sponsor's protocol ID
BMTCTN0701
Other IDs
U01HL069294, U01HL06929406, 5U24CA076518
Status last verified
Dec 2022
First submitted
1 Jun 2009
Last updated
9 Dec 2022
Data monitoring committee
Yes
Individual data sharing
Yes: Findings will be published in a manuscript.

Publications

  • Laport GG, Wu J, Logan B, Bachanova V, Hosing C, Fenske T, Longo W, Devine SM, Nademanee A, Gersten I, Horowitz M, Lazarus HM, Riches ML; Blood and Marrow Transplant Clinical Trials Network. Reduced-Intensity Conditioning with Fludarabine, Cyclophosphamide, and High-Dose Rituximab for Allogeneic Hematopoietic Cell Transplantation for Follicular Lymphoma: A Phase Two Multicenter Trial from the Blood and Marrow Transplant Clinical Trials Network. Biol Blood Marrow Transplant. 2016 Aug;22(8):1440-1448. doi: 10.1016/j.bbmt.2016.04.014. Epub 2016 Apr 23.

    PubMed 27118571

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Hematopoietic Stem Cell Transplant in people with Lymphoma, Non-Hodgkin, run by Medical College of Wisconsin at 21 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Nov 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-Free Survival (PFS) (time frame: Year 2). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00912223, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2022.

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