Blood Stem Cell Transplant With Low Dose Chemotherapy for Relapsed Follicular Non-Hodgkin's Lymphoma (BMT CTN 0701)
Condition: Lymphoma, Non-Hodgkin
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, Follicular
Intervention: Hematopoietic Stem Cell Transplant
Intervention description: 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.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 65.0
Sex: All
Minimum age: 1 Year
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Follicular Non-Hodgkin's Lymphoma; Hematopoietic Stem Cell Transplant (HSCT); Non-Myeloablative Transplant (NST)

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).
    

Eligibility criteria:

        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+