Autologous Followed by Non-myeloablative Allogeneic Transplantation for Non-Hodgkin's Lymphoma
Condition: Lymphoma, Non-Hodgkin
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin
Intervention: Cyclophosphamide; BCNU; Etoposide; Filgrastim; Antithymocyte globulin; Cyclosporine; Mycophenolate mofetil; Rituximab; Autologous hematopoietic stem cell transplantation (auto-HSCT); Allogeneic hematopoietic stem cell transplantation (allo-HSCT); Total lymphoid irradiation; CD34+ Cells; Solu-Medrol
Intervention description: 4 gm /m² IV over 2 hours on day 8; The dose of BCNU will be based on actual body weight unless the actual body weight is more than 15 kg greater than the ideal body weight in which case the adjusted ideal body weight will be used:
Males IBW = 50 kg + 2.3 kg/inch over 5 feet Females IBW = 45.5 kg + 2.3 kg/inch over 5 feet Adjusted IBW = IBW + 50% (actual weight - IBW); 60mg/kg, IV over 4 hours on day -4 pre-transplant and for preparative regimen. The dose of etoposide for mobilization is 2 gm/ m².; 10µg/kg sc qd starting day following cyclosphamide (or VP-16) until last day of apheresis; 1.5 mg/kg/d, IV from day -11 to -7; 5mg/kgbid,variable, po or IV; 15 mg/kg po on day 0, at 5-10 hours after mobilized PBPC infusion is complete. Thereafter, beginning on day +1 MMF is taken at 15 mg/kg po b.i.d. (30 mg/kg/day) if transplantation was using a matched related donor and 15 mg/kg po t.i.d if from a matched unrelated donor or a one antigen mismatched donor. Doses will be rounded up to the nearest 250 mg (capsules are 250 mg). MMF will be stopped on day +28 for matched related donors. For one antigen mismatched related or unrelated donors, the taper will begin on day +40. MMF will be tapered by 10% weekly till off, typically by day +96. If there is nausea and vomiting at any time preventing the oral administration of MMF, MMF should be administered intravenously at an equal dose. MMF dosing is based on actual body weight.; 375 mg/m2 IV (calculated based on actual body weight) on day 1 and day 7. Administered per current standard of care..; Auto-HCT involves an intravenous infusion of a participant's previously collected and frozen white blood cells collected after treatment with mobilizing agents; Allo-HCT involves an intravenous infusion of a donor's white blood cells collected after treatment with mobilization with filgrastim (G-CSF); TLI is administered in 80cGy fractions on Days -11 to Day-7 relative to allo-HSCT; 2 x 10e6 CD34+ cells per kg actual body weight on Day 0; 1 mg/kg, Day-11 to Day-7
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Cyclophosphamide; Carmustine; Rituximab; Etoposide; Cyclosporins; Antilymphocyte Serum; Lenograstim; Prednisolone hemisuccinate; Prednisolone phosphate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      The purpose of this trial is to develop an alternative treatment for patients with poor risk
      non-Hodgkin's lymphoma. This trial uses a combination of high dose chemotherapy with stem
      cell transplant using the patient's own cells. This is followed with non-myeloablative
      transplant using stem cells from a related or unrelated donor to try and generate an
      anti-lymphoma response from the new immune system.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age 18 to 70 years.

          -  Histologically proven non-Hodgkin's lymphoma

          -  Relapse after achieving initial remission or failure to achieve initial remission.

          -  KPS > 70%

          -  Matched related or unrelated donor identified and available. Donor must be a complete
             match or have only a single allele mismatch.

          -  Recent Bone marrow biopsy and cytogenetic analysis

          -  Patients must have a pretreatment serum bilirubin < 2 x the institutional ULN, a serum
             creatinine < 2 x the institutional ULN and measured or estimated creatinine clearance
             > 50 cc/min by the following formula (all tests must be performed within 28 days prior
             to mobilization ): Estimated Creatinine Clearance = (140 age) X WT(kg) X 0.85 if
             female 72 X serum creatinine(mg/dl).

          -  Patients must have an EKG within 42 days prior to registration that shows no
             significant abnormalities that are suggestive of active cardiac disease.

          -  Patients must have an echocardiogram or MUGA scan within 42 days of registration. If
             the ejection fraction is < 40%, the patient will not be eligible. If the ejection
             fraction is 40-50%, patients must have an exercise echocardiogram or dobutamine-echo
             with a normal response to exercise.

          -  Patients must have a corrected diffusion capacity > 50% prior to the autologous
             transplant and > 40% prior to the allogeneic transplant.

          -  Patients with known allergy to etoposide or a history of Grade 3 hemorrhagic cystitis
             with cyclophosphamide are not eligible.

          -  Patients must be informed of the investigational nature of this study and must sign
             and give written informed consent in accordance with institutional and federal
             guidelines.

        Exclusion Criteria:

          -  Pregnant or breast-feeding women are ineligible due to the known birth defects
             association with the treatments used in this study.

          -  Patients known to be human immunodeficiency virus (HIV)-positive are ineligible
             because the concern for opportunistic infection and hematologic reserve are considered
             to be significantly greater in this population.

          -  Patients with prior maligancies diagnosed > 5 years ago without evidence of disease
             are eligible. Patients with a prior malignancy treated < 5 years ago but have a life
             expectancy of > 5 years for that malignancy are eligible.

          -  Patients with uncontrolled infection.

          -  No prior autologous or allogeneic hematopoietic cell transplantation.

        Donor Selection/Evaluation:

          -  Related or unrelated HLA identical donors who are in good health and have no
             contra-indication to donation.

          -  No contra-indication for the donor to collection by apheresis of mononuclear cells
             mobilized by G-CSF at a dose of 16 µg/kg of body weight.

          -  Virology testing including CMV, HIV, EBV, HTLV, RPR, Hepatitis A, B and C will be
             performed within 30 days of donation.

          -  No prior malignancy is allowed except adequately treated basal cell or squamous cell
             skin cancer, in situ cervical cancer or other cancer for which the donor has been
             disease-free for five years