Allogeneic Blood Stem Cell Transplantation and Adoptive Immunotherapy for Hodgkin's Disease
Condition: Hodgkin's Disease
MeSH terms: Hodgkin Disease
Intervention: Gemcitabine; Fludarabine; Melphalan; Antithymocyte Globulin; Allogeneic Stem Cell Infusion; Tacrolimus; Filgrastim (G-CSF); Methotrexate
Intervention description: 800 mg/m^2 IV over 30 minutes on Day -7 (1 day); 33 mg/m^2 IV over 30 minutes Day -5 to Day -2 (4 days); 70 mg/m^2 IV over 30 minutes on Day -3 to Day -2 (2 days); 2 mg/kg IV on Day -4 and Day -3 (2 days) before stem cell transplantation.
If receiving transplant from matched unrelated donor (not a blood relative), a mismatched related donor (a blood relative, but not a full match), or receiving a cord blood transplant.; Infusion of stem cells on Day 0.; 0.03 mg/kg beginning Day -2 by vein over 24 hours; when tolerable change to pill form given once daily for 3-4 months.; Starting 1 week after transplant (Day +7) given as injection under the skin once daily until blood cell levels return to normal.; 5 mg/m2 by vein on Days +1, +3, +6, and +11 to decrease risk of GVHD.
Intervention MeSH terms: Gemcitabine; Methotrexate; Fludarabine phosphate; Fludarabine; Melphalan; Tacrolimus; Thymoglobulin; Antilymphocyte Serum
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 52.0
Sex: All
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Hodgkin's Disease; Stem Cell Transplantation; Antithymocyte Globulin; Gemcitabine; Gemzar; Fludarabine; Fludarabine Phosphate; Melphalan; Allogeneic stem cell transplantation; AST; SCT; ATG; Thymoglobulin

Summary:

      The goal of this clinical research study is to learn if fludarabine, melphalan and
      gemcitabine followed by transplantation of stem cells (blood-forming cells) as well as immune
      cells (lymphocytes), collected from a matched related (i.e. a sibling) or unrelated donor, or
      a mismatched related donor, can help to control Hodgkin's disease. The safety of the
      treatment will also be studied.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients < 65 years of age with histologically confirmed refractory or relapsed
             Hodgkin's disease (including patients who fail or relapse after autologous SCT). This
             upper age limit will apply to transplants from both matched related and unrelated
             donors.

          2. Patients should have any of the following disease status: a. responsive or stable
             disease on salvage chemotherapy or radiation therapy. b. untreated, smoldering (i.e.
             not rapidly progressive) relapses.

          3. Patients must have a serum bilirubin equal to or </=2.0 mg/dl (isolated
             hyperbilirubinemia related to Gilbert's disease allowed), serum transaminase (ALT)
             equal to or </= 3 times the upper limit of the normal range, serum creatinine <2.0
             mg/dl (provided they also have a glomerular filtration rate of at least 55 ml/min), no
             symptomatic cardiac or pulmonary disease and a performance status equal to or </=2.
             Left ventricular ejection fraction >/= 40%, forced expiratory volume at one second
             (FEV1), forced vital capacity (FVC) and corrected diffusing capacity of lung for
             carbon monoxide (DLCO) >/= 50% predicted.

          4. Patients must have an HLA-compatible related or unrelated donor (one-antigen
             mismatched related donors are acceptable) willing to donate marrow or
             rhG-CSF-mobilized peripheral blood stem cells. In the event of transplants from
             matched unrelated donors, a high-resolution allele match for HLA-A, -B, -C, -DRB1 ("8
             of 8 match") is required.

          5. Women of childbearing potential must have a negative serum pregnancy test within two
             weeks of study entry and should be advised to avoid becoming pregnant. Men should be
             advised to not father a child while on treatment. Both women of childbearing potential
             and men must agree to practice effective methods of contraception.

          6. Patients must be capable and willing to sign informed consent.

        Exclusion Criteria:

          1. Patients with documented disease progression on salvage chemotherapy.

          2. Nursing or pregnant females. Should a woman become pregnant or suspect she is pregnant
             while participating in the study, she should inform her treating physician
             immediately.

          3. Severe concomitant medical or psychiatric illness.

          4. Uncontrolled arrhythmia or symptomatic cardiac or pulmonary disease.

          5. Chronic active hepatitis or cirrhosis.

          6. Active or uncontrolled infection.

          7. Radiation therapy involving chest (axilla excluded), mediastinum, or abdomen (i.e.,
             small or large bowel) completed within 10 weeks of transplant admission. Radiation
             therapy shortly before the start of the preparative regimen is allowed.

          8. Prior or concurrent malignancies (including myelodysplasia) except resected basal cell
             carcinoma or treated carcinoma in-situ. Cancer treated with curative intent < 5 years
             previously will not be allowed unless approved by the Protocol Chair. Cancer treated
             with curative intent > 5 years previously will be allowed.