Combination Chemotherapy Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or High-Risk Primary Refractory Hodgkin Lymphoma
Condition: Lymphoma
MeSH terms: Lymphoma; Hodgkin Disease
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Giving chemotherapy before a donor stem cell transplant helps stop the growth of
      cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem
      cells. When the healthy stem cells from a donor are infused into the patient they may help
      the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.
      Sometimes the transplanted cells from a donor can make an immune response against the body's
      normal cells. Giving cyclosporine, mycophenolate mofetil, and methotrexate before and after
      transplant may stop this from happening.

      PURPOSE: This phase II trial is studying how well combination chemotherapy followed by donor
      stem cell transplant works in treating patients with relapsed or high-risk primary refractory
      Hodgkin lymphoma.
    

Detailed description: 
      OUTLINE: Patients are stratified according to response to prior therapy and risk factors
      (those with presence of all 3 risk factors and failed primary therapy or primary progressive
      disease vs. patients who relapse more than 100 days after an autologous stem cell
      transplant).

        -  Salvage chemotherapy (IGV or MOPP): Patients who have previously received
           mechlorethamine hydrochloride receive IGV; patients who have previously received a
           gemcitabine-based regimen receive MOPP.

             -  IGV (ifosfamide, gemcitabine hydrochloride, and vinorelbine ditartrate): Patients
                receive IGV combination chemotherapy comprising ifosfamide IV on days 1-4,
                gemcitabine hydrochloride IV on days 1 and 4, and vinorelbine ditartrate IV on day
                1. Treatment repeats every 2-3 weeks for 2-3 courses in the absence of disease
                progression or unacceptable toxicity.

             -  MOPP (mechlorethamine hydrochloride, vincristine, procarbazine hydrochloride, and
                prednisone): Patients receive MOPP combination chemotherapy comprising
                mechlorethamine hydrochloride IV on days 1 and 8, vincristine IV on days 1 and 8,
                oral procarbazine hydrochloride on days 1-14, and oral prednisone on days 1-14.
                Treatment repeats every 4 weeks for at least 2 courses in the absence of disease
                progression or unacceptable toxicity.

      Patients with no progression of disease after salvage chemotherapy (at allograft work-up)
      proceed to allogeneic hematopoietic stem cell transplantation [AHSCT]* within 60 days after
      completion of salvage chemotherapy.

      NOTE: *Patients with a nodal mass > 5 cm that has not ben previously irradiated and in the
      absence of extranodal disease may undergo involved-field radiotherapy twice daily for 2
      weeks, prior to AHSCT.

        -  AHSCT with reduced-intensity or non-myeloablative conditioning: Patients achieving
           partial response or stable disease after salvage therapy receive fludarabine phosphate
           IV over 30 minutes on days -6 to -2; melphalan IV over 15 minutes on days -6 and -5; and
           undergo AHSCT on day 0 (reduced-intensity conditioning). Patients achieving complete
           response after salvage therapy receive fludarabine phosphate IV over 30 minutes on days
           -6 to -2; cyclophosphamide IV over 15 minutes on day -6; total-body irradiation over
           20-30 minutes on day -1; and undergo AHSCT on day 0 (non-myeloablative conditioning).

        -  Graft-vs-host disease prophylaxis: Patients with related or unrelated donors receive
           cyclosporine IV over 2-4 hours or orally on days -3 to 100 followed by a taper,
           mycophenolate mofetil IV or orally on days -3 to 46 followed by a taper, and
           methotrexate IV on days 1, 3, 6, and 11.

      Patients who received umbilical cord blood receive cyclosporine and mycophenolate mofetil as
      above (no methotrexate).

      Follow-up period of 2 years post-transplant.
    

Intervention name(s): cyclophosphamide; cyclosporine; fludarabine phosphate; gemcitabine hydrochloride; ifosfamide; mechlorethamine hydrochloride; melphalan; methotrexate; mycophenolate mofetil; prednisone; procarbazine hydrochloride; vincristine sulfate; vinorelbine tartrate; allogeneic bone marrow transplantation; allogeneic hematopoietic stem cell transplantation; nonmyeloablative allogeneic hematopoietic stem cell transplantation; peripheral blood stem cell transplantation; umbilical cord blood transplantation; total-body irradiation
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Procedure; Procedure; Procedure; Procedure; Procedure; Radiation
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Prednisone; Cyclophosphamide; Melphalan; Ifosfamide; Mechlorethamine; Gemcitabine; Methotrexate; Fludarabine; Fludarabine phosphate; Vincristine; Vinorelbine; Procarbazine; Cyclosporins
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: recurrent adult Hodgkin lymphoma; recurrent/refractory childhood Hodgkin lymphoma; adult lymphocyte depletion Hodgkin lymphoma; adult nodular sclerosis Hodgkin lymphoma; adult mixed cellularity Hodgkin lymphoma; childhood lymphocyte depletion Hodgkin lymphoma; childhood mixed cellularity Hodgkin lymphoma; childhood nodular sclerosis Hodgkin lymphoma; stage III adult Hodgkin lymphoma; stage IV adult Hodgkin lymphoma; stage III childhood Hodgkin lymphoma; stage IV childhood Hodgkin lymphoma