Clinical Trial: Autologous Peripheral Blood Stem Cell Transplant Followed by Donor Bone Marrow Transplant in Treating Patients With High-Risk Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Multiple Myeloma, or Chronic Lymphocytic Leukemia

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Sequential Autologous HCT / Nonmyeloablative Allogeneic HCT Using Related, HLA-Haploidentical Donors for Patients With High-Risk Lymphoma, Multiple Myeloma, or Chronic Lymphocytic Leukemia

Brief Summary: This phase II trial studies autologous peripheral blood stem cell transplant followed by donor bone marrow transplant in treating patients with high-risk Hodgkin lymphoma, non-Hodgkin lymphoma, multiple myeloma, or chronic lymphocytic leukemia. Autologous stem cell transplantation uses the patient's stem cells and does not cause graft versus host disease (GVHD) and has a very low risk of death, while minimizing the number of cancer cells. Peripheral blood stem cell (PBSC) transplant uses stem cells from the patient or a donor and may be able to replace immune cells that were destroyed by chemotherapy. These donated stem cells may help destroy cancer cells. Bone marrow transplant known as a nonmyeloablative transplant uses stem cells from a haploidentical family donor. Autologous peripheral blood stem cell transplant followed by donor bone marrow transplant may work better in treating patients with high-risk Hodgkin lymphoma, non-Hodgkin lymphoma, multiple myeloma, or chronic lymphocytic leukemia.

Detailed Summary:

PRIMARY OBJECTIVES:

I. Event-free survival (EFS) at 1-year after autograft.

SECONDARY OBJECTIVES:

I. Relapse rates at 1-year after autograft.

II. Overall survival (OS) at 1-year after autograft.

III. Incidence of grades II-IV acute GVHD and chronic extensive GVHD.

IV. Non-relapse mortality (NRM) at 200 days and 1 year after allograft.

V. Donor engraftment at day +84.

VI. Incidence of infections.

OUTLINE:

CONDITIONING REGIMEN 1 (lymphoma, Waldenstrom macroglobulinemia, or chronic lymphocytic leukemia [CLL] with no dose limiting radiation or significant comorbidities: Patients receive cyclophosphamide intravenously (IV) on days -6 and -5. Patients undergo high-dose total body irradiation (TBI) twice daily (BID) on days -3 to -1.

CONDITIONING REGIMEN 2 (lymphoma, Waldenstrom Macroglobulinemia, CLL, with prior dose-limiting radiation, or significant comorbidities): Patients receive carmustine IV on day -7, etoposide IV BID on days -6 to -3, cytarabine IV BID on days -6 to -3, and melphalan IV on day -2.

CONDITIONING REGIMEN 3 (multiple myeloma or plasma cell leukemia, with no significant renal insufficiency or other significant comorbidities): Patients receive high-dose melphalan IV on day -2.

CONDITIONING REGIMEN 4 (multiple myeloma or plasma cell leukemia, with significant renal insuff
Sponsor: Fred Hutchinson Cancer Research Center

Current Primary Outcome: Progression-free survival (PFS) [ Time Frame: From the date of autologous transplant until the time of death, assessed up to 1 year ]

Original Primary Outcome: Progression-free survival [ Time Frame: 1-year post-transplant ]

Current Secondary Outcome:

• Early non-relapse mortality (NRM) [ Time Frame: At 200 days ]
  Recorded and reported on clinical reporting forms. Every effort will be made to determine the exact cause of death for all patients as they occur. Reasonable evidence will be taken to mean that the lower bound of a one-sided 80% confidence interval for the true rate of NRM is above 0.30.
• Early NRM [ Time Frame: At 1 year ]
  Recorded and reported on clinical reporting forms. Every effort will be made to determine the exact cause of death for all patients as they occur. Reasonable evidence will be taken to mean that the lower bound of a one-sided 80% confidence interval for the true rate of NRM is above 0.30.
• Immune reconstitution after allografting [ Time Frame: Up to 1 year ]
• Incidence of acute and chronic GVHD [ Time Frame: Up to 84 days ]
  Skin involvement should be assessed by punch biopsy. The percentage of body surface area involved will be recorded. Gastrointestinal symptoms suspicious for GVHD should be evaluated by endoscopy and biopsy as indicated. Time to onset of GVHD will be recorded.
• Incidence of engraftment failure or rejection [ Time Frame: Up to 1 year ]
• Incidence of infections [ Time Frame: Up to 1 year ]
• Overall survival [ Time Frame: At 1 year ]
  Estimated by the method of Kaplan and Meier. Confidence intervals will also be estimated.
• Rates of relapse, defined by presence of malignant cells in marrow, peripheral blood or extramedullary sites detectable by morphologic, flow cytometric, cytogenetic or molecular assays not evident at the time of transplant [ Time Frame: At 1 year ]
  Summarized using cumulative incidence estimates. Confidence intervals will also be estimated.
• Reconstitution of lymphocyte subsets in peripheral blood [ Time Frame: Up to 84 days ]
  Absolute counts of B-cells (CD19+), T-cell subsets (determined by differential expression of CD4, CD8 or CD45 isoforms on CD3+ cells) and natural killer cells (CD16+/CD56+) in peripheral blood should be compared to pre-transplant lymphocyte.
• Severity of acute and chronic GVHD [ Time Frame: Up to 84 days ]
  Skin involvement should be assessed by punch biopsy. The percentage of body surface area involved will be recorded. Gastrointestinal symptoms suspicious for GVHD should be evaluated by endoscopy and biopsy as indicated. Time to onset of GVHD will be recorded.

Original Secondary Outcome:

• Rates of relapse [ Time Frame: 1-year post-transplant ]
• Early non-relapse mortality [ Time Frame: 200-days post-transplant ]
• Incidence/severity of acute graft-versus-host disease [ Time Frame: 120-days post-transplant ]
• Toxicities and infections [ Time Frame: 1-year post-transplant ]

Information By: Fred Hutchinson Cancer Research Center

Dates:
Date Received: November 4, 2009
Date Started: March 2010
Date Completion:
Last Updated: January 6, 2017
Last Verified: January 2017