Clinical trial NCT00612716: Donor Stem Cell Transplant in Treating Patients With Previously Treated Lymphoma, Multiple Myeloma, or Chronic Lymphocytic Leukemia
Official title: Unrelated or Partially Matched Allogeneic Donor Stem Cells for Lymphoma, Myeloma, and Chronic Lymphocytic Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Keywords: stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
refractory multiple myeloma
recurrent adult Hodgkin lymphoma
recurrent/refractory childhood Hodgkin lymphoma
refractory chronic lymphocytic leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
recurrent adult grade III lymphomatoid granulomatosis
adult nasal type extranodal NK/T-cell lymphoma
Waldenstrom macroglobulinemia
recurrent adult Burkitt lymphoma
stage I adult Burkitt lymphoma
stage II adult Burkitt lymphoma
stage III adult Burkitt lymphoma
stage IV adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult immunoblastic large cell lymphoma
stage I adult immunoblastic large cell lymphoma
stage II adult immunoblastic large cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
stage I adult lymphoblastic lymphoma
stage II adult lymphoblastic lymphoma
stage III adult lymphoblastic lymphoma
stage IV adult lymphoblastic lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent mantle cell lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
recurrent marginal zone lymphoma
splenic marginal zone lymphoma
recurrent small lymphocytic lymphoma
recurrent childhood anaplastic large cell lymphoma
recurrent childhood grade III lymphomatoid granulomatosis
childhood diffuse large cell lymphoma
childhood immunoblastic large cell lymphoma
recurrent childhood large cell lymphoma
recurrent childhood lymphoblastic lymphoma
childhood nasal type extranodal NK/T-cell lymphoma
Burkitt lymphoma
recurrent childhood small noncleaved cell lymphoma
stage I childhood small noncleaved cell lymphoma
stage II childhood small noncleaved cell lymphoma
stage III childhood small noncleaved cell lymphoma
stage IV childhood small noncleaved cell lymphoma
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2008-02-12
Enrollment: 6
Sex: ALL
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Giving chemotherapy, such as cyclophosphamide and busulfan, and total-body irradiation before a donor stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells from bone marrow or umbilical cord blood may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving methotrexate and cyclosporine after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well a donor stem cell transplant works in treating patients with previously treated lymphoma, multiple myeloma, or chronic lymphocytic leukemia.

Detailed description: OBJECTIVES:

* Determine if allogeneic stem cell transplantation using unrelated matched or related haploidentical donor bone marrow or unrelated matched cord blood results in timely, complete, and durable engraftment in patients with previously treated lymphoma, multiple myeloma, or chronic lymphocytic leukemia.
* Determine the incidence and grade of acute and chronic graft-versus-host disease in patients treated with this regimen.
* Determine if the augmented graft-versus-tumor effect accompanying unrelated or partially matched donor allogeneic transplant reduces the incidence of relapse in these patients.

OUTLINE:

* Preparative regimen: Patients receive cyclophosphamide IV over 2 hours on days -7 and -6 and undergo total-body irradiation (TBI) twice daily on days -4 to -1. Patients who are unable to undergo TBI receive busulfan IV or orally 4 times daily on days -9 to -6 and cyclophosphamide IV over 2 hours on days -5 to -2.
* Stem cell transplantation: All patients undergo unrelated matched bone marrow or umbilical cord blood transplantation or partially matched related allogeneic bone marrow transplantation on day 0.
* Graft-versus-host disease (GVHD) prophylaxis: Patients receive GVHD prophylaxis comprising methotrexate and cyclosporine. Patients may be enrolled in other protocols directed towards GVHD prophylaxis.

Eligibility criteria: Inclusion Criteria:

* Donors will be \<55 years of age and in good health as approved by the National Marrow Donor Program (NMDP) donor and collection centers. Related donors will be \< 70 years of age.
* Recipients will be \<55 years, will have satisfactory organ function (excluding bone marrow) and will have a Karnofsky activity assessment \>90% and will have:

  * Creatinine \<2.0 mg/dl.
  * Bilirubin, Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<2 x normal.
  * Pulmonary function test and Carbon Monoxide Diffusing Capacity (DLCO) \> 50% of normal.
  * Multi Gated Acquisition Scan (MUGA) \>45% injection fraction.
* Recipients with unrelated donor matched at the HLA A, B, DRBI loci, or if \< 35 years mismatched at a single HLA A or B, or DRBI locus.
* Umbilical cord blood (5) used as an unrelated stem cell source will provide \> 2.0 x 10\^7 cells/kg and will be matched at 4 - 6 of 6 HLA A, B, and DRBI loci. Cord blood grafts may include a single or pair of cord units depending on the cell dose.
* Partially matched related donors will be at least haploidentical (matched at \>3 of 6 HLA A, B, DRB1 loci).
* Recipients will fall under one of the following disease categories

  * Chronic lymphocytic leukemia -- must have all three:

    * Rai Stage III/IV
    * Progression after previous Complete Response (CR) or Partial Response (PR) including purine antagonist (i.e. fludarabine).
    * Recent chemotherapy responsiveness
  * Advanced non-Hodgkin's lymphoma(NHL).

    * Low-grade NHL (Working Formulation A, B, C) following progression after initial therapy if asymptomatic at diagnosis (\>CR2, \>PR2; response duration \< 1 year from last therapy) or if no CR was achieved (\>PR1). At least one prior therapy of intermediate intensity (e.g. CHOP).
    * Mantle zone lymphoma after any progression following initial therapy (\>CR1, \> PR1). At least one prior therapy of intermediate intensity (e.g. CHOP).
    * Intermediate grade lymphoma (\>PR2). Response duration \<1 year from prior therapy.
    * High-grade Non-Hodgkin's Lymphoma (NHL) (IWF H, I, J) after initial therapy if \>stage III at diagnosis; after any progression even if localized (stage I, II) at diagnosis with prior response duration \< 1 year.
    * Recent chemotherapy responsiveness after treatment with \> 3 intermediate intensity regimens.
  * Advanced Hodgkin's disease beyond PR2 (\>CR3, \>PR3).

    * Recent chemotherapy responsiveness
  * Multiple Myeloma (\>CR2, \>PR2) or after initial therapy if no prior PR.

    * Recent chemotherapy responsiveness
* Recipients will sign informed consent approved by the Committee on the Use of Human Subjects at the University of Minnesota.

Exclusion Criteria:

* No available histocompatible related donor; 2nd bone marrow transplant (BMT), HIV-1 positive; active uncontrolled infection; or resistant malignancy.

Primary outcomes:
measure: Number of Participants With Engraftment Failure
timeFrame: 3 Months
measure: Number of Participants With Neutrophil Engraftment
timeFrame: Day 42
measure: Number of Participants With Platelet Engraftment
timeFrame: Day 180
measure: Number of Participants With Grade 3-4 Acute Graft-versus-host Disease
timeFrame: Day 100
measure: Number of Participants With Persistence Disease
timeFrame: 3 Years
measure: Number of Participants With Relapse of Malignancy
timeFrame: 3 Years
measure: Number of Participants With 1 Year Overall Survival
timeFrame: 1 year
measure: Number of Participants With 2 Year Overall Survival
timeFrame: 2 year
Secondary outcomes:
measure: Number of Participants With of Chronic GVHD.
timeFrame: 1 Year
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Masonic Cancer Center, University of Minnesota
state: Minnesota
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Daniel J. Weisdorf, MD
role: PRINCIPAL_INVESTIGATOR
References: