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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Fred Hutchinson Cancer Research Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT01008462
First received: November 4, 2009
Last updated: June 10, 2014
Last verified: June 2014
  Purpose

This study was designed to combine two types of stem cell transplant. The first would be the use of high-dose chemotherapy and autologous stem cell transplantation (using your own stem cells). This type of stem cell transplant has the advantage of no graft-versus-host disease (GVHD) and very low risk of death, while minimizing the number of cancer cells. Then, the investigators will wait for a period between 40-120 days to allow your body to recover from the high-dose chemotherapy. Then, you will receive the second type of transplant "nonmyeloablative transplant" from your haploidentical family donor. The investigators hope that the donor cells will then eliminate any remaining tumor cells.

The investigators are doing this study:

  • To see if the combined stem cell transplant will help prevent the blood or lymph nodes' cancer from coming back.
  • To see if the combined stem cell transplant will be safe with no increased toxicities or deaths compared to "nonmyeloablative transplant" alone.

Peripheral blood stem cell (PBSC) transplant using stem cells from the patient or a donor may be able to replace immune cells that were destroyed by chemotherapy used to kill cancer cells. These donated stem cells may help destroy cancer cells (graft-versus-tumor effect).


Condition Intervention Phase
Adult Nasal Type Extranodal NK/T-cell Lymphoma
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-cell Lymphoma
B-cell Chronic Lymphocytic Leukemia
Childhood Burkitt Lymphoma
Childhood Diffuse Large Cell Lymphoma
Childhood Immunoblastic Large Cell Lymphoma
Childhood Nasal Type Extranodal NK/T-cell Lymphoma
Cutaneous B-cell Non-Hodgkin Lymphoma
Peripheral T-cell Lymphoma
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Adult Grade III Lymphomatoid Granulomatosis
Recurrent Adult Hodgkin Lymphoma
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Childhood Anaplastic Large Cell Lymphoma
Recurrent Childhood Grade III Lymphomatoid Granulomatosis
Recurrent Childhood Large Cell Lymphoma
Recurrent Childhood Lymphoblastic Lymphoma
Recurrent Childhood Small Noncleaved Cell Lymphoma
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Mycosis Fungoides/Sezary Syndrome
Recurrent Small Lymphocytic Lymphoma
Recurrent/Refractory Childhood Hodgkin Lymphoma
Refractory Chronic Lymphocytic Leukemia
Refractory Multiple Myeloma
Splenic Marginal Zone Lymphoma
Waldenström Macroglobulinemia
Drug: carmustine
Drug: etoposide
Drug: cytarabine
Drug: fludarabine phosphate
Drug: cyclophosphamide
Drug: tacrolimus
Drug: mycophenolate mofetil
Radiation: total-body irradiation
Drug: melphalan
Procedure: autologous-allogeneic tandem hematopoietic stem cell transplantation
Procedure: autologous hematopoietic stem cell transplantation
Procedure: allogeneic bone marrow transplantation
Other: laboratory biomarker analysis
Procedure: peripheral blood stem cell transplantation
Procedure: allogeneic hematopoietic stem cell transplantation
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: Calculated for all patients from the date of autologous transplant until the time of death, assessed up to 1 year ] [ Designated as safety issue: No ]
    An observed 1-year PFS of >= 50% would be considered efficacious and worthy of further study.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    Summarized using cumulative incidence estimates. Confidence intervals will be also be estimated.

  • Early non-relapse mortality (NRM) [ Time Frame: At 200 days ] [ Designated as safety issue: No ]
    Recorded and reported on clinical reporting forms (CRFs). 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.

  • Incidence/severity of acute and chronic GVHD [ Time Frame: Up to 84 days ] [ Designated as safety issue: No ]
    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.

  • Immune reconstitution after allografting [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Reconstitution of lymphocyte subsets in peripheral blood [ Time Frame: Up to 84 days ] [ Designated as safety issue: No ]
    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.

  • Overall survival [ Time Frame: At 1 year ] [ Designated as safety issue: No ]
    Estimated by the method of Kaplan and Meier. Confidence intervals will be also be estimated.

  • Incidence of engraftment failure or rejection [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Incidence of infections [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 30
Study Start Date: March 2010
Estimated Primary Completion Date: January 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (autologous HCT/nonmyeloablative donor HCT)
See Detailed Description
Drug: carmustine
Given IV
Other Names:
  • BCNU
  • BiCNU
  • bis-chloronitrosourea
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: cytarabine
Given IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: fludarabine phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: tacrolimus
Given IV or PO
Other Names:
  • FK 506
  • Prograf
Drug: mycophenolate mofetil
Given PO
Other Names:
  • Cellcept
  • MMF
Radiation: total-body irradiation
Undergo TBI
Other Name: TBI
Drug: melphalan
Given IV
Other Names:
  • Alkeran
  • CB-3025
  • L-PAM
  • L-phenylalanine mustard
  • L-Sarcolysin
Procedure: autologous-allogeneic tandem hematopoietic stem cell transplantation
Undergo autologous-donor tandem HCT
Procedure: autologous hematopoietic stem cell transplantation
Undergo autologous PBSC transplant
Procedure: allogeneic bone marrow transplantation
Undergo donor HCT
Other Names:
  • bone marrow therapy, allogeneic
  • bone marrow therapy, allogenic
  • transplantation, allogeneic bone marrow
  • transplantation, allogenic bone marrow
Other: laboratory biomarker analysis
Correlative study
Procedure: peripheral blood stem cell transplantation
Undergo donor HCT
Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell
Procedure: allogeneic hematopoietic stem cell transplantation
Undergo donor HCT

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must have the capacity to give informed consent
  • Detectable tumor prior to mobilization regimen
  • Patients for whom human leukocyte antigens (HLA)-matched unrelated donor search could not be initiated or completed due to insurance reasons, concerns of rapidly progressive disease, and/or discretion of attending physician are eligible for this protocol
  • Patients with stored autologous stem cells will be allowed
  • Stem cells from an identical donor could be used for autologous hematopoietic cell transplant (HCT)
  • Marrow is the preferred source of stem cells from the HLA-haploidentical donor, however, peripheral blood mononuclear cells (PBMC) could be used as stem cell source, after clearance with the Fred Hutchinson Cancer Research Center (FHCRC) principal investigator (PI), in the case of difficulties or contraindications to bone marrow harvest from the donor
  • Cross-over to other tandem autologous-allogeneic research protocol (#1409) will be allowed if a suitable HLA-matched related or unrelated donor is identified before receiving the allogeneic transplantation and if the patient meets the eligibility criteria of the subsequent study
  • Cross-over from other tandem autologous-allogeneic research protocol (#1409) will be allowed if the patient loses the suitable HLA-matched related or unrelated donor but has an available HLA-haploidentical donor before receiving the allogeneic transplantation and if the patient meets the eligibility criteria of the subsequent study
  • Lymphoma: Patients with

    • Diagnosis of non-Hodgkin lymphoma (NHL) or Hodgkin's lymphoma (HL), of any histological grade
    • Refractory or relapsed disease after standard chemotherapy
    • High risk of early relapse following autograft alone
  • Waldenstrom's Macroglobulinemia: must have failed 2 courses of therapy
  • CLL:

    • Patients with either a:

      • Diagnosis of T-cell CLL or T-cell prolymphocytic leukemia (PLL) who have failed initial chemotherapy, patients with T cell CLL or PLL or
      • Diagnosis of B-cell CLL, B-cell small lymphocytic lymphoma, or B-cell CLL that progressed to PLL who either:

        1. Failed to meet National Cancer Institute (NCI) Working Group criteria for complete or partial response after therapy with a regimen containing fludarabine (or another nucleoside analog, e.g. 2-chlorodeoxyadenosine [CDA], pentostatin) or experience disease relapse within 12 months after completing therapy with a regimen containing fludarabine (or another nucleoside analog)
        2. Failed any aggressive chemotherapy regimen, such as fludarabine, cyclophosphamide and rituximab (FCR), at any time point
        3. Have "17p deletion" cytogenetic abnormality and relapsed at any time point after initial chemotherapy
    • Harvesting criteria for autologous HCT:

      • Previously collected PBMC may be used
      • Circulating CLL cells < 5000
    • Marrow involvement with CLL cells < 50%
  • Multiple myeloma (MM): Patients who

    • Have received induction therapy for a minimum of 4 cycles
    • In addition, patients must meet at least one of the following criteria I-IX (I-VII at time of diagnosis or pre-autograft):

      • Any abnormal karyotype by metaphase analysis except for isolated t(11,14),
      • Fluorescent in situ hybridization (FISH) translocation 4:14,
      • FISH translocation 14:16,
      • FISH deletion 17p,
      • Beta2-microglobulin > 5.5 mg/ml,
      • Cytogenetic hypodiploidy
      • Plasmablastic morphology (>= 2%),
      • Recurrent or non-responsive (less than partial remission [PR]) MM after at least two different lines of conventional chemotherapy,
      • Progressive MM after a previous autograft (provided stored autologous CD34 cells are available)
  • Plasma cell leukemia: after induction chemotherapy
  • DONOR: Related donors who are genotypically identical for one HLA haplotype and who may be mismatched at the HLA-A, -B, -C or DRB1 loci of the unshared haplotype with the exception of single HLA-A, -B or -C allele mismatches
  • DONOR: Marrow is the preferred source of stem cells from the HLA-haploidentical donor, however PBMC could be used as stem cell source, after clearance with the FHCRC principal investigator, in the case of difficulties or contraindications to bone marrow harvest from the donor
  • DONOR: In the case that PBMC will be used as stem cell source, ability of donors < 18 years of age to undergo apheresis without use of a vascular access device; vein check must be performed and verified by an apheresis nurse prior to arrival at the Seattle Cancer Care Alliance (SCCA)
  • DONOR: Age >= 12 years of age

Exclusion Criteria:

  • Life expectancy severely limited by disease other than malignancy
  • Seropositive for the human immunodeficiency virus (HIV)
  • Female patients who are pregnant or breastfeeding
  • Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
  • Patients with available HLA matched related donors
  • Central nervous system (CNS) involvement with disease refractory to intrathecal chemotherapy
  • Patients with active non-hematological malignancies (except non-melanoma skin cancers) or those with non-hematological malignancies (except non-melanoma skin cancers) who have been rendered with no evidence of disease, but have a greater than 20% chance of having disease recurrence within 5 years
  • This exclusion does not apply to patients with non-hematologic malignancies that do not require therapy
  • Patients with fungal infection and radiological progression after receipt of amphotericin B or active triazole for greater than 1 month
  • Symptomatic coronary artery disease or ejection fraction < 40% or other cardiac failure requiring therapy (or, if unable to obtain ejection fraction, shortening fraction of < 26%); ejection fraction is required if the patient has a history of anthracyclines or history of cardiac disease; patients with a shortening fraction < 26% may be enrolled if approved by a cardiologist
  • Corrected diffusion capacity of carbon monoxide (DLCO) < 50% of predicted, forced expiratory volume in one second (FEV1) < 50% of predicted, and/or receiving supplementary continuous oxygen; the FHCRC PI of the study must approve of enrollment of all patients with pulmonary nodules
  • Patient with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, bridging fibrosis, and the degree of portal hypertension; the patient will be excluded if he/she is found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy; the patient will be excluded if he/she is found to have uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3mg/dL, and symptomatic biliary disease
  • Karnofsky score < 50% for adult patients
  • Lansky Play-Performance score < 40 for pediatric patients
  • Patient with poorly controlled hypertension despite multiple antihypertensives
  • DONOR: Donor-recipient pairs in which the HLA-mismatch is only in the host-versus-graft (HVG) direction
  • DONOR: Infection with HIV
  • DONOR: Weight < 20 kg
  • DONOR: A positive anti-donor cytotoxic crossmatch
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01008462

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Mohamed L. Sorror    206-667-2765      
Principal Investigator: Mohamed L. Sorror         
United States, Wisconsin
Froedtert and the Medical College of Wisconsin Completed
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: Mohamed Sorror Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT01008462     History of Changes
Other Study ID Numbers: 2241.00, NCI-2009-01334, 2241.00, P30CA015704, P01CA078902
Study First Received: November 4, 2009
Last Updated: June 10, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma
Leukemia
Hodgkin Disease
Lymphoma, Mantle-Cell
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Large B-Cell, Diffuse
Lymphoma, T-Cell
Burkitt Lymphoma
Lymphoma, Large-Cell, Immunoblastic
Mycosis Fungoides
Sezary Syndrome
Lymphoma, T-Cell, Cutaneous
Waldenstrom Macroglobulinemia
Lymphoma, Large-Cell, Anaplastic
Lymphoma, B-Cell
Lymphomatoid Granulomatosis
Immunoblastic Lymphadenopathy
Lymphoma, Extranodal NK-T-Cell
Lymphoma, T-Cell, Peripheral
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on September 18, 2014