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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

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ClinicalTrials.gov Identifier: NCT01008462
Recruitment Status : Completed
First Posted : November 5, 2009
Results First Posted : May 29, 2019
Last Update Posted : June 11, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center

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.

Condition or disease Intervention/treatment Phase
B-Cell Prolymphocytic Leukemia Hypodiploidy Loss of Chromosome 17p Plasma Cell Leukemia Progression of Multiple Myeloma or Plasma Cell Leukemia Recurrent Adult Hodgkin Lymphoma Recurrent Adult Non-Hodgkin Lymphoma Recurrent Childhood Hodgkin Lymphoma Recurrent Childhood Non-Hodgkin Lymphoma Recurrent Chronic Lymphocytic Leukemia Recurrent Plasma Cell Myeloma Recurrent Small Lymphocytic Lymphoma Refractory Childhood Hodgkin Lymphoma Refractory Chronic Lymphocytic Leukemia Refractory Non-Hodgkin Lymphoma Refractory Plasma Cell Myeloma Refractory Small Lymphocytic Lymphoma t(14;16) t(4;14) T-Cell Prolymphocytic Leukemia Waldenstrom Macroglobulinemia Procedure: Allogeneic Bone Marrow Transplantation Procedure: Allogeneic Hematopoietic Stem Cell Transplantation Procedure: Autologous Hematopoietic Stem Cell Transplantation Procedure: Autologous-Allogeneic Tandem Hematopoietic Stem Cell Transplantation Drug: Carmustine Drug: Cyclophosphamide Drug: Cytarabine Drug: Etoposide Drug: Fludarabine Phosphate Other: Laboratory Biomarker Analysis Drug: Melphalan Drug: Mycophenolate Mofetil Procedure: Peripheral Blood Stem Cell Transplantation Drug: Tacrolimus Radiation: Total-Body Irradiation Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Intervention Model: Single Group Assignment
Masking: None (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
Actual Study Start Date : March 18, 2010
Actual Primary Completion Date : June 30, 2018
Actual Study Completion Date : June 30, 2018


Arm Intervention/treatment
Experimental: Treatment (autologous HCT, donor HCT)
See Detailed Description
Procedure: Allogeneic Bone Marrow Transplantation
Undergo donor HCT
Other Names:
  • Allo BMT
  • Allogeneic BMT

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Undergo donor HCT
Other Names:
  • Allogeneic Hematopoietic Cell Transplantation
  • Allogeneic Stem Cell Transplantation
  • HSC
  • HSCT

Procedure: Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous PBSC transplant
Other Names:
  • Autologous Hematopoietic Cell Transplantation
  • autologous stem cell transplantation

Procedure: Autologous-Allogeneic Tandem Hematopoietic Stem Cell Transplantation
Undergo autologous-donor tandem HCT
Other Name: auto-allo HCT

Drug: Carmustine
Given IV
Other Names:
  • BCNU
  • Becenum
  • Becenun
  • BiCNU
  • Bis(chloroethyl) Nitrosourea
  • Bis-Chloronitrosourea
  • Carmubris
  • Carmustin
  • Carmustinum
  • FDA 0345
  • Gliadel
  • N,N'-Bis(2-chloroethyl)-N-nitrosourea
  • Nitrourean
  • Nitrumon
  • SK 27702
  • SRI 1720
  • WR-139021

Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719

Drug: Cytarabine
Given IV
Other Names:
  • .beta.-Cytosine arabinoside
  • 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone
  • 1-.beta.-D-Arabinofuranosylcytosine
  • 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone
  • 1-Beta-D-arabinofuranosylcytosine
  • 1.beta.-D-Arabinofuranosylcytosine
  • 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-
  • 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-
  • Alexan
  • Ara-C
  • ARA-cell
  • Arabine
  • Arabinofuranosylcytosine
  • Arabinosylcytosine
  • Aracytidine
  • Aracytin
  • Aracytine
  • Beta-cytosine Arabinoside
  • CHX-3311
  • Cytarabinum
  • Cytarbel
  • Cytosar
  • Cytosine Arabinoside
  • Cytosine-.beta.-arabinoside
  • Cytosine-beta-arabinoside
  • Erpalfa
  • Starasid
  • Tarabine PFS
  • U 19920
  • U-19920
  • Udicil
  • WR-28453

Drug: Etoposide
Given IV
Other Names:
  • Demethyl Epipodophyllotoxin Ethylidine Glucoside
  • EPEG
  • Lastet
  • Toposar
  • Vepesid
  • VP 16-213
  • VP-16
  • VP-16-213

Drug: Fludarabine Phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
  • Beneflur
  • Fludara
  • SH T 586

Other: Laboratory Biomarker Analysis
Correlative study

Drug: Melphalan
Given IV
Other Names:
  • Alanine Nitrogen Mustard
  • CB-3025
  • L-PAM
  • L-Phenylalanine Mustard
  • L-sarcolysin
  • L-Sarcolysin Phenylalanine mustard
  • L-Sarcolysine
  • Melphalanum
  • Phenylalanine Mustard
  • Phenylalanine nitrogen mustard
  • Sarcoclorin
  • Sarkolysin
  • WR-19813

Drug: Mycophenolate Mofetil
Given PO
Other Names:
  • Cellcept
  • MMF

Procedure: Peripheral Blood Stem Cell Transplantation
Undergo donor HCT
Other Names:
  • PBPC transplantation
  • PBSCT
  • Peripheral Blood Progenitor Cell Transplantation
  • Peripheral Stem Cell Support
  • Peripheral Stem Cell Transplant
  • Peripheral Stem Cell Transplantation

Drug: Tacrolimus
Given IV or PO
Other Names:
  • FK 506
  • Fujimycin
  • Hecoria
  • Prograf
  • Protopic

Radiation: Total-Body Irradiation
Undergo TBI
Other Names:
  • Total Body Irradiation
  • Whole-Body Irradiation




Primary Outcome Measures :
  1. Event-Free Survival (EFS) [ Time Frame: 1 Year post-autograft ]
    Number of patients surviving without relapsed/progressive disease


Secondary Outcome Measures :
  1. Number of Patients With Relapsed/Progressive Disease [ Time Frame: 1 year post-autograft ]

    Relapse/Progression defined as:

    Nodes, liver, and/or spleen ≥50% increased or new by physical exam / imaging studies.

    Circulating lymphocytes ≥50% increased by morphology and/or flow cytometry. Richter's transformation by lymph node biopsy .


  2. Overall Survival [ Time Frame: 1 year post-autograft ]
    Number of patients surviving one year post-autograft

  3. Number of Patients With Grade II-IV Acute Graft-versus-Host-Disease and/or Chronic Extensive Graft-versus-Host-Disease [ Time Frame: 1 year post-allograft, ]

    aGVHD The diagnosis of aGVHD is identified through various stages and grading of the disease related to Skin (Rash), Gut (Diarrhea, Nausea/vomiting and/or anorexia) and the liver (Bilirubin) assessed by severity and grading scale outlined in the section Grafts vs Hosts by Sullivan (1999).

    GVHD Grades Grade I: 1-2 Skin Rash; No gut or liver involvement Grade II: Stage 1-3 Skin rash; Stage 1 gut and/or stage 1 liver involvement Grade III: Stage 2-4 gut involvement and/or stage 2-4 liver involvement with or without rash Grade IV: Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death

    CGVHD The diagnosis of cGVHD requires at least one manifestation that is distinctive for chronic GVHD as opposed to acute GVHD. In all cases, infection and others causes must be ruled out in the differential diagnosis of chronic GVHD.


  4. Non-relapse Mortality (NRM) [ Time Frame: 200 days and 1 Year post-allograft ]
    Number of patients with non-relapse mortalities.

  5. Number of Patients Who Engrafted [ Time Frame: Day 84 post-allograft ]
    Number of patients with donor engraftment.

  6. Number of Patients Who Had Infections [ Time Frame: 1 Year post-autograft ]
    Number of patients who had infections.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   up to 75 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must have the capacity to give informed consent
  • Detectable tumor prior to mobilization regimen
  • 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, in the case of difficulties or contraindications to bone marrow harvest from the donor
  • Cross-over to other tandem autologous-allogeneic research protocol (#1409 or other appropriate protocol) 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 or other appropriate protocol) 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 (B2)-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 cluster of differentiation [CD]34 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
  • Female patients who are pregnant or breastfeeding
  • Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
  • 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 the lungs for carbon monoxide (DLCO) < 50% of predicted, forced expiratory volume in one second (FEV1) < 50% of predicted, and/or receiving supplementary continuous oxygen; the FHCRC principal investigator (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, 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 > 3 mg/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 human immunodeficiency virus (HIV)
  • DONOR: Weight < 20 kg
  • DONOR: A positive anti-donor cytotoxic crossmatch

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01008462


Locations
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United States, Washington
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
United States, Wisconsin
Froedtert and the Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Mohamed Sorror Fred Hutch/University of Washington Cancer Consortium
  Study Documents (Full-Text)

Documents provided by Fred Hutchinson Cancer Research Center:

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Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT01008462     History of Changes
Other Study ID Numbers: 2241.00
NCI-2009-01334 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2241.00 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
P30CA015704 ( U.S. NIH Grant/Contract )
First Posted: November 5, 2009    Key Record Dates
Results First Posted: May 29, 2019
Last Update Posted: June 11, 2019
Last Verified: May 2019
Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Leukemia
Multiple Myeloma
Neoplasms, Plasma Cell
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Hodgkin Disease
Waldenstrom Macroglobulinemia
Leukemia, Prolymphocytic
Leukemia, Plasma Cell
Leukemia, Prolymphocytic, T-Cell
Leukemia, Prolymphocytic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Leukemia, B-Cell
Leukemia, T-Cell
Cytarabine
Mycophenolic Acid