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 Description

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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

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Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	30 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
Estimated Primary Completion Date :	January 31, 2020

Arms and Interventions

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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

Outcome Measures

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Primary Outcome Measures :

1. Progression-free survival (PFS) [ Time Frame: From the date of autologous transplant until the time of death, assessed up to 1 year ]
   An observed 1-year PFS of >= 50% would be considered efficacious and worthy of further study.

Secondary Outcome Measures :

1. 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.
2. Early non-relapse mortality (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.
3. Immune reconstitution after allografting [ Time Frame: Up to 1 year ]
4. Incidence of acute and chronic graft versus host disease (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.
5. Incidence of engraftment failure or rejection [ Time Frame: Up to 1 year ]
6. Incidence of infections [ Time Frame: Up to 1 year ]
7. Overall survival [ Time Frame: At 1 year ]
   Estimated by the method of Kaplan and Meier. Confidence intervals will also be estimated.
8. 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.
9. 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.
10. Severity of acute and chronic graft versus host disease (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.

Eligibility Criteria

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Ages Eligible for Study:	up to 75 Years (Child, Adult, Senior)
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

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, Washington
Fred Hutch/University of Washington Cancer Consortium	Recruiting
Seattle, Washington, United States, 98109
Contact: Mohamed L. Sorror 206-667-6298 msorror@fhcrc.org
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

National Cancer Institute (NCI)

Investigators

Principal Investigator:	Mohamed Sorror	Fred Hutch/University of Washington Cancer Consortium

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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
Last Update Posted:	December 28, 2017
Last Verified:	December 2017

Additional relevant 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, B-Cell; Leukemia, Prolymphocytic, T-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; Cyclophosphamide; Tacrolimus