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

NCT01008462 | Completed Phase 2 Results DMC

• 3 other identifiers: 2241.00NCI-2009-01334P30CA015704
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Event-Free Survival (EFS)

  Number of patients surviving without relapsed/progressive disease

  1 Year post-autograft

Secondary Outcomes (6)

• Number of Patients With Relapsed/Progressive Disease

  1 year post-autograft

• Overall Survival

  1 year post-autograft

• Number of Patients With Grade II-IV Acute Graft-versus-Host-Disease and/or Chronic Extensive Graft-versus-Host-Disease

  1 year post-allograft,

• Non-relapse Mortality (NRM)

  200 days and 1 Year post-allograft

• Number of Patients Who Engrafted

  Day 84 post-allograft

Study Arms (1)

Treatment (autologous HCT, donor HCT)

EXPERIMENTAL

See Detailed Description

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

Interventions

Allogeneic Bone Marrow Transplantation PROCEDURE

Undergo donor HCT

Also known as: Allo BMT, Allogeneic BMT

Treatment (autologous HCT, donor HCT)

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo donor HCT

Also known as: Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT

Treatment (autologous HCT, donor HCT)

Autologous Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo autologous PBSC transplant

Also known as: Autologous Hematopoietic Cell Transplantation, autologous stem cell transplantation

Treatment (autologous HCT, donor HCT)

Autologous-Allogeneic Tandem Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo autologous-donor tandem HCT

Also known as: auto-allo HCT

Treatment (autologous HCT, donor HCT)

Carmustine DRUG

Given IV

Also known as: 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

Treatment (autologous HCT, donor HCT)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-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

Treatment (autologous HCT, donor HCT)

Cytarabine DRUG

Given IV

Also known as: .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

Treatment (autologous HCT, donor HCT)

Etoposide DRUG

Given IV

Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16-213, VP-16, VP-16-213

Treatment (autologous HCT, donor HCT)

Fludarabine Phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586

Treatment (autologous HCT, donor HCT)

Laboratory Biomarker Analysis OTHER

Correlative study

Treatment (autologous HCT, donor HCT)

Melphalan DRUG

Given IV

Also known as: 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

Treatment (autologous HCT, donor HCT)

Mycophenolate Mofetil DRUG

Given PO

Also known as: Cellcept, MMF

Treatment (autologous HCT, donor HCT)

Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo donor HCT

Also known as: PBPC transplantation, PBSCT, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplant, Peripheral Stem Cell Transplantation

Treatment (autologous HCT, donor HCT)

Tacrolimus DRUG

Given IV or PO

Also known as: FK 506, Fujimycin, Hecoria, Prograf, Protopic

Treatment (autologous HCT, donor HCT)

Total-Body Irradiation RADIATION

Undergo TBI

Also known as: Total Body Irradiation, Whole-Body Irradiation

Treatment (autologous HCT, donor HCT)

Eligibility Criteria

• Age: Up to 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Froedtert and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Leukemia, Prolymphocytic, B-Cell; Chromosome 17 deletion; Leukemia, Plasma Cell; Hodgkin Disease; Lymphoma, Non-Hodgkin; Leukemia, Lymphocytic, Chronic, B-Cell; Multiple Myeloma; Leukemia, Prolymphocytic, T-Cell; Waldenstrom Macroglobulinemia

Interventions

Carmustine; carmustine, poliferprosan 20 drug combination; Cyclophosphamide; Cytarabine; Etoposide; fludarabine phosphate; Melphalan; Mycophenolic Acid; Peripheral Blood Stem Cell Transplantation; Tacrolimus; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Leukemia, Prolymphocytic; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Lymphoma; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Leukemia, T-Cell

Intervention Hierarchy (Ancestors)

Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Macrolides; Lactones; Radiotherapy; Investigative Techniques

Results Point of Contact

• Title: Dr. Mohamed L. Sorror
• Organization: Fred Hutchinson Cancer Research Center

msorror@fredhutch.org

(206) 667-6298

Study Officials

• Mohamed Sorror

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2009
• First Posted: November 5, 2009
• Study Start: March 18, 2010
• Primary Completion: June 30, 2018
• Study Completion: June 30, 2018
• Last Updated: June 11, 2019
• Results First Posted: May 29, 2019

Record last verified: 2019-05

Locations

US (2)