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
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
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 Genetic: fluorescence in situ hybridization Other: flow cytometry Genetic: RNA analysis Other: laboratory biomarker analysis Genetic: cytogenetic analysis Genetic: polymerase chain reaction 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 |
- 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.
- 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 GVHD [ Time Frame: At 120 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:
Drug: etoposide
Given IV
Other Names:
Drug: cytarabine
Given IV
Other Names:
Drug: fludarabine phosphate
Given IV
Other Names:
Drug: cyclophosphamide
Given IV
Other Names:
Drug: tacrolimus
Given IV or PO
Other Names:
Drug: mycophenolate mofetil
Given PO
Other Names:
Radiation: total-body irradiation
Undergo TBI
Other Name: TBI
Drug: melphalan
Given IV
Other Names:
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:
Genetic: fluorescence in situ hybridization
Correlative study
Other Name: fluorescence in situ hybridization (FISH)
Other: flow cytometry
Correlative study
Genetic: RNA analysis
Correlative study
Other: laboratory biomarker analysis
Correlative study
Genetic: cytogenetic analysis
Correlative study
Genetic: polymerase chain reaction
Correlative study
Other Name: PCR
Procedure: peripheral blood stem cell transplantation
Undergo donor HCT
Other Names:
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 |
Inclusion Criteria:
- Must have the capacity to give informed consent
- Detectable tumor on radiographic studies or bone marrow biopsy 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:
- 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)
- Failed any aggressive chemotherapy regimen, such as fludarabine, cyclophosphamide and rituximab (FCR), at any time point
- 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; 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| United States, Washington | |
| Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Recruiting |
| Seattle, Washington, United States, 98109 | |
| Contact: Seattle Cancer Care Alliance 800-804-8824 | |
| Principal Investigator: Mohamed L. Sorror | |
| United States, Wisconsin | |
| Froedtert and the Medical College of Wisconsin | Recruiting |
| Milwaukee, Wisconsin, United States, 53226 | |
| Contact: Jeanne Palmer 414-805-6800 | |
| Principal Investigator: Jeanne Palmer | |
| Principal Investigator: | Mohamed Sorror | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium |
More Information
No publications provided
| ClinicalTrials.gov Identifier: | NCT01008462 History of Changes |
| Other Study ID Numbers: | 2241.00, NCI-2009-01334, P01CA078902 |
| Study First Received: | November 4, 2009 |
| Last Updated: | December 21, 2012 |
| Health Authority: | United States: Institutional Review Board |
Additional relevant MeSH terms:
|
Burkitt Lymphoma Hodgkin Disease Immunoblastic Lymphadenopathy Leukemia Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Lymphoma Lymphoma, Follicular Lymphoma, Non-Hodgkin Lymphomatoid Granulomatosis Waldenstrom Macroglobulinemia Multiple Myeloma Neoplasms, Plasma Cell Mycoses Mycosis Fungoides |
Sezary Syndrome Lymphoma, B-Cell Lymphoma, Large B-Cell, Diffuse Lymphoma, Large-Cell, Immunoblastic Precursor Cell Lymphoblastic Leukemia-Lymphoma Lymphoma, T-Cell Lymphoma, T-Cell, Cutaneous Lymphoma, T-Cell, Peripheral Lymphoma, Large-Cell, Anaplastic Lymphoma, B-Cell, Marginal Zone Lymphoma, Extranodal NK-T-Cell Lymphoma, Mantle-Cell Epstein-Barr Virus Infections Herpesviridae Infections DNA Virus Infections |
ClinicalTrials.gov processed this record on May 16, 2013