Donor Stem Cell Transplant in Treating Patients With High-Risk Hematologic Cancer

• Sponsor: Northside Hospital, Inc. (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00818961
• Collaborator: Blood and Marrow Transplant Group of Georgia (Other)
• Enrollment: 36
• Location: 1
• Arm: 1
• Duration (Months): 82
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

RATIONALE: Giving low doses of chemotherapy before a donor stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving a monoclonal antibody, such as alemtuzumab, before transplant and tacrolimus and methotrexate after transplant may stop this from happening.

PURPOSE: This phase II trial is studying the side effects of donor stem cell transplant and to see how well it works in treating patients with high-risk hematologic cancer.

Condition or Disease	Intervention/Treatment	Phase
Leukemia; Lymphoma; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases	Biological: alemtuzumab; Biological: graft-versus-tumor induction therapy; Biological: rituximab; Drug: busulfan; Drug: cyclophosphamide; Drug: fludarabine phosphate; Drug: methotrexate; Drug: tacrolimus; Procedure: allogeneic bone marrow transplantation	Phase 2

Detailed Description

OBJECTIVES:

• To evaluate the safety and toxicity of a reduced-intensity conditioning regimen followed by allogeneic bone marrow or peripheral blood stem cell transplantation from an HLA-matched unrelated donor in patients with high-risk hematologic malignancies.

• To evaluate engraftment by peripheral blood chimerism analysis.

• To determine the incidence and severity of acute and chronic graft-versus-host disease following the transplant.

• To examine the possibility of controlling hematologic malignancies by induction of a graft-versus-leukemia/tumor effect.

• To determine the disease-free survival, relapse, transplant-related mortality, and death from all causes.

OUTLINE:

• Reduced-intensity conditioning regimen: Patients receive 1 of 2 conditioning regimens according to diagnosis.

• Regimen 1 (acute leukemia, myelodysplastic syndromes, myeloproliferative syndrome, or chronic myelogenous leukemia): Patients receive fludarabine phosphate IV over 30 minutes and busulfan IV over 3 hours on days -6 to -3 or orally 4 times daily on days -7 to -3.

• Regimen 2 (lymphoproliferative malignancies): Patients receive fludarabine phosphate IV over 30 minutes and cyclophosphamide IV over 1 hour on days -5 to -3. Patients with CD20+ malignancies also receive rituximab IV over 4-6 hours on days -13, -6, 1, and 8.

• Transplantation: Patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on day 0.

• Graft-versus-host disease (GVHD) prophylaxis: Patients receive low-dose alemtuzumab subcutaneously on days -11 to -9 and tacrolimus IV over 24 hours beginning on day -3 and then orally twice daily beginning on day 14 and continuing until day 60, followed by a taper until day 180 in the absence of clinically significant GVHD. Patients also receive methotrexate on days 1, 3, and 6.

Patients who exhibit persistent mixed chimerism or disease relapse/progression despite full withdrawal of immunosuppression may receive up to 3 donor lymphocyte infusions.

Blood samples are taken on days 30, 60, and 100 and then every 4 weeks thereafter for chimerism studies by PCR analysis.

After completion of study therapy, patients are followed periodically for up to 60 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Reduced Intensity Allogeneic Stem Cell Transplantation With Matched Unrelated Donors for Patients With Hematologic Malignancies
• Study Start Date: May 1, 2005
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: Mar 1, 2012

Arms and Interventions

Arm

Intervention/Treatment

Other: Hematopoietic Stem Cell Transplantation All patients receive a hematopoietic stem cell transplant using one of two chemotherapy regimens based on donor type

Biological: alemtuzumab; 43 mg subcutaneously over 3 days (3 mg on day -11, 10 mg on day -10, 30 mg on day -9); Other Names: Campath ; Biological: graft-versus-tumor induction therapy; curative potential of allogeneic transplant results from the immune anti-tumor effect of donor cells or GVT/GVL; Biological: rituximab; in patients with Cd20+ malignancies: rituximab 375 mg/m*2 day -13. rituximab 1000 mg/m*2 on days, -6, +1, +8.; Other Names: Rituxan ; Drug: busulfan; For patients with AML, CML, MDS, MPS and ALL only: IV or oral busulfan may be given IV busulfan: 130 mg/m2 over 3 hours once daily on days -6, -5, -4 and -3 Oral busulfan: taken every 6 hours x 15 doses beginning on day -7 at 6pm and continuing through day -3 at 6am. 1 mg/kg test dose will be given prior to day -7 and PK samples will be drawn to calculate AUC.; Drug: cyclophosphamide; 750 mg/m2 infused over 1 hour once daily on days -5, -4 and -3. Cyclophosphamide will be started approximately 4 hours after the start of Fludarabine; Other Names: Cytoxan ; Drug: fludarabine phosphate; For patients with CLL, NHL & HD: 30 mg/m2 infused over 30 minutes once daily on days -5, -4 and -3 For patients with AML, CML, MDS, MPS and ALL: 40 mg/m2 infused over 30 minutes once daily on days -6, -5, -4 and -3.; Other Names: Fludara ; Drug: methotrexate; 5 mg/m2 administered on days +1, +3 and +6; Drug: tacrolimus; 0.03mg/kg/day infused over 24 hours starting on day -1 and switched to oral (twice daily divided dose) on day 14 or when able to tolerate PO; Other Names: Prograf; FK506 ; Procedure: allogeneic bone marrow transplantation; Recipients will receive an allogeneic transplant on day 0 after receiving high-dose chemotherapy. This trial uses matched unrelated donor stem cells.; Other Names: HSCT, allo transplant

Outcome Measures

Primary Outcome Measures

1. Survival at Day 100 [100 day]

   Survival at Day 100

Secondary Outcome Measures

1. Overall Survival at 1 Year [1 year]

   Evaluation of overall survival at 1 year (# of patients who are alive at 1 year post-transplant)

2. Non-relapse Mortality at Day 100 [Day 100]

   patients are evaluable for their cause of death at Day 100

3. Non-relapse Mortality at 1 Year Post-transplant [1 year]

   Number of patients who died of non-relapse causes at one year. this is in clusive of all patients who were transplanted on study even though only 10 patients died at by 1 year time point. This outcome will be referenced in the donor chimerism outcome. Only 26/36 patients were eligible for this time point as that is all that were alive.

4. Complete Donor Chimerism [2 years]

   Complete donor chimerism (defined as >/= 95% donor cells in peripheral blood CD3+ and CD33+ was measured.

5. Neutrophil Recovery [Day 100]

   The number of patients experiencing neutrophil recovery post transplant

6. Platelet Engraftment [Day 100]

   The number of patients experiencing platelet engraftment post-transplant

7. Number of Patients Requiring the Use of Donor Leukocyte Infusion (DLI) for Early Mixed T-cell Chimerism [Day 100]

   DLI is used for patients with mixed chimerism following transplant

8. Number of Patients Experiencing Grade 2-4 Acute Graft-versus-host Disease Post-transplant [patients were followed for 2 years]

   patients experiencing acute graft versus host disease post-transplant

9. Number of Patients Experiencing Chronic Graft Versus Host Disease [>100 days post-transplant]

10. Number of Patients Experiencing Veno-occlusive Disease (VOD) Post-transplant [4 years]

    Patients will be evaluated up to 4 years post transplant

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 72 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

• Diagnosis of one of the following hematological malignancies:

• CML, with 1 of the following:

• In first CP AND failed imatinib mesylate therapy, defined as failure to obtain a hematologic remission at 3 months or a major cytogenetic response (i.e., Ph+ cells < 35%) at 6 months or demonstrated clonal evolution or disease progression during therapy

• In accelerated phase with < 15% blasts

• In blast crisis that has entered into a second CP following induction chemotherapy

• AML, with 1 of the following:

• In second or subsequent complete remission (CR) (i.e., < 5% blasts by morphology, no residual leukemia by flow cytometry, and absence of cytogenetic abnormalities)

• Failed primary induction chemotherapy, but subsequently entered into a CR with ≤ 2 subsequent re-induction chemotherapy treatment(s)

• In first CR with intermediate-risk or poor-risk cytogenetics

• ALL with 1 of the following:

• In second or subsequent CR

• In first CR AND presence of t(9;22)

• MDS, with the following:

• High-risk disease, defined by IPSS score of ≥ 1.5 at diagnosis AND meets 1 of the following criteria:

• ≤ 10% blasts at diagnosis

• In morphologic CR (< 5% blasts) following cytoreductive chemotherapy

• CMML, with 1 of the following:

• ≤ 10% blasts at diagnosis

• In morphologic CR (< 5% blasts) following cytoreductive chemotherapy

• CLL/PLL with the following:

• Rai stage I-IV disease

• Failed ≥ 1 prior chemotherapy regimen (including fludarabine phosphate) or ASCT

• Documented chemosensitive or stable, non-bulky disease prior to transplant, defined as < 20% bone marrow involvement AND lymph node size < 3 cm in axial diameter

• No bulky tumor masses, elevated lactate dehydrogenase (LDH), B symptoms, or progressive disease prior to transplant

• Low-grade non-Hodgkin lymphoma (NHL) (i.e., small lymphocytic lymphoma, follicular center lymphoma [grade 1 or 2], marginal zone lymphoma, or B-cell lymphoma), with the following criteria:

• Failed ≥ 1 prior chemotherapy regimen or ASCT

• Documented chemosensitive or stable, non-bulky disease prior to transplant, defined as < 20% bone marrow involvement AND lymph node size < 3 cm in axial diameter

• Received ≤ 3 prior chemotherapy regimens (monoclonal antibody therapy and involved-field radiotherapy are not considered a prior regimen)

• No bulky tumor masses, elevated LDH, B symptoms, or progressive disease prior to transplant

• Mantle cell lymphoma, with the following:

• Failed to achieve remission or recurred after either conventional chemotherapy or ASCT

• Responsive or stable disease to most recent prior therapy

• No bulky tumor masses, elevated LDH, B symptoms, or progressive disease prior to transplant

• Intermediate-grade NHL (i.e., follicular center lymphoma [grade 3] or diffuse large cell lymphoma), meeting the following criteria:

• Failed to achieve remission or recurred after either conventional chemotherapy or ASCT

• Documented chemosensitive, non-bulky disease prior to transplant, defined as at least a partial remission to salvage chemotherapy (≥ 50% reduction in diameter of all disease sites)

• No bulky tumor masses, elevated LDH, B symptoms, or progressive disease prior to transplant

• Hodgkin lymphoma, with the following:

• Relapsed after prior ASCT OR after ≥ 2 combination chemotherapy regimens and ineligible for ASCT

• Documented chemosensitive, non-bulky disease prior to transplant, defined as at least a partial remission to salvage chemotherapy (≥ 50% reduction in diameter of all disease sites)

• No bulky tumor masses, elevated LDH, B symptoms, or progressive disease prior to transplant

• Peripheral T-cell NHL, with the following:

• Failed to achieve remission or recurred after either conventional chemotherapy or ASCT

• Documented chemosensitive, non-bulky disease prior to transplant, defined as at least a partial remission to salvage chemotherapy (≥ 50% reduction in diameter of all disease sites)

• No bulky tumor masses, elevated LDH, B symptoms, or progressive disease prior to transplant

• Myeloproliferative syndrome with poor risk features, meeting 1 of the following criteria:

• < 55 years old AND Lille score of 1

• Lille score of 2

• HgB < 10 g/dL AND abnormal karyotype

• High-risk disease, with 1 of the following:

• Age 40-72 years

• Any age AND deemed to be at significantly increased risk of morbidity and death following a standard, myeloablative unrelated donor stem cell transplant (e.g., received extensive prior therapy, including ASCT)

• HLA-matched unrelated donor available, with 1 of the following:

• 8/8 match at HLA-A, B, C, or DR loci by high-resolution genotyping

• Single allelic mismatch at either the HLA-B or HLA-C loci donor by high-resolution molecular typing

• No single allelic mismatch at HLA-A or HLA-DR loci

• KPS 80-100%

• Adapted weighted Charlson Comorbidity Index < 3

• Serum creatinine ≤ 2.0 mg/dL

• AST or ALT < 3 times upper limit of normal (ULN)

• Total bilirubin < 1.5 times ULN

• LVEF ≥ 45%

• DLCO > 50%

• No hypoxia at rest with oxygen saturation < 92% on room air (corrected with bronchodilator therapy)

• No other severe pulmonary function abnormalities

• No HIV infection

• No active hepatitis B or C infection that, in the opinion of a gastroenterologist or the transplant committee, places the patient at moderate to high risk for developing severe hepatic disease

• No active opportunistic infection (e.g., fungal pneumonia, tuberculosis, or viral infection)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Blood and Marrow Transplant Group of Georgia	Atlanta	Georgia	United States	30342

Sponsors and Collaborators

• Northside Hospital, Inc.
• Blood and Marrow Transplant Group of Georgia

Investigators

• Principal Investigator: Scott R. Solomon, MD, Blood and Marrow Transplant Group of Georgia

Study Documents (Full-Text)

None provided.

More Information

Publications

• Anderson JE, Anasetti C, Appelbaum FR, Schoch G, Gooley TA, Hansen JA, Buckner CD, Sanders JE, Sullivan KM, Storb R. Unrelated donor marrow transplantation for myelodysplasia (MDS) and MDS-related acute myeloid leukaemia. Br J Haematol. 1996 Apr;93(1):59-67.
• Byrne JL, Stainer C, Cull G, Haynes AP, Bessell EM, Hale G, Waldmann H, Russell NH. The effect of the serotherapy regimen used and the marrow cell dose received on rejection, graft-versus-host disease and outcome following unrelated donor bone marrow transplantation for leukaemia. Bone Marrow Transplant. 2000 Feb;25(4):411-7.
• Champlin RE, Passweg JR, Zhang MJ, Rowlings PA, Pelz CJ, Atkinson KA, Barrett AJ, Cahn JY, Drobyski WR, Gale RP, Goldman JM, Gratwohl A, Gordon-Smith EC, Henslee-Downey PJ, Herzig RH, Klein JP, Marmont AM, O'Reilly RJ, Ringdén O, Slavin S, Sobocinski KA, Speck B, Weiner RS, Horowitz MM. T-cell depletion of bone marrow transplants for leukemia from donors other than HLA-identical siblings: advantage of T-cell antibodies with narrow specificities. Blood. 2000 Jun 15;95(12):3996-4003.
• Davies SM, Kollman C, Anasetti C, Antin JH, Gajewski J, Casper JT, Nademanee A, Noreen H, King R, Confer D, Kernan NA. Engraftment and survival after unrelated-donor bone marrow transplantation: a report from the national marrow donor program. Blood. 2000 Dec 15;96(13):4096-102.
• Diaconescu R, Flowers CR, Storer B, Sorror ML, Maris MB, Maloney DG, Sandmaier BM, Storb R. Morbidity and mortality with nonmyeloablative compared with myeloablative conditioning before hematopoietic cell transplantation from HLA-matched related donors. Blood. 2004 Sep 1;104(5):1550-8. Epub 2004 May 18.
• Escalón MP, Champlin RE, Saliba RM, Acholonu SA, Hosing C, Fayad L, Giralt S, Ueno NT, Maadani F, Pro B, Donato M, McLaughlin P, Khouri IF. Nonmyeloablative allogeneic hematopoietic transplantation: a promising salvage therapy for patients with non-Hodgkin's lymphoma whose disease has failed a prior autologous transplantation. J Clin Oncol. 2004 Jun 15;22(12):2419-23.
• Faulkner RD, Craddock C, Byrne JL, Mahendra P, Haynes AP, Prentice HG, Potter M, Pagliuca A, Ho A, Devereux S, McQuaker G, Mufti G, Yin JL, Russell NH. BEAM-alemtuzumab reduced-intensity allogeneic stem cell transplantation for lymphoproliferative diseases: GVHD, toxicity, and survival in 65 patients. Blood. 2004 Jan 15;103(2):428-34. Epub 2003 Sep 11.
• Giralt S, Estey E, Albitar M, van Besien K, Rondón G, Anderlini P, O'Brien S, Khouri I, Gajewski J, Mehra R, Claxton D, Andersson B, Beran M, Przepiorka D, Koller C, Kornblau S, Kørbling M, Keating M, Kantarjian H, Champlin R. Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. Blood. 1997 Jun 15;89(12):4531-6.
• Hansen JA, Gooley TA, Martin PJ, Appelbaum F, Chauncey TR, Clift RA, Petersdorf EW, Radich J, Sanders JE, Storb RF, Sullivan KM, Anasetti C. Bone marrow transplants from unrelated donors for patients with chronic myeloid leukemia. N Engl J Med. 1998 Apr 2;338(14):962-8.
• Izutsu K, Kanda Y, Ohno H, Sao H, Ogawa H, Miyazaki Y, Kawa K, Kodera Y, Kato S, Morishima Y, Hirai H; Japan Marrow Donor Program. Unrelated bone marrow transplantation for non-Hodgkin lymphoma: a study from the Japan Marrow Donor Program. Blood. 2004 Mar 1;103(5):1955-60. Epub 2003 Nov 6.
• Jones RJ, Ambinder RF, Piantadosi S, Santos GW. Evidence of a graft-versus-lymphoma effect associated with allogeneic bone marrow transplantation. Blood. 1991 Feb 1;77(3):649-53.
• Kernan NA, Bartsch G, Ash RC, Beatty PG, Champlin R, Filipovich A, Gajewski J, Hansen JA, Henslee-Downey J, McCullough J, et al. Analysis of 462 transplantations from unrelated donors facilitated by the National Marrow Donor Program. N Engl J Med. 1993 Mar 4;328(9):593-602.
• Khouri IF, Lee MS, Saliba RM, Andersson B, Anderlini P, Couriel D, Hosing C, Giralt S, Korbling M, McMannis J, Keating MJ, Champlin RE. Nonablative allogeneic stem cell transplantation for chronic lymphocytic leukemia: impact of rituximab on immunomodulation and survival. Exp Hematol. 2004 Jan;32(1):28-35.
• McGlave PB, Shu XO, Wen W, Anasetti C, Nademanee A, Champlin R, Antin JH, Kernan NA, King R, Weisdorf DJ. Unrelated donor marrow transplantation for chronic myelogenous leukemia: 9 years' experience of the national marrow donor program. Blood. 2000 Apr 1;95(7):2219-25.
• Mehta J, Singhal S. Graft-versus-myeloma. Bone Marrow Transplant. 1998 Nov;22(9):835-43. Review.
• O'Brien S, Kantarjian H, Beran M, Smith T, Koller C, Estey E, Robertson LE, Lerner S, Keating M. Results of fludarabine and prednisone therapy in 264 patients with chronic lymphocytic leukemia with multivariate analysis-derived prognostic model for response to treatment. Blood. 1993 Sep 15;82(6):1695-700.
• Pérez-Simón JA, Kottaridis PD, Martino R, Craddock C, Caballero D, Chopra R, García-Conde J, Milligan DW, Schey S, Urbano-Ispizua A, Parker A, Leon A, Yong K, Sureda A, Hunter A, Sierra J, Goldstone AH, Linch DC, San Miguel JF, Mackinnon S; Spanish and United Kingdom Collaborative Groups for Nonmyeloablative Transplantation. Nonmyeloablative transplantation with or without alemtuzumab: comparison between 2 prospective studies in patients with lymphoproliferative disorders. Blood. 2002 Nov 1;100(9):3121-7.
• Porter DL, Connors JM, Van Deerlin VM, Duffy KM, McGarigle C, Saidman SL, Leonard DG, Antin JH. Graft-versus-tumor induction with donor leukocyte infusions as primary therapy for patients with malignancies. J Clin Oncol. 1999 Apr;17(4):1234.
• Shaw BE, Peggs K, Bird JM, Cavenagh J, Hunter A, Alejandro Madrigal J, Russell NH, Sirohi B, Towlson K, Williams CD, Marks DI; Clinical Trials Committee of the British Society of Blood and Marrow Transplantation. The outcome of unrelated donor stem cell transplantation for patients with multiple myeloma. Br J Haematol. 2003 Dec;123(5):886-95.
• Sierra J, Storer B, Hansen JA, Martin PJ, Petersdorf EW, Woolfrey A, Matthews D, Sanders JE, Storb R, Appelbaum FR, Anasetti C. Unrelated donor marrow transplantation for acute myeloid leukemia: an update of the Seattle experience. Bone Marrow Transplant. 2000 Aug;26(4):397-404.
• Sorror ML, Maris MB, Storer B, Sandmaier BM, Diaconescu R, Flowers C, Maloney DG, Storb R. Comparing morbidity and mortality of HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative and myeloablative conditioning: influence of pretransplantation comorbidities. Blood. 2004 Aug 15;104(4):961-8. Epub 2004 Apr 27.
• Sullivan KM, Weiden PL, Storb R, Witherspoon RP, Fefer A, Fisher L, Buckner CD, Anasetti C, Appelbaum FR, Badger C, et al. Influence of acute and chronic graft-versus-host disease on relapse and survival after bone marrow transplantation from HLA-identical siblings as treatment of acute and chronic leukemia. Blood. 1989 May 1;73(6):1720-8. Erratum in: Blood 1989 Aug 15;74(3):1180.
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• Responsible Party: Northside Hospital, Inc.
• ClinicalTrials.gov Identifier: NCT00818961
• Other Study ID Numbers: CDR0000630617; BMTGG-NSH-756
• First Posted: Jan 8, 2009
• Last Update Posted: Dec 18, 2013
• Last Verified: Oct 1, 2013

• Keywords provided by Northside Hospital, Inc.: accelerated phase chronic myelogenous leukemia; adult acute lymphoblastic leukemia in remission; adult acute myeloid leukemia in remission; adult AML with 11q23 (MLL) abnormalities; blastic phase chronic myelogenous leukemia; chronic myelomonocytic leukemia; chronic phase chronic myelogenous leukemia; prolymphocytic leukemia; recurrent adult T-cell leukemia/lymphoma; refractory chronic lymphocytic leukemia; relapsing chronic myelogenous leukemia; secondary acute myeloid leukemia; stage I adult T-cell leukemia/lymphoma; stage I chronic lymphocytic leukemia; stage II adult T-cell leukemia/lymphoma; stage II chronic lymphocytic leukemia; stage III adult T-cell leukemia/lymphoma; stage III chronic lymphocytic leukemia; stage IV adult T-cell leukemia/lymphoma; stage IV chronic lymphocytic leukemia; recurrent adult Hodgkin lymphoma; anaplastic large cell lymphoma; angioimmunoblastic T-cell lymphoma; cutaneous B-cell non-Hodgkin lymphoma; recurrent cutaneous T-cell NHL; stage I cutaneous T-cell NHL; stage II cutaneous T-cell NHL; stage III cutaneous T-cell NHL; stage IV cutaneous T-cell NHL; extranodal marginal zone B-cell lymphoma of mucosal tissue; nodal marginal zone B-cell lymphoma; splenic marginal zone lymphoma; contiguous st II adult diffuse large cell lymphoma; contiguous st II adult diffuse mixed cell lymphoma; contiguous st II adult diffuse sm cleaved cell lymphoma; contiguous st II grade 1 follicular lymphoma; contiguous st II grade 2 follicular lymphoma; contiguous st II grade 3 follicular lymphoma; contiguous st II mantle cell lymphoma; contiguous st II marginal zone lymphoma; contiguous st II small lymphocytic lymphoma; stage I adult diffuse large cell lymphoma; stage I adult diffuse mixed cell lymphoma; stage I adult diffuse small cleaved cell lymphoma; stage I grade 1 follicular lymphoma; stage I grade 2 follicular lymphoma; stage I grade 3 follicular lymphoma; stage I mantle cell lymphoma; stage I marginal zone lymphoma; stage I small lymphocytic lymphoma; noncontiguous st II adult diffuse large cell lymphoma; noncontiguous st II adult diffuse mixed cell lymphoma; noncontiguous st II adult diffuse sm cleaved cell lymphoma; noncontiguous st II grade 1 follicular lymphoma; noncontiguous st II grade 2 follicular lymphoma; noncontiguous st II grade 3 follicular lymphoma; noncontiguous st II mantle cell lymphoma; noncontiguous st II marginal zone lymphoma; noncontiguous st II small lymphocytic lymphoma; stage III adult diffuse large cell lymphoma; stage III adult diffuse mixed cell lymphoma; stage III adult diffuse small cleaved cell lymphoma; stage III grade 1 follicular lymphoma; stage III grade 2 follicular lymphoma; stage III grade 3 follicular lymphoma; stage III mantle cell lymphoma; stage III marginal zone lymphoma; stage III small lymphocytic lymphoma; stage IV adult diffuse large cell lymphoma; stage IV adult diffuse mixed cell lymphoma; stage IV adult diffuse small cleaved cell lymphoma; stage IV grade 1 follicular lymphoma; stage IV grade 2 follicular lymphoma; stage IV grade 3 follicular lymphoma; stage IV mantle cell lymphoma; stage IV marginal zone lymphoma; stage IV small lymphocytic lymphoma; recurrent adult diffuse large cell lymphoma; recurrent adult diffuse mixed cell lymphoma; recurrent adult diffuse small cleaved cell lymphoma; recurrent adult gr III lymphomatoid granulomatosis; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; recurrent mantle cell lymphoma; recurrent marginal zone lymphoma; recurrent small lymphocytic lymphoma; de novo MDS; previously treated MDS; secondary myelodysplastic syndromes; Waldenstrom macroglobulinemia; myelodysplastic/myeloproliferative disease
• Additional relevant MeSH terms: Lymphoma; Leukemia; Preleukemia; Myelodysplastic Syndromes; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Cyclophosphamide; Busulfan; Rituximab; Methotrexate; Fludarabine; Fludarabine phosphate; Alemtuzumab; Tacrolimus

Study Results

Participant Flow

Recruitment Details	The first patient on this study was enrolled & transplanted on 6/9/05. The last patient on this study was enrolled & transplanted on 1/5/11.
Pre-assignment Detail	No "groups" were assigned. Pts received chemotherapy based on their disease. 39 patients consented to study but 36 patients received protocol treatment. 3 patients were considered screen failures and did not move forward on study.

Arm/Group Title	Hematopoietic Stem Cell Transplantation
Arm/Group Description	All patients receive a hematopoietic stem cell transplant using one of two chemotherapy regimens based on disease type
Period Title: Overall Study
STARTED	36
COMPLETED	36
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Hematopoietic Stem Cell Transplantation
Arm/Group Description	All patients receive a hematopoietic stem cell transplant using one of two chemotherapy regimens based on disease type
Overall Participants	36
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	33 91.7%
>=65 years	3 8.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.44 (6.92)
Sex: Female, Male (Count of Participants)
Female	14 38.9%
Male	22 61.1%
Region of Enrollment (participants) [Number]
United States	36 100%

Outcome Measures

1. Primary Outcome

Title	Survival at Day 100
Description	Survival at Day 100
Time Frame	100 day

Outcome Measure Data

Analysis Population Description

36 patients underwent hematopoietic stem cell transplant and therefore were eligible for evaluation of overall survival at 100 days

Arm/Group Title	Hematopoietic Stem Cell Transplantation
Arm/Group Description	All patients receive a hematopoietic stem cell transplant using one of two chemotherapy regimens based on disease type
Measure Participants	36
Number [participants]	35 97.2%

2. Secondary Outcome

Title	Overall Survival at 1 Year
Description	Evaluation of overall survival at 1 year (# of patients who are alive at 1 year post-transplant)
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

36 patients underwent hematopoietic stem cell transplant and therefore were eligible for evaluation of overall survival at one year post-transplant

Arm/Group Title	Hematopoietic Stem Cell Transplantation
Arm/Group Description	All patients receive a hematopoietic stem cell transplant using one of two chemotherapy regimens based on disease type
Measure Participants	36
Number [participants]	26 72.2%

3. Secondary Outcome

Title	Non-relapse Mortality at Day 100
Description	patients are evaluable for their cause of death at Day 100
Time Frame	Day 100

Outcome Measure Data

Analysis Population Description

36 patients underwent hematopoietic stem cell transplant and therefore were eligible for evaluation of non-relapse mortality at Day 100

Arm/Group Title	Hematopoietic Stem Cell Transplantation
Arm/Group Description	All patients receive a hematopoietic stem cell transplant using one of two chemotherapy regimens based on disease type
Measure Participants	36
Number [participants]	1 2.8%

4. Secondary Outcome

Title	Non-relapse Mortality at 1 Year Post-transplant
Description	Number of patients who died of non-relapse causes at one year. this is in clusive of all patients who were transplanted on study even though only 10 patients died at by 1 year time point. This outcome will be referenced in the donor chimerism outcome. Only 26/36 patients were eligible for this time point as that is all that were alive.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

36 patients underwent hematopoietic stem cell transplant. 10 patients died prior to 1 year post-transplant and were eligible for evaluation of non-relapse mortality at 1 year post-transplant

Arm/Group Title	Hematopoietic Stem Cell Transplantation
Arm/Group Description	All patients receive a hematopoietic stem cell transplant using one of two chemotherapy regimens based on disease type
Measure Participants	36
Number [participants]	4 11.1%

5. Secondary Outcome

Title	Complete Donor Chimerism
Description	Complete donor chimerism (defined as >/= 95% donor cells in peripheral blood CD3+ and CD33+ was measured.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

36 patients underwent hematopoietic stem cell transplant and therefore were eligible for evaluation of donor chimerism

Arm/Group Title	Hematopoietic Stem Cell Transplantation
Arm/Group Description	All patients receive a hematopoietic stem cell transplant using one of two chemotherapy regimens based on disease type
Measure Participants	36
Number [participants]	26 72.2%

6. Secondary Outcome

Title	Neutrophil Recovery
Description	The number of patients experiencing neutrophil recovery post transplant
Time Frame	Day 100

Outcome Measure Data

Analysis Population Description

36 patients underwent hematopoietic stem cell transplant and therefore were eligible for evaluation of neutrophil recovery

Arm/Group Title	Hematopoietic Stem Cell Transplantation
Arm/Group Description	All patients receive a hematopoietic stem cell transplant using one of two chemotherapy regimens based on disease type
Measure Participants	36
Number [participants]	35 97.2%

7. Secondary Outcome

Title	Platelet Engraftment
Description	The number of patients experiencing platelet engraftment post-transplant
Time Frame	Day 100

Outcome Measure Data

Analysis Population Description

36 patients underwent hematopoietic stem cell transplant and therefore were eligible for evaluation of platelet engraftment.

Arm/Group Title	Hematopoietic Stem Cell Transplantation
Arm/Group Description	All patients receive a hematopoietic stem cell transplant using one of two chemotherapy regimens based on disease type
Measure Participants	36
Number [participants]	35 97.2%

8. Secondary Outcome

Title	Number of Patients Requiring the Use of Donor Leukocyte Infusion (DLI) for Early Mixed T-cell Chimerism
Description	DLI is used for patients with mixed chimerism following transplant
Time Frame	Day 100

Outcome Measure Data

Analysis Population Description

36 patients underwent hematopoietic stem cell transplant and therefore were eligible for donor leukocyte infusions for mixed chimerism following transplant

Arm/Group Title	Hematopoietic Stem Cell Transplantation
Arm/Group Description	All patients receive a hematopoietic stem cell transplant using one of two chemotherapy regimens based on disease type
Measure Participants	36
Number [participants]	19 52.8%

9. Secondary Outcome

Title	Number of Patients Experiencing Grade 2-4 Acute Graft-versus-host Disease Post-transplant
Description	patients experiencing acute graft versus host disease post-transplant
Time Frame	patients were followed for 2 years

Outcome Measure Data

Analysis Population Description

36 patients underwent hematopoietic stem cell transplant and therefore were eligible for evaluation of acute graft versus host disease post-transplant.

Arm/Group Title	Hematopoietic Stem Cell Transplantation
Arm/Group Description	All patients receive a hematopoietic stem cell transplant using one of two chemotherapy regimens based on disease type
Measure Participants	36
Number [participants]	15 41.7%

10. Secondary Outcome

Title	Number of Patients Experiencing Chronic Graft Versus Host Disease
Time Frame	>100 days post-transplant

Outcome Measure Data

Analysis Population Description

35 patients survive past 100 days post-transplant and therefore were eligible for evaluation of chronic graft versus host disease

Arm/Group Title	Hematopoietic Stem Cell Transplantation
Arm/Group Description	All patients receive a hematopoietic stem cell transplant using one of two chemotherapy regimens based on disease type
Measure Participants	35
Number [participants]	20 55.6%

11. Secondary Outcome

Title	Number of Patients Experiencing Veno-occlusive Disease (VOD) Post-transplant
Description	Patients will be evaluated up to 4 years post transplant
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

36 patients underwent hematopoietic stem cell transplant and therefore were eligible for evaluation of VOD post-transplant

Arm/Group Title	Hematopoietic Stem Cell Transplantation
Arm/Group Description	All patients receive a hematopoietic stem cell transplant using one of two chemotherapy regimens based on disease type
Measure Participants	36
Number [participants]	0 0%

Adverse Events

Arm/Group Title	Hematopoietic Stem Cell Transplantation
Arm/Group Description	All patients received a hematopoietic Stem Cell Transplantation as part of this clinical trial.
All Cause Mortality
	Hematopoietic Stem Cell Transplantation
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Hematopoietic Stem Cell Transplantation
	Affected / at Risk (%)	# Events
Total	10/36 (27.8%)
Blood and lymphatic system disorders
Thrombotic thrombocytopenic purpura	1/36 (2.8%)	1
Cardiac disorders
aortic valve endocarditis	1/36 (2.8%)	1
General disorders
pulmonary/upper respiratory chest pain	1/36 (2.8%)	1
Infections and infestations
norovirus	1/36 (2.8%)	1
Musculoskeletal and connective tissue disorders
Arthritis	1/36 (2.8%)	1
Nervous system disorders
Syncopal Episode	1/36 (2.8%)	1
Renal and urinary disorders
progressive non-oliguric renal failure	1/36 (2.8%)	1
Respiratory, thoracic and mediastinal disorders
pneumonia	1/36 (2.8%)	1
Vascular disorders
cerebral venous thrombosis and hemorrhage	1/36 (2.8%)	1
thrombosis/embolism	1/36 (2.8%)	1
Other (Not Including Serious) Adverse Events
	Hematopoietic Stem Cell Transplantation
	Affected / at Risk (%)	# Events
Total	36/36 (100%)
Blood and lymphatic system disorders
ANC	29/36 (80.6%)	29
anemia	27/36 (75%)	27
edema	9/36 (25%)	9
fluid overload	2/36 (5.6%)	2
fluid retention	2/36 (5.6%)	2
lower extremity edema	11/36 (30.6%)	11
platelet reaction	2/36 (5.6%)	2
PTT	2/36 (5.6%)	2
thrombocytopenia	31/36 (86.1%)	31
WBC	31/36 (86.1%)	31
Cardiac disorders
bradycardi	2/36 (5.6%)	2
hypertension	21/36 (58.3%)	21
hypotension	15/36 (41.7%)	15
tachycardia	17/36 (47.2%)	17
Ear and labyrinth disorders
ear congestion	3/36 (8.3%)	3
ear pain	3/36 (8.3%)	3
Endocrine disorders
hypothyroidism	3/36 (8.3%)	3
steroid induced diabetes	4/36 (11.1%)	4
Eye disorders
blurry vision	5/36 (13.9%)	5
conjunctivitis	2/36 (5.6%)	2
dry eyes	7/36 (19.4%)	7
periorbital edema	3/36 (8.3%)	3
visual changes	3/36 (8.3%)	3
watery eyes	2/36 (5.6%)	2
Gastrointestinal disorders
abdominal cramping	12/36 (33.3%)	12
abdominal discomfort/tenderness	9/36 (25%)	9
abdominal pain	16/36 (44.4%)	16
bloody stool	2/36 (5.6%)	2
cholecystitis	2/36 (5.6%)	2
constipation	15/36 (41.7%)	15
diarrhea	34/36 (94.4%)	34
difficulty swallowing	6/36 (16.7%)	6
dry heaves	2/36 (5.6%)	2
dry mouth	8/36 (22.2%)	8
dyspepsia	11/36 (30.6%)	11
esophagitis	2/36 (5.6%)	2
gas pain	2/36 (5.6%)	2
gastritis	2/36 (5.6%)	2
GERD	17/36 (47.2%)	17
GI distress	7/36 (19.4%)	7
hemorrhoids	6/36 (16.7%)	6
incontinent (stool)	4/36 (11.1%)	4
mouth erythema	2/36 (5.6%)	2
mouth pain/tenderness	5/36 (13.9%)	5
mucositis	21/36 (58.3%)	21
nausea	33/36 (91.7%)	33
rectal bleeding	3/36 (8.3%)	3
rectal pain/discomfort	4/36 (11.1%)	4
sore throat	15/36 (41.7%)	15
taste alterations	9/36 (25%)	9
tonsillar adenopathy	2/36 (5.6%)	2
vomitting	27/36 (75%)	27
General disorders
abdominal distention	2/36 (5.6%)	2
chest pain	7/36 (19.4%)	7
chest tightness	6/36 (16.7%)	6
dizziness/lighheadedness	17/36 (47.2%)	17
drowsiness	9/36 (25%)	9
epistaxis	12/36 (33.3%)	12
facial drooping	2/36 (5.6%)	2
facial swelling	3/36 (8.3%)	3
fatigue	31/36 (86.1%)	31
feeling "cold"	2/36 (5.6%)	2
fever	29/36 (80.6%)	29
flank pain	2/36 (5.6%)	2
FLUSHING	2/36 (5.6%)	2
headache/migraine	26/36 (72.2%)	26
increased thirst	2/36 (5.6%)	2
lip sore	2/36 (5.6%)	2
loss of balance	4/36 (11.1%)	4
malaise	4/36 (11.1%)	4
neutropenic fever	4/36 (11.1%)	4
pain	8/36 (22.2%)	8
rigors	5/36 (13.9%)	5
scratchy throat	2/36 (5.6%)	2
shaky	2/36 (5.6%)	2
somnolence	3/36 (8.3%)	3
swelling of the neck	2/36 (5.6%)	2
swelling of upper extremities	2/36 (5.6%)	2
syncope	3/36 (8.3%)	3
tremors	10/36 (27.8%)	10
unsteady gait/balance	3/36 (8.3%)	3
Hepatobiliary disorders
ALT	26/36 (72.2%)	26
AST	30/36 (83.3%)	30
hyperbilirubinemia	11/36 (30.6%)	11
Immune system disorders
gout	3/36 (8.3%)	3
Infections and infestations
C diff	4/36 (11.1%)	4
citrobacteria infection	2/36 (5.6%)	2
CMV	18/36 (50%)	18
gram positive bacteremia	2/36 (5.6%)	2
hand foot syndrome	3/36 (8.3%)	3
hsv	3/36 (8.3%)	3
MRSE	8/36 (22.2%)	8
parainfluenza	6/36 (16.7%)	6
pneumonia	5/36 (13.9%)	5
staph bacteremia	2/36 (5.6%)	2
VRE	3/36 (8.3%)	3
Injury, poisoning and procedural complications
fall	2/36 (5.6%)	2
Investigations
Alkaline Phosphatase	22/36 (61.1%)	22
chills	18/36 (50%)	18
night sweats	5/36 (13.9%)	5
Metabolism and nutrition disorders
anorexia	15/36 (41.7%)	15
increased creatinine	29/36 (80.6%)	29
decreased appetite	19/36 (52.8%)	19
decreased oral intake	3/36 (8.3%)	3
dehydration	6/36 (16.7%)	6
diaphoresis	2/36 (5.6%)	2
hypercalcemia	11/36 (30.6%)	11
hyperglycemia	30/36 (83.3%)	30
hyperkalemia	18/36 (50%)	18
hypermagnesemia	7/36 (19.4%)	7
hypernatremia	12/36 (33.3%)	12
hyperphosphatemia	2/36 (5.6%)	2
hypoalbuminemia	28/36 (77.8%)	28
hypocalemia	25/36 (69.4%)	25
hypoglycemia	3/36 (8.3%)	3
hypokalemia	23/36 (63.9%)	23
hypomagnesemia	30/36 (83.3%)	30
hyponatremia	25/36 (69.4%)	25
hypophosphatemia	3/36 (8.3%)	3
weight loss	7/36 (19.4%)	7
Musculoskeletal and connective tissue disorders
ankle pain	7/36 (19.4%)	7
back pain	9/36 (25%)	9
deconditioned	3/36 (8.3%)	3
hip pain	2/36 (5.6%)	2
leg/knee pain	6/36 (16.7%)	6
limited range of motion	2/36 (5.6%)	2
muscle spasm	3/36 (8.3%)	3
myalgia/arthralgia	9/36 (25%)	9
neck pain	4/36 (11.1%)	4
shoulder discomfort/pain	7/36 (19.4%)	7
steroid myopathy	2/36 (5.6%)	2
upper extremity weakness	2/36 (5.6%)	2
weakness	19/36 (52.8%)	19
Nervous system disorders
memory changes	2/36 (5.6%)	2
peripheral neuropathy	11/36 (30.6%)	11
Psychiatric disorders
aggitation	2/36 (5.6%)	2
anxiety	25/36 (69.4%)	25
confusion	6/36 (16.7%)	6
depression	12/36 (33.3%)	12
disoriented	3/36 (8.3%)	3
flat affect	4/36 (11.1%)	4
hallucinations	2/36 (5.6%)	2
insomnia	18/36 (50%)	18
Renal and urinary disorders
BK virus	6/36 (16.7%)	6
dysuria	4/36 (11.1%)	4
hematuria	5/36 (13.9%)	5
nocturia	2/36 (5.6%)	2
renal failure	2/36 (5.6%)	2
renal insufficiency	9/36 (25%)	9
urinary frequency	10/36 (27.8%)	10
urinary hesitancy	3/36 (8.3%)	3
urinary incontinence	5/36 (13.9%)	5
urinary retention	2/36 (5.6%)	2
urinary urgency	5/36 (13.9%)	5
Reproductive system and breast disorders
BPH	2/36 (5.6%)	2
Respiratory, thoracic and mediastinal disorders
basilar crackles	2/36 (5.6%)	2
cough	25/36 (69.4%)	25
diminished breath sounds	5/36 (13.9%)	5
dyspenea on exertion	5/36 (13.9%)	5
hemoptysis	2/36 (5.6%)	2
hypoxia	8/36 (22.2%)	8
nasal congestion	6/36 (16.7%)	6
pneumonitis	2/36 (5.6%)	2
post nasal drip	6/36 (16.7%)	6
pulmonary infiltrates	2/36 (5.6%)	2
pulmonary nodules	3/36 (8.3%)	3
respiratory distress	2/36 (5.6%)	2
respiratory failure	4/36 (11.1%)	4
rhinorrhea	8/36 (22.2%)	8
seasonal allergies	9/36 (25%)	9
shortness of breath	6/36 (16.7%)	6
sinus congestion	9/36 (25%)	9
sinus drainage	5/36 (13.9%)	5
sinus pressure	3/36 (8.3%)	3
sinus thickening	2/36 (5.6%)	2
sinusitis	7/36 (19.4%)	7
URI	2/36 (5.6%)	2
wheezing	5/36 (13.9%)	5
Skin and subcutaneous tissue disorders
anal/rectal erythema	2/36 (5.6%)	2
bruising	10/36 (27.8%)	10
CVC drainage	2/36 (5.6%)	2
CVC pain/tenderness	6/36 (16.7%)	6
dry skin	11/36 (30.6%)	11
eczema	2/36 (5.6%)	2
erythema	5/36 (13.9%)	5
erythema at CVC site	2/36 (5.6%)	2
facial redness	3/36 (8.3%)	3
FOLLICULITIS	2/36 (5.6%)	2
FUNGAL RASH	3/36 (8.3%)	3
pale skin	2/36 (5.6%)	2
PICC line erythema	2/36 (5.6%)	2
pruritis	26/36 (72.2%)	26
rash	26/36 (72.2%)	26
skin abrasion	2/36 (5.6%)	2
skin erythema	2/36 (5.6%)	2
skin hyperpigmentation	2/36 (5.6%)	2
skin wound	2/36 (5.6%)	2
shortness of breath with exertion	3/36 (8.3%)	3
swelling at CVC	2/36 (5.6%)	2
Vascular disorders
DVT	2/36 (5.6%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.