LeukemiaPhase 2NCT00818961

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

A Phase 2 study testing alemtuzumab, graft-versus-tumor induction therapy and rituximab in people with Leukemia and Lymphoma, run by Northside Hospital, Inc. at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 40 to 72 years
Conditions the study is for: Leukemia, Lymphoma, Myelodysplastic Syndromes
What is being tested?: alemtuzumab, graft-versus-tumor induction therapy and rituximab
Type of treatment: Pill or oral medicine, Injection or infusion, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 36 participants
Where: 1 siteUnited States
Study dates: May 2005to Mar 2012
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 40 to 72 years
All sexes
No healthy volunteers
Adult, Older adult

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)

Trial locations and contacts

1 site in 1 country.

United States1 site

Blood and Marrow Transplant Group of Georgia
Atlanta, Georgia, 30342

Other trials in United States

About this study

Official title: Reduced Intensity Allogeneic Stem Cell Transplantation With Matched Unrelated Donors for Patients With Hematologic Malignancies

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.

Read the 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.

Conditions: Leukemia, Lymphoma, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases
Being tested: alemtuzumab, graft-versus-tumor induction therapy, rituximab, busulfan, cyclophosphamide
Keywords: 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
Medical subject headings: Leukemia, Lymphoma, Myelodysplastic Syndromes, Myelodysplastic-Myeloproliferative Diseases, Leukemia, Myeloid, Accelerated Phase, Congenital Abnormalities, Blast Crisis, Leukemia, Myelomonocytic, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

alemtuzumabBiological
Also called Campath
43 mg subcutaneously over 3 days (3 mg on day -11, 10 mg on day -10, 30 mg on day -9)
graft-versus-tumor induction therapyBiological
curative potential of allogeneic transplant results from the immune anti-tumor effect of donor cells or GVT/GVL
rituximabBiological
Also called Rituxan
in patients with Cd20+ malignancies: rituximab 375 mg/m*2 day -13. rituximab 1000 mg/m*2 on days, -6, +1, +8.
busulfanDrug
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.
cyclophosphamideDrug
Also called Cytoxan
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
fludarabine phosphateDrug
Also called Fludara
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.
methotrexateDrug
5 mg/m2 administered on days +1, +3 and +6
tacrolimusDrug
Also called Prograf; FK506
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
allogeneic bone marrow transplantationProcedure or surgery
Also called HSCT, allo transplant
Recipients will receive an allogeneic transplant on day 0 after receiving high-dose chemotherapy. This trial uses matched unrelated donor stem cells.

Study groups in NCT00818961
Study group	Role	What they receive
Hematopoietic Stem Cell Transplantation	Other	All patients receive a hematopoietic stem cell transplant using one of two chemotherapy regimens based on donor type Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

Survival at Day 100
Survival at Day 100
Measured: 100 day

Secondary outcomes (10)

Overall Survival at 1 Year
Evaluation of overall survival at 1 year (# of patients who are alive at 1 year post-transplant)
Measured: 1 year
Non-relapse Mortality at Day 100
patients are evaluable for their cause of death at Day 100
Measured: Day 100
Non-relapse Mortality at 1 Year Post-transplant
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.
Measured: 1 year
Complete Donor Chimerism
Complete donor chimerism (defined as >/= 95% donor cells in peripheral blood CD3+ and CD33+ was measured.
Measured: 2 years
Neutrophil Recovery
The number of patients experiencing neutrophil recovery post transplant
Measured: Day 100
Platelet Engraftment
The number of patients experiencing platelet engraftment post-transplant
Measured: Day 100
Number of Patients Requiring the Use of Donor Leukocyte Infusion (DLI) for Early Mixed T-cell Chimerism
DLI is used for patients with mixed chimerism following transplant
Measured: Day 100
Number of Patients Experiencing Grade 2-4 Acute Graft-versus-host Disease Post-transplant
patients experiencing acute graft versus host disease post-transplant
Measured: patients were followed for 2 years
Number of Patients Experiencing Chronic Graft Versus Host Disease
Measured: >100 days post-transplant
Number of Patients Experiencing Veno-occlusive Disease (VOD) Post-transplant
Patients will be evaluated up to 4 years post transplant
Measured: 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2005Mar 2012

First posted8 Jan 2009 (estimated)
Study startMay 2005
Primary completionMar 2011
Study completionMar 2012

Why it stopped: terminated early due to meeting end point with fewer patients than anticipated

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (23)Papers the sponsor has linked to this study.
Other trials for LeukemiaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 36 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00818961
Sponsor's protocol ID: CDR0000630617
Other IDs: BMTGG-NSH-756
Status last verified: Oct 2013
First submitted: 7 Jan 2009
Last updated: 18 Dec 2013
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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.
PubMed 10733488
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. doi: 10.1038/sj.bmt.1702519.
PubMed 10982286
Weisdorf DJ, Billett AL, Hannan P, Ritz J, Sallan SE, Steinbuch M, Ramsay NK. Autologous versus unrelated donor allogeneic marrow transplantation for acute lymphoblastic leukemia. Blood. 1997 Oct 15;90(8):2962-8.
PubMed 9376576
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. doi: 10.1046/j.1365-2141.1996.4811022.x.
PubMed 8611476
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. doi: 10.1182/blood-2003-03-0937. Epub 2003 Nov 6.
PubMed 14604976
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. doi: 10.1046/j.1365-2141.2003.04714.x.
PubMed 14632780
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.
PubMed 11110679
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. doi: 10.1056/NEJM199804023381405.
PubMed 9521984
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. doi: 10.1182/blood-2004-02-0545. Epub 2004 Apr 27.
PubMed 15113759
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.
PubMed 2653460
Mehta J, Singhal S. Graft-versus-myeloma. Bone Marrow Transplant. 1998 Nov;22(9):835-43. doi: 10.1038/sj.bmt.1701459.
PubMed 9827810
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.
PubMed 1991174
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. doi: 10.1200/JCO.1999.17.4.1234.
PubMed 10561184
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.
PubMed 8400226
Giralt S, Estey E, Albitar M, van Besien K, Rondon G, Anderlini P, O'Brien S, Khouri I, Gajewski J, Mehra R, Claxton D, Andersson B, Beran M, Przepiorka D, Koller C, Kornblau S, Korbling 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.
PubMed 9192777

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 18 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Reduced Intensity Allogeneic Stem Cell Transplantation With Matched Unrelated Donors for Patients With Hematologic Malignancies
ClinicalTrials.gov ID: NCT00818961
Acronym / sponsor ID: CDR0000630617
Conditions: Leukemia, Lymphoma, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases
Keywords: 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
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: terminated early due to meeting end point with fewer patients than anticipated
Enrolment: 36 participants (actual)
Lead sponsor: Northside Hospital, Inc.University, hospital or other
Collaborators: Blood and Marrow Transplant Group of Georgia
Study start: May 2005
Primary completion: Mar 2011 (actual)
Study completion: Mar 2012 (actual)
First posted: 8 Jan 2009 (estimated)
Results: Posted 18 Dec 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

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

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Hematopoietic Stem Cell Transplantation	Other	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 transplantationAll patients receive a hematopoietic stem cell transplant using one of two chemotherapy regimens based on donor type

Who may qualify

Ages: 40 to 72 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
alemtuzumabAlso: Campath43 mg subcutaneously over 3 days (3 mg on day -11, 10 mg on day -10, 30 mg on day -9)	Biological	Hematopoietic Stem Cell Transplantation
graft-versus-tumor induction therapycurative potential of allogeneic transplant results from the immune anti-tumor effect of donor cells or GVT/GVL	Biological	Hematopoietic Stem Cell Transplantation
rituximabAlso: Rituxanin patients with Cd20+ malignancies: rituximab 375 mg/m2 day -13. rituximab 1000 mg/m2 on days, -6, +1, +8.	Biological	Hematopoietic Stem Cell Transplantation
busulfanFor 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	Hematopoietic Stem Cell Transplantation
cyclophosphamideAlso: Cytoxan750 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	Drug	Hematopoietic Stem Cell Transplantation
fludarabine phosphateAlso: FludaraFor 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.	Drug	Hematopoietic Stem Cell Transplantation
methotrexate5 mg/m2 administered on days +1, +3 and +6	Drug	Hematopoietic Stem Cell Transplantation
tacrolimusAlso: Prograf; FK5060.03mg/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	Drug	Hematopoietic Stem Cell Transplantation
allogeneic bone marrow transplantationAlso: HSCT, allo transplantRecipients will receive an allogeneic transplant on day 0 after receiving high-dose chemotherapy. This trial uses matched unrelated donor stem cells.	Procedure or surgery	Hematopoietic Stem Cell Transplantation

Primary outcome

Survival at Day 100
Time frame: 100 day
Survival at Day 100

10 secondary outcomes

Overall Survival at 1 Year
Time frame: 1 year
Non-relapse Mortality at Day 100
Time frame: Day 100
Non-relapse Mortality at 1 Year Post-transplant
Time frame: 1 year
Complete Donor Chimerism
Time frame: 2 years
Neutrophil Recovery
Time frame: Day 100
Platelet Engraftment
Time frame: Day 100
Number of Patients Requiring the Use of Donor Leukocyte Infusion (DLI) for Early Mixed T-cell Chimerism
Time frame: Day 100
Number of Patients Experiencing Grade 2-4 Acute Graft-versus-host Disease Post-transplant
Time frame: patients were followed for 2 years
Number of Patients Experiencing Chronic Graft Versus Host Disease
Time frame: >100 days post-transplant
Number of Patients Experiencing Veno-occlusive Disease (VOD) Post-transplant
Time frame: 4 years

Results and safety

Results posted to the registry on 18 Dec 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Hematopoietic Stem Cell Transplantation	36	36

Primary outcome: Survival at Day 100

Time frame: 100 day. Number. Unit: participants

Measure	Hematopoietic Stem Cell Transplantation n = 36
Value	35

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

10 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Hematopoietic Stem Cell Transplantation	10 of 36 (27.8%)	36 of 36 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2013.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 10733488McGlave 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.
Background: PubMed 10982286Sierra 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. doi: 10.1038/sj.bmt.1702519.
Background: PubMed 9376576Weisdorf DJ, Billett AL, Hannan P, Ritz J, Sallan SE, Steinbuch M, Ramsay NK. Autologous versus unrelated donor allogeneic marrow transplantation for acute lymphoblastic leukemia. Blood. 1997 Oct 15;90(8):2962-8.
Background: PubMed 8611476Anderson 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. doi: 10.1046/j.1365-2141.1996.4811022.x.
Background: PubMed 14604976Izutsu 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. doi: 10.1182/blood-2003-03-0937. Epub 2003 Nov 6.
Background: PubMed 14632780Shaw 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. doi: 10.1046/j.1365-2141.2003.04714.x.
Background: PubMed 11110679Davies 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.
Background: PubMed 9521984Hansen 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. doi: 10.1056/NEJM199804023381405.
Background: PubMed 15113759Sorror 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. doi: 10.1182/blood-2004-02-0545. Epub 2004 Apr 27.
Background: PubMed 2653460Sullivan 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.
Background: PubMed 9827810Mehta J, Singhal S. Graft-versus-myeloma. Bone Marrow Transplant. 1998 Nov;22(9):835-43. doi: 10.1038/sj.bmt.1701459.
Background: PubMed 1991174Jones 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Scott R. Solomon, MD principal investigator

Blood and Marrow Transplant Group of Georgia

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing alemtuzumab, graft-versus-tumor induction therapy and rituximab in people with Leukemia and Lymphoma, run by Northside Hospital, Inc. at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 18 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Dec 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Survival at Day 100 (time frame: 100 day). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00818961, which also lists 23 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2013.