AzTrials
AzTrials

Adult Acute Myeloid Leukemia With 11q23 (MLL) AbnormalitiesPhase 2NCT00040846

Alemtuzumab, Fludarabine Phosphate, and Low-Dose Total Body Irradiation Before Donor Stem Cell Transplantation in Treating Patients With Hematological Malignancies

A Phase 2 study testing alemtuzumab, fludarabine phosphate and total-body irradiation in people with Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities and Adult Acute Myeloid Leukemia With Del(5q), run by Fred Hutchinson Cancer Center at 7 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

This phase II trial studies the side effects and the best dose of alemtuzumab when given together with fludarabine phosphate and low-dose total body irradiation (TBI) and how well it works before donor stem cell transplant in treating patients with hematological malignancies. Read more about this study

Who is it for?
Ages Up to 74 years
What is being tested?
alemtuzumab, fludarabine phosphate and total-body irradiation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
7 sitesin 2 countries
Study dates
Nov 2001to Dec 2009
Phase
Phase 2

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 Up to 74 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Patients must be not eligible for conventional transplants and must have disease expected to be stable for at least 100 days without chemotherapy; patients with hematologic malignancies treatable with hematopoietic stem cell transplant (HSCT) or with a B cell malignancy except those treatable with autologous transplant will be included
  • Aggressive non-Hodgkin lymphomas (NHLs) and Other Histologies Such as Diffuse large B cell NHL
  • Patients with primary refractory or relapsed disease not eligible for an autologous transplant
  • Patients are eligible following an autologous transplant in remission or in relapse
  • Planned tandem transplant is allowed for patients at high risk of relapse
  • Low grade NHL with < 6 months duration of complete remission (CR) between courses of conventional therapy
Show all 25Show fewer
  • Mantle Cell NHL may be treated in first CR
  • Chronic lymphocytic leukemia (CLL) - Must have failed 2 lines of conventional therapy and be refractory to fludarabine
  • Hodgkin disease (HD) - Must have received and failed frontline therapy; patients must have had a prior autologous transplant or were not eligible for autologous transplant; planned tandem transplants are allowed for patients at high risk of relapse
  • Multiple myeloma (MM) - Must have received prior chemotherapy and a prior autologous transplant, unless autologous transplant was not possible; planned tandem transplants are allowed for patients at high risk of relapse
  • Acute myeloid leukemia (AML) - Must have < 5% marrow blasts at the time of transplant
  • Acute lymphocytic leukemia (ALL) - Must have < 5% blasts at the time of transplant
  • Chronic myeloid leukemia (CML) - Patients will be accepted beyond chronic phase 1 (CP1) if they have received previous myelosuppressive chemotherapy or HSCT, and have < 5% marrow blasts at time of transplant
  • Myelodysplastic (MDS)/Myeloproliferative disorders - Must have failed previous myelosuppressive chemotherapy or HSCT, and have < 5% marrow blasts at time of transplant
  • Waldenstrom's Macroglobulinemia - Must have failed 2 courses of therapy
  • Patients < 12 years old must be approved by the Fred Hutchinson Cancer Research Center (FHCRC) principal investigator (PI)
  • Patients who refuse to be treated on a conventional transplant protocol; for this inclusion, criteria transplants must be approved by both the participating institution´s patient review committee such as the Patient Care Conference (PCC) at the FHCRC and the FHCRC principal investigator
  • Patients with related or unrelated donors for whom
  • The best available match is a HLA class II DRB1 and DQB1 matched donor incompatible for any single serologically detectable class I HLA-A, -B, -C mismatch; one additional allele level class I mismatch is allowed OR any combination of 2 allele level mismatches (if typed at the molecular level)
  • There is a likelihood of rapid disease progression while HLA typing and results of a preliminary search and the donor pool suggests that a 10/10 HLA-A, B, C, DRB1 and DQB1 matched unrelated donor will not be found
  • There is no HLA-A, -B or -C one locus allelic mismatched related donor available
  • There is no indication for an autologous transplantation as a treatment option
  • DONOR: Related or unrelated donors who are matched for HLA-DRB1 and DQB1 alleles (must be defined by high resolution typing), and who are mismatched for:
  • Any single serologically detectable HLA-A or B or C antigen +/- 1 allele or
  • Any combination of two HLA-A, -B, or -C alleles (if prospectively typed at molecular level)

Who cannot join

  • Patients who are homozygous at the mismatched major histocompatibility complex (MHC) class I locus
  • A positive cross-match exists between the donor and recipient
  • Patients with rapidly progressive intermediate or high grade NHL
  • Presence of circulating leukemic blasts (in the peripheral blood) detected by standard pathology for patients with AML, ALL or CML
  • Life expectancy severely limited by diseases other than malignancy
  • Central nervous system (CNS) involvement with disease refractory to intrathecal chemotherapy
Show all 22Show fewer
  • Fertile men or women unwilling to use contraceptives during and for up to 12 months post treatment
  • Female patients who are pregnant or breast-feeding
  • Human immunodeficiency virus (HIV) positive patients
  • Patients with active non-hematologic malignancies (except non-melanoma skin cancers)
  • Patients with a history of non-hematologic malignancies (except non-melanoma skin cancers) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a > 20% risk of disease recurrence
  • Fungal infections with radiological progression after receipt of amphotericin B or active triazole for greater than 1 month
  • Patients with active bacterial or fungal infections unresponsive to medical therapy
  • Patients with the following organ dysfunction symptomatic coronary artery disease or ejection fraction < 35% or other cardiac failure requiring therapy; ejection fraction is required if the patient is > 50 years of age, or history of cardiac disease or anthracycline exposure
  • Diffusion capacity of carbon monoxide (DLCO) < 35%; total lung capacity (TLC) < 35%; or forced expiratory volume in one second (FEV1) < 35% and/or receiving supplementary continuous oxygen
  • Patients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function, bridging fibrosis, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure; cirrhosis of the liver with evidence of portal hypertension; alcoholic hepatitis; esophageal varices; a history of bleeding esophageal varices; hepatic encephalopathy; uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time; ascites related to portal hypertension; bacterial or fungal liver abscess; biliary obstruction; chronic viral hepatitis with total serum bilirubin >3 mg/dL; or symptomatic biliary disease
  • Patients with poorly controlled hypertension on multiple antihypertensives
  • Karnofsky score < 70 for adult patients
  • Lansky-Play Performance Score < 50 for pediatric patients
  • DONOR: Bone marrow (BM) donors
  • DONOR: Donors who are HIV-positive and/or, medical conditions that would result in increased risk for granulocyte colony-stimulating factor (G-CSF) mobilization and harvest of peripheral blood stem cell (PBSC)
  • DONOR: Donors < 12 years of age

Trial locations and contacts

7 sites in 2 countries.

7 sites in 2 countries

United States6 sites

  • Presbyterian - Saint Lukes Medical Center - Health One

    Denver, Colorado, 80218

  • Froedtert Memorial Lutheran Hospital, Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

  • LDS Hospital

    Salt Lake City, Utah, 84143

  • VA Puget Sound Health Care System

    Seattle, Washington, 98101

  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

Italy1 site

  • University of Torino

    Torino, 10126

Other trials in Italy

About this study

Official title: Campath® [Alemtuzumab] Dose Escalation, Low-Dose TBI and Fludarabine Followed by HLA Class I Mismatched Donor Stem Cell Transplantation for Patients With Hematologic Malignancies - A Multi-Center Trial

This phase II trial studies the side effects and the best dose of alemtuzumab when given together with fludarabine phosphate and low-dose total body irradiation (TBI) and how well it works before donor stem cell transplant in treating patients with hematological malignancies. Giving chemotherapy and low-dose TBI before a donor peripheral blood 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. Also, monoclonal antibodies, such as alemtuzumab, can find cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine (CSP) and mycophenolate mofetil (MMF) after transplant may stop this from happening.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine whether stable allogeneic engraftment from related and unrelated human leukocyte antigen (HLA)-mismatched stem cell donors can be safely established using a non-myeloablative conditioning regimen plus escalating doses of the anti-CD52 monoclonal antibody (mAb) Campath (alemtuzumab) in patients with hematologic malignancies.

SECONDARY OBJECTIVES:

  1. Evaluate the risk of occurrence of acute and chronic graft-vs-host disease (GVHD).

II. Evaluate the risk/incidence of infections.

III. Determine whether engraftment can be maintained with a single dose fludarabine, donor lymphocyte infusion (DLI) and continued MMF/CSP.

IV. Evaluate the risk for disease progression and relapse.

OUTLINE: This is a dose-escalation study of alemtuzumab.

CONDITIONING REGIMEN: Patients receive alemtuzumab intravenously (IV) over 2 hours on days -8 to -5 and fludarabine phosphate IV on days -4 to -2. Patients also undergo low-dose TBI on day 0.

HEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT): Patients undergo allogeneic peripheral blood stem cell transplantation on day 0.

IMMUNOSUPPRESSION: Patients receive CSP IV or orally (PO) twice daily (BID) on days -3 to 180 with taper to day 365 and MMF PO thrice daily (TID) on days 0-100 with taper to day 156.

After completion of study treatment, patients are followed up periodically.

Being tested
alemtuzumab, fludarabine phosphate, total-body irradiation, allogeneic hematopoietic stem cell transplantation, peripheral blood stem cell transplantation
Medical subject headings
Congenital Abnormalities, Lymphoma, Extranodal NK-T-Cell, Lymphoma, Large-Cell, Anaplastic, Immunoblastic Lymphadenopathy, Burkitt Lymphoma, Lymphoma, Large B-Cell, Diffuse, Leukemia, Myeloid, Chronic-Phase, Myeloproliferative Disorders

What participants receive

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

  • alemtuzumabBiological

    Also called anti-CD52 monoclonal antibody, Campath-1H, MoAb CD52, Monoclonal Antibody Campath-1H

    Given IV

  • fludarabine phosphateDrug

    Also called 2-F-ara-AMP, Beneflur, Fludara

    Given IV

  • total-body irradiationRadiation

    Also called TBI

    Undergo TBI

  • allogeneic hematopoietic stem cell transplantationProcedure or surgery

    Undergo allogeneic HSCT

  • peripheral blood stem cell transplantationProcedure or surgery

    Also called PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell

    Undergo allogeneic peripheral blood stem cell transplantation

  • mycophenolate mofetilDrug

    Also called Cellcept, MMF

    Given PO

  • cyclosporineDrug

    Also called ciclosporin, cyclosporin, cyclosporin A, CYSP

    Given IV or PO

Study groups in NCT00040846
Study groupRoleWhat they receive
Treatment (dose-escalation of alemtuzumab, HSCT)ExperimentalCONDITIONING REGIMEN: Patients receive alemtuzumab IV over 2 hours on days -8 to -5 and fludarabine phosphate IV on days -4 to -2. Patients also undergo low-dose TBI on day 0. HSCT: Patients undergo allogeneic peripheral blood stem cell transplantation on day 0. IMMUNOSUPPRESSION: Patients receive CSP IV or PO BID on days -3 to 180 with taper to day 365 and MMF PO TID on days 0-100, with taper to day 156.
Receives: Biological: alemtuzumab; Drug: fludarabine phosphate; Radiation: total-body irradiation; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Drug: mycophenolate mofetil; Drug: cyclosporine

What is being measured

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

  1. Evaluate the Risk of Transplant Related Mortality.

    Percentage patients with Day 100 transplant related mortality.

    Measured: 100 days after transplant

  2. Evaluate the Risk of Occurrence of Acute and Chronic GVHD

    Percentage patients who developed acute/chronic GVHD.

    aGVHD Stages

    Skin:

    1. a maculopapular eruption involving < 25% BSA
    2. a maculopapular eruption involving 25 - 50% BSA
    3. generalized erythroderma
    4. generalized erythroderma with bullous formation and often with desquamation

    Liver:

    1. bilirubin 2.0 - 3.0 mg/100 mL
    2. bilirubin 3 - 5.9 mg/100 mL
    3. bilirubin 6 - 14.9 mg/100 mL
    4. bilirubin > 15 mg/100 mL

    Gut:

    Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients with visible bloody diarrhea are at least stage 2 gut and grade 3 overall.

    aGVHD Grades Grade III: Stage 2 - 4 gastrointestinal involvement and/or +2 to +4 liver involvement, with or without a rash Grade IV: Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death

    Measured: 1 year after transplant

  3. Determine Whether Engraftment Can be Maintained With a Single Dose Fludarabine, DLI and Continued MMF/CSP, Defined as Rejection Rate < 20%.

    Mixed chimerism will be defined as the detection of donor T cells (CD3+) and granulocytes (CD 33+), as a proportion of the total T cell and granulocyte population, respectively, of greater than 5% and less than 95% in the peripheral blood. Full donor chimerism is defined as > 95% donor CD3+ T cells.

    Measured: 100 days after transplant

Secondary outcomes (2)

  1. Evaluate the Risk/Incidence of Infections

    Percentage patients who experienced infections within 100 days post-transplant.

    Measured: 100 days after transplant

  2. Evaluate the Risk for Disease Progression and Relapse

    Percentage patients who relapsed/progressed within 1 year post-transplant.

    Measured: 1 year after transplant

Timeline

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

  1. First posted27 Jan 2003 (estimated)
  2. Study startNov 2001
  3. Primary completionDec 2009
  4. Study completionDec 2009

Resources

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
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00040846
Sponsor's protocol ID
1591.00
Other IDs
NCI-2011-00471, 1591.00, P30CA015704, P01CA018029
Status last verified
Jan 2020
First submitted
8 Jul 2002
Last updated
29 Jan 2020
Data monitoring committee
Yes

Publications

  • Nakamae H, Storer BE, Storb R, Storek J, Chauncey TR, Pulsipher MA, Petersen FB, Wade JC, Maris MB, Bruno B, Panse J, Petersdorf E, Woolfrey A, Maloney DG, Sandmaier BM. Low-dose total body irradiation and fludarabine conditioning for HLA class I-mismatched donor stem cell transplantation and immunologic recovery in patients with hematologic malignancies: a multicenter trial. Biol Blood Marrow Transplant. 2010 Mar;16(3):384-94. doi: 10.1016/j.bbmt.2009.11.004. Epub 2009 Nov 10.

    PubMed 19900571

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in