Cyclosporine Plus Methotrexate or Alemtuzumab

December 28, 2017 updated by: Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea

Randomized Trial of Cyclosporine + CAMPATH-1H (ALEMTUZUMAB) vs. Cyclosporine + METHOTREXATE in Patients Diagnosed With Mature B-cell Neoplasms - Chronic Lymphocytic Leukemia and Low-grade Lymphomas - Receiving Allogeneic Hematopoietic Stem Cell Transplantation With Nonmyeloablative Conditioning Regimen

The primary aim of the study was to compare the efficacy of the procedure in terms of event-free survival between patients receiving cyclosporine (CsA) plus either alemtuzumab (CAMPATH-1H ) or methotrexate (MTX) after matched related donor allo-reduced intensity conditioning. Secondary aims were: 1. To compare the incidence of infections and transplant-related mortality between the two arms; 2. to compare the incidence of acute and chronic GVHD 3. to evaluate hematologic and immunologic reconstitution and evolution of chimerism and residual disease.

Patients were randomly assigned to received cyclosporine plus alemtuzumab or cyclosporine plus MTX and were stratified according to diagnosis: Chronic lymphocytic leukemia or Low grade- non-Hodgkin's lymphoma.

All patients received the same reduced-intensity conditioning (RIC) scheme based on fludarabine 150mg/m2 (30 mg/m2/day everyday from -8 to -4) plus melphalan 140mg/m2 (70 mg/m2/day everyday from -3 to -2). Regarding the GVHD prophylaxis, patients in group 1 (n=17) received CsA 1 mg/kg intravenously starting on day -7 and 2/mg/Kg from day -1 plus alemtuzumab administered at a dose of 20 mg IV on -8 to -4 whereas in group 2 (n=23) pts received CsA at same doses as group 1 plus MTX given at a dose of 15 mg/m2 intravenously on days 1 and 10 mg/m2 on days 3, 6 and 11, followed by folinic acid rescue (15 mg in +1 and 10 mg in +3, +6 and +11 intravenously every 6 hours for 4 doses starting 24 hours after each dose of MTX).

Acute and chronic GVHD were similarly graded by established criteria [20, 21]. In patients receiving alemtuzumab, CsA was suspended by day +130. They also received donor lymphocyte infusion (DLI) at a dose of 1 x 107 cluster of differentiation 3 / kg on day +180 in case of active disease, persistence of minimal residual disease detected by flow cytometry or mixed chimerism and no GVHD. In case mixed chimerism, donor lymphocyte infusion was performed if patient hematopoiesis progressively increased. In patients receiving CsA + MTX, CsA was suspended by day +180. These patients received DLI only in situations specified above.

The statistical analysis has been designed to identify a 20% difference in terms of disease-free survival (based on the increased incidence of relapse in patients receiving T-cell depletion).

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

72

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Poland
      • Gdansk, Poland
        • Department of Propedeutic Oncology, Medical University of Gdansk
  • Spain
      • Barcelona, Spain
        • Hospital Clinic I Provincial
      • Barcelona, Spain
        • Santa Creu i Sant Pau Hospital
      • Salamanca, Spain
        • Hospital Universitario de Salamanca
    • Barcelona
      • Badalona, Barcelona, Spain
        • Clinical Hematology Department. ICO-Hospital Germans Trias i Pujol. Jose Carreras Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

45 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria:

  1. Having an identical Human Leukocyte Antigens (HLA) or a mismatched family donor.
  2. Age between 45 and 65 years (outside this age range at the discretion of each center).

  3. Indications:

    • Follicular lymphoma with one of the following characteristics:

      1. Poor prognosis follicular NHL (3 or more factors by Federico et al: erythrocyte sedimentation rate (ESR)> 30, male,> 60 years, high LDH> 2 extranodal areas, pathologic stage (PS) >2 or The International Prognostic Index (IPI) 3 or high lactate dehydrogenase (LDH) or micro Beta 2) failing to achieve CR with regimens including fludarabine and anti CD20 (cluster of differentiation antigen 20 ).
      2. 2nd CR (complete response) or PR (partial response) not candidates for autologous transplantation;
      3. persistent disease or relapse after autologous transplantation.

    • Other low-grade lymphomas:

      1. relapsed after autologous transplantation.
      2. autologous transplant candidates which can not be performed because of the inability to collect a sufficient number of cells, steam cells disease persistence, etc..

    • Chronic lymphocytic leukemia with one of the following characteristics:

      1. "B" symptoms: weight loss >10% in the last 6 months, fever >38ºC (degrees centigrade) for 14 days without infection, night sweats without infection
      2. lymphadenopathy >10 cm or progressive, progressive splenomegaly
      3. Anemia and/or thrombocytopenia secondary to bone marrow infiltration
      4. Diffuse lymphocytic infiltration of the bone marrow
      5. Progressive lymphocytosis (>50% in 2 months) or a lymphocyte doubling time <12 months Any of the above criteria is an inclusion criteria in the protocol in patients who have received at least one line of treatment including fludarabine
      6. Patients with poor prognostic cytogenetic abnormalities: 17p-, 11q-with VDJ unmutated

  4. Patients must also meet the following general requirements:

    1. Performance status <3 (Zubrod score, Eastern Cooperative Oncology Group (ECOG) performance status or WHO (World Health Organization) )
    2. forced expiratory volume at one second (FEV1) > 39%, lung diffusing capacity for carbon monoxide (DLCO) and forced vital capacity (FVC) > 39% of the theoretical values
    3. Total bilirubin and transaminases <3 x the normal maximum value, unless attributable to base haemopathy
    4. Creatinine <2 x normal maximum and clearance> 40 mL / min unless attributable to his base haemopathy
    5. No evidence of symptomatic disease, cirrhosis or active hepatitis
    6. Negative serology for HIV
    7. Written informed consent

Exclusion criteria:

  1. Impaired hepatic or renal function superior to that described above
  2. Presence of serious diseases that prevent chemotherapy treatments
  3. Presence of psychiatric comorbidity
  4. HIV infection
  5. Other prior neoplasm
  6. Do not have signed informed consent
  7. Pregnant or at risk of pregnancy by inadequate contraceptive measures.
  8. Patients diagnosed with chronic lymphocytic leukemia (CLL) transformation to more aggressive cytologic or histologic forms (prolymphocytic leukemia, large cell lymphoma, Hodgkin's disease) and those affected with autoimmune hemolytic anemia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Cyclosporine + METHOTREXATE
MTX days +1, +3, +6 and +11 followed by folinic acid rescue. All patients will receive CSA from day -7.
Drug: Cyclosporine + METHOTREXATE
MTX days +1, +3, +6 and +11 followed by rescue with folinic Ac. All patients receive CSA from day -7.
Experimental: Cyclosporine + CAMPATH-1H
CAMPATH-1H at a dose of 20 mg / day at 8-hour intravenous infusion on days -8 to -4. All patients will receive CSA from day -7.
Drug: Cyclosporine + CAMPATH-1H
CAMPATH-1H at a dose of 20 mg / day at 8-hour intravenous infusion on days -8 to -4. All patients will receive CSA from day -7.
Other Names:
  • Alemtuzumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy of transplantation in terms of event-free survival
Time Frame: From +270 days
To compare the efficacy of transplantation in terms of event-free survival between patients receiving CAMPATH-1H or methotrexate in allogeneic related donor with nonmyeloablative conditioning.
From +270 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of infections and transplant-related mortality
Time Frame: 1 year
Compare the incidence of infections and transplant-related mortality between the two arms
1 year

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
incidence of graft versus host disease
Time Frame: 5 years
Analyze the impact on the incidence of graft versus host disease (GVHD) acute and chronic CAMPATH-1H + DLI compared with MTX as GVHD prophylaxis in allogeneic related donor with nonmyeloablative conditioning.
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea

Investigators

  • Principal Investigator: José Antonio Pérez-Simón, MD, PhD, University of Salamanca

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2003

Primary Completion (Actual)

November 1, 2009

Study Completion (Actual)

November 1, 2009

Study Registration Dates

First Submitted

March 12, 2015

First Submitted That Met QC Criteria

March 2, 2016

First Posted (Estimate)

March 8, 2016

Study Record Updates

Last Update Posted (Actual)

December 29, 2017

Last Update Submitted That Met QC Criteria

December 28, 2017

Last Verified

December 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TIRCAMPATH-alo 2002

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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