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NCT00195624

Alemtuzumab to Treat Severe Aplastic Anemia

Completed Phase 2 Results posted Last updated 7 July 2020
What this trial tests

Phase 2 trial testing Alemtuzumab (Campath ) in Severe Aplastic Anemia, Refractory in 47 participants. Completed in 15 October 2018.

Timeline
15 September 2005
Primary endpoint
14 April 2014
15 October 2018

Quick facts

Lead sponsorNational Heart, Lung, and Blood Institute (NHLBI)
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment47
Start date15 September 2005
Primary completion14 April 2014
Estimated completion15 October 2018
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Heart, Lung, and Blood Institute (NHLBI)

Who can join

Adults 2 to 110, any sex, with Severe Aplastic Anemia, Refractory or Severe Aplastic Anemia, Relapse. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Hematological Response at 6 Months Primary · 6 months

Hematological response is defined as no longer satisfying blood count criteria for Severe Aplastic Anemia. Patients were classified as responders if they met two of the following three criteria: ANC greater than 500/ mm'; platelet count greater than 20,000/mm3; and reticulocyte count greater than 40,000/mm3 (60,000/mm3 after January 1993).

GroupValue95% CI
Refractory0
Relapsed18

Adverse events — posted to ClinicalTrials.gov

Time frame: 6 months. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Refractory
Serious: 2/5 (40%)
Deaths: 5/5
Relapsed
Serious: 22/42 (52%)
Deaths: 13/42

Serious adverse events (15 terms)

ReactionSystemRefractoryRelapsed
Febrile neutropeniaBlood and lymphatic system disorders
AnaemiaBlood and lymphatic system disorders
Cardiac failureCardiac disorders
PresyncopeCardiac disorders
GastritisGastrointestinal disorders
Gastrointestinal haemorrhageGastrointestinal disorders
Allergic transfusion reactionImmune system disorders
Fungal infectionInfections and infestations
PneumoniaInfections and infestations
Haemorrhagic ovarian cystNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Central nervous system inflammationNervous system disorders
Cerebral ischaemiaNervous system disorders
Vaginal ulcerationReproductive system and breast disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
RashSkin and subcutaneous tissue disorders
Other adverse events (137 terms — click to expand)

ReactionSystemRefractoryRelapsed
Infusion related reactionGeneral disorders
PyrexiaGeneral disorders
ChillsGeneral disorders
LymphopeniaBlood and lymphatic system disorders
FatigueGeneral disorders
ContusionInjury, poisoning and procedural complications
HeadacheNervous system disorders
CoughRespiratory, thoracic and mediastinal disorders
RashSkin and subcutaneous tissue disorders
NauseaGastrointestinal disorders
Rash pruriticSkin and subcutaneous tissue disorders
PetechiaeBlood and lymphatic system disorders
PainGeneral disorders
EcchymosisBlood and lymphatic system disorders
DizzinessCardiac disorders
DyspnoeaCardiac disorders
Abdominal painGastrointestinal disorders
Upper respiratory tract infectionInfections and infestations
Liver function test increasedInvestigations
Gingival bleedingGastrointestinal disorders
Iron overloadInjury, poisoning and procedural complications
VomitingGastrointestinal disorders
Chest discomfortCardiac disorders
Chest painCardiac disorders
DiarrhoeaGastrointestinal disorders
Blood pressure decreasedInvestigations
Back painMusculoskeletal and connective tissue disorders
InsomniaNervous system disorders
Vaginal haemorrhageReproductive system and breast disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
PruritusSkin and subcutaneous tissue disorders
Dyspnoea exertionalCardiac disorders
PalpitationsCardiac disorders
TachycardiaCardiac disorders
Eye painEye disorders
Vision blurredEye disorders
Visual impairmentEye disorders
Dry mouthGastrointestinal disorders
DyspepsiaGastrointestinal disorders
Oropharyngeal painGastrointestinal disorders

Most-reported serious reactions: Febrile neutropenia, Anaemia, Cardiac failure, Presyncope, Gastritis, Gastrointestinal haemorrhage, Allergic transfusion reaction, Fungal infection.

Data from ClinicalTrials.gov NCT00195624 adverse events section.

Sponsor's own description

This study will evaluate the safety and usefulness of a new immunosuppressive drug, alemtuzumab (Campath ), in patients with severe aplastic anemia (SAA). SAA is a rare and serious blood disorder in which the bone marrow stops making red blood cells, white blood cells and platelets. Alemtuzumab is a monoclonal antibody that attaches to and kills white blood cells called lymphocytes. In certain types of aplastic anemia, lymphocytes are responsible for the destruction of stem cells in the bone marrow, leading to a decrease in blood counts. Because alemtuzumab destroys lymphocytes, it may be effective in treating aplastic anemia. Alemtuzumab is currently approved to treat chronic lymphocytic leukemia and is also helpful in other conditions that require immunosuppression, such as rheumatoid arthritis and immune cytopenias. Patients 2 years of age and older with severe aplastic anemia whose disease does not respond to immunosuppressive therapy or has recurred following immunosuppressive therapy may be eligible for this study. Participants undergo the following tests and procedures: * Pretreatment evaluation: Patients have a medical history, physical examination, blood tests, electrocardiogram (EKG), echocardiogram, 24-hour Holter monitor (continuous 24-hour monitoring of electrical activity of the heart), bone marrow biopsy (withdrawal through a needle of a small sample of bone marrow for analysis). * Placement of a central line, if needed: An intravenous line (tube) is placed into a major vein in the patient's chest. It can stay in the body for the entire treatment period and be used to give chemotherapy or other medications, including antibiotics and blood transfusions, if needed, and to withdraw blood samples. * Alemtuzumab therapy: Patients are admitted to the NIH Clinical Center for the first few injections for close monitoring of side effects. After receiving an initial small test dose, patients begin the first of ten daily injections under the skin, each lasting about 2 hours. Once patients tolerate the infusions with minimal or no side effects, they may be given the remaining infusions on an outpatient basis. Patients who relapse after their initial response to alemtuzumab are given cyclosporine to see if this drug will boost their immune response. * Patients receive transfusions, growth factors, and antibiotic therapy, as needed. * Infection therapy: Patients are given aerosolized pentamidine to protect against lung infections and valacyclovir to protect against herpes infections. * A blood test is done and vital signs are measured every day while patients receive alemtuzumab. * Patients have an echocardiogram and 24-hour Holter monitor after the last dose of alemtuzumab. * Blood tests are done weekly for the first 3 months after alemtuzumab administration, then every other week until 6 months. Patients return to the NIH for follow-up visits 1 month, 3 months, 6 months, and yearly for 5 years after the last dose of alemtuzumab for the following tests and evaluations: * Blood test * Repeat echocardiogram at 3-month visit * Repeat bone marrow biopsy 6 months and 12 months after alemtuzumab, then as clinically indicated for 5 years.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Activity of alemtuzumab monotherapy in treatment-naive, relapsed, and refractory severe acquired aplastic anemia.
    Scheinberg P, Nunez O, Weinstein B, Scheinberg P, et al · · 2012 · cited 76× · PMID 22067384 · DOI 10.1182/blood-2011-05-352328
  2. Calcineurin-NFAT signalling in myeloid leucocytes: new prospects and pitfalls in immunosuppressive therapy.
    Bendickova K, Tidu F, Fric J. · · 2017 · cited 52× · PMID 28606994 · DOI 10.15252/emmm.201707698
  3. Predictors of clonal evolution and myeloid neoplasia following immunosuppressive therapy in severe aplastic anemia.
    Groarke EM, Patel BA, Shalhoub R, Gutierrez-Rodrigues F, et al · · 2022 · cited 43× · PMID 35896822 · DOI 10.1038/s41375-022-01636-8
  4. HLA associations, somatic loss of HLA expression, and clinical outcomes in immune aplastic anemia.
    Zaimoku Y, Patel BA, Adams SD, Shalhoub R, et al · · 2021 · cited 42× · PMID 34724566 · DOI 10.1182/blood.2021012895
  5. Allogeneic Bone Marrow-Derived Mesenchymal Stromal Cells Expanded In Vitro for Treatment of Aplastic Anemia: A Multicenter Phase II Trial.
    Pang Y, Xiao HW, Zhang H, Liu ZH, et al · · 2017 · cited 16× · PMID 28504860 · DOI 10.1002/sctm.16-0227
  6. Long-term eltrombopag for bone marrow failure depletes iron.
    Young DJ, Fan X, Groarke EM, Patel B, et al · · 2022 · cited 10× · PMID 35312200 · DOI 10.1002/ajh.26543
  7. Alemtuzumab in relapsed immune severe aplastic anemia: Long-term results of a phase II study.
    Aggarwal N, Manley AL, Shalhoub R, Durrani J, et al · · 2023 · cited 8× · PMID 37021397 · DOI 10.1002/ajh.26924
  8. Abstract Book for the 27th Congress of the European Hematology Association
    · 2022

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