AzTrials
AzTrials

Non Malignant DiseasesPhase 2RICNCT01050855

Reduced Intensity Conditioning (RIC) Regimen for Patients With Non-malignant Disorders

A Phase 2 study testing Reduced-Intensity Conditioning in people with Non Malignant Diseases and Immunodeficiencies, run by Children's Hospital of Philadelphia at 1 site in United States.

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 pilot study evaluates the safety and effectiveness of reduced-intensity conditioning (RIC) regimens prior to allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric and young adult patients with non-malignant disorders, including immunodeficiencies and hemoglobinopathies. Read more about this study

Who is it for?
Ages 6 months to 25 years
What is being tested?
Reduced-Intensity Conditioning
Could I receive a placebo?
No, everyone receives an active treatment
How many people
56 participants
Where
1 siteUnited States
Study dates
Jan 2008to Jun 2025
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 6 months to 25 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Age >6 months- 25 years
  • Diseases eligible for Distal Alemtuzumab:
  • Immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome
  • Sickle cell disease (Neurologic: history of stroke or any neurologic defect lasting >24 hours accompanied by infarct on MRI; or abnormal transcranial Doppler, or abnormal MRI with cerebral vasculature stenosis. OR minimum 2 episodes of acute chest syndrome in preceding 2 year period OR history 3 or more severe pain events/year in the 2 years prior to transplant.)
  • Thalassemia major
  • Bone marrow failure, including Kostmann's, amegakaryocytic thrombocytopenia, Blackfan-Diamond syndrome
Show all 16Show fewer
  • Diseases eligible for Intermediate Alemtuzumab
  • Hemophagocytic lymphohistiocytosis other macrophage activation syndromes, severe Langerhans histiocytosis
  • Severe combined immune deficiency, adenosine deaminase deficiency, common variable immunodeficiency
  • Wiskott-Aldrich syndrome
  • Organ criteria:
  • Cardiac: Echocardiogram shortening fraction >27%
  • Pulmonary: for those with pulmonary function tests: DLCO/VA >40% If DLCO/VA is not reported this is considered inability to perform the test. In this case Pulse Ox and Respiratory Exam will be used as evaluation criteria.
  • Renal: Serum creatinine <1.5 x upper limit of normal for age
  • Hepatic:; ALT and AST <5 x upper limit of normal
  • Infection: No active infections.

Who cannot join

  • Uncontrolled bacterial, fungal or viral infections.
  • Bare lymphocyte syndrome (MHC class II deficiency)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • The Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

This Phase II pilot study evaluates the safety and effectiveness of reduced-intensity conditioning (RIC) regimens prior to allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric and young adult patients with non-malignant disorders, including immunodeficiencies and hemoglobinopathies. The study examines different conditioning approaches that vary in the timing and dosing of alemtuzumab (Campath), as well as disease-specific modifications for beta thalassemia major and infants. The primary objective is to assess donor engraftment and event-free survival at one year following transplant. The study aims to determine whether RIC regimens can reduce toxicity while maintaining successful engraftment and disease control.

Read the detailed description

This Phase II, single-institution, investigator-initiated pilot study evaluates reduced-intensity conditioning (RIC) strategies in the setting of allogeneic hematopoietic stem cell transplantation (HSCT) for non-malignant disorders. The study focuses on optimizing conditioning approaches to balance adequate immunosuppression for donor engraftment with minimization of regimen-related toxicity.

RIC regimens are designed to reduce the organ toxicity and late effects associated with traditional myeloablative conditioning while maintaining sufficient host immune suppression to allow durable donor cell engraftment. This approach is particularly relevant in patients with pre-existing organ dysfunction or increased vulnerability to treatment-related complications. In non-malignant diseases, full donor chimerism may not be required for therapeutic benefit, and stable mixed chimerism may be sufficient for disease correction.

The conditioning strategies evaluated in this protocol primarily differ in the timing and administration of alemtuzumab, an anti-CD52 monoclonal antibody used to deplete host lymphocytes and reduce the risk of graft rejection and graft-versus-host disease. Earlier ("distal") administration is intended to reduce prolonged exposure at the time of stem cell infusion, thereby preserving donor immune function, while more proximal administration provides more immediate immunosuppression but may increase the risk of delayed immune recovery.

Disease-specific modifications to conditioning intensity are incorporated for select populations. Patients with beta thalassemia major receive additional cytoreductive and immunosuppressive agents to address the higher risk of graft rejection associated with intact immunity and expanded marrow space. Infants with immunodeficiencies are treated with modified regimens designed to reduce toxicity while maintaining engraftment potential.

Following conditioning, patients undergo stem cell transplantation using donor sources that may include related or unrelated donors as well as cord blood or alternative donor options based on clinical circumstances. Standard supportive care and post-transplant immunosuppression are administered according to institutional guidelines.

Patients are monitored longitudinally for engraftment, donor chimerism, immune recovery, and transplant-related complications. The study also evaluates clinical management strategies such as donor lymphocyte infusions or second transplantation in cases of declining chimerism or graft failure.

This study is intended to inform optimal conditioning approaches for patients with non-malignant disorders undergoing HSCT, with the goal of improving transplant tolerability while maintaining effective and durable engraftment.

Being tested
Reduced-Intensity Conditioning
Keywords
Non-malignant diseases, Immune deficiencies, Hemoglobinopathies, Reduced Intensity Conditioning(RIC)
Medical subject headings
Immunologic Deficiency Syndromes, Hemoglobinopathies

What participants receive

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

  • Reduced-Intensity ConditioningDrug

    Also called RIC

    A pre-transplant conditioning approach designed to provide sufficient immunosuppression to enable donor cell engraftment while minimizing regimen-related toxicity compared to myeloablative conditioning. Regimens are adapted based on patient age and underlying disease characteristics using the following agents: Campath, Fludarabine, Melphalan, Cyclosporine, Cellcept (MMF).

Study groups in NCT01050855
Study groupRoleWhat they receive
Reduced-Intensity Conditioning (RIC) HSCTExperimentalParticipants receive reduced-intensity conditioning with alemtuzumab-, fludarabine-, and melphalan-based regimens, varying by timing of alemtuzumab (distal or intermediate). Regimens are based on established protocols used in non-malignant disorders. Alemtuzumab is administered prior to other agents to reduce risk of declining donor chimerism. Participants then undergo allogeneic stem cell transplantation with standard post-transplant care.
Receives: Drug: Reduced-Intensity Conditioning

What is being measured

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

  1. Number of Participants With Engraftment

    engraftment of patients with non-malignant disorders will be evaluated using a reduced-intensity conditioning regimen

    Measured: Post Transplant -100 days

Secondary outcomes (1)

  1. Event-free Survival

    Event-free survival is defined as the time interval to either primary or late graft failure, disease recurrence, or death.

    Measured: 1 year post transplant

Timeline

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

  1. First posted18 Jan 2010 (estimated)
  2. Study startJan 2008
  3. Primary completionJul 2024
  4. Study completionJun 2025

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
Model description
This is a single-group assignment study in which all enrolled participants receive reduced-intensity conditioning prior to allogeneic hematopoietic stem cell transplantation. The study evaluates multiple conditioning approaches that vary in the timing and components of the regimen (including alemtuzumab-based strategies and disease-specific modifications), without randomization or comparison to a separate control group. Outcomes are assessed across the entire cohort to evaluate engraftment, tolerability, and feasibility of the RIC approaches.
Masking
None (open label)
Enrolment
56 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01050855
Sponsor's protocol ID
08-005658
Other IDs
CHP 894
Acronym
RIC
Status last verified
Aug 2026
First submitted
15 Jan 2010
Last updated
23 Sep 2026
Data monitoring committee
No
Individual data sharing
No

Publications

  • Kean LS, Durham MM, Adams AB, Hsu LL, Perry JR, Dillehay D, Pearson TC, Waller EK, Larsen CP, Archer DR. A cure for murine sickle cell disease through stable mixed chimerism and tolerance induction after nonmyeloablative conditioning and major histocompatibility complex-mismatched bone marrow transplantation. Blood. 2002 Mar 1;99(5):1840-9. doi: 10.1182/blood.v99.5.1840.

    PubMed 11861303

  • Iannone R, Casella JF, Fuchs EJ, Chen AR, Jones RJ, Woolfrey A, Amylon M, Sullivan KM, Storb RF, Walters MC. Results of minimally toxic nonmyeloablative transplantation in patients with sickle cell anemia and beta-thalassemia. Biol Blood Marrow Transplant. 2003 Aug;9(8):519-28. doi: 10.1016/s1083-8791(03)00192-7.

    PubMed 12931121

  • Fischer A, Landais P, Friedrich W, Morgan G, Gerritsen B, Fasth A, Porta F, Griscelli C, Goldman SF, Levinsky R, et al. European experience of bone-marrow transplantation for severe combined immunodeficiency. Lancet. 1990 Oct 6;336(8719):850-4. doi: 10.1016/0140-6736(90)92348-l.

    PubMed 1976883

  • Friedrich W, Goldmann SF, Vetter U, Fliedner TM, Heymer B, Peter HH, Reisner Y, Kleihauer E. Immunoreconstitution in severe combined immunodeficiency after transplantation of HLA-haploidentical, T-cell-depleted bone marrow. Lancet. 1984 Apr 7;1(8380):761-4. doi: 10.1016/s0140-6736(84)91277-7.

    PubMed 6143084

  • Wildin RS, Smyk-Pearson S, Filipovich AH. Clinical and molecular features of the immunodysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome. J Med Genet. 2002 Aug;39(8):537-45. doi: 10.1136/jmg.39.8.537.

    PubMed 12161590

  • Rao A, Kamani N, Filipovich A, Lee SM, Davies SM, Dalal J, Shenoy S. Successful bone marrow transplantation for IPEX syndrome after reduced-intensity conditioning. Blood. 2007 Jan 1;109(1):383-5. doi: 10.1182/blood-2006-05-025072. Epub 2006 Sep 21.

    PubMed 16990602

  • Klangsinsirikul P, Carter GI, Byrne JL, Hale G, Russell NH. Campath-1G causes rapid depletion of circulating host dendritic cells (DCs) before allogeneic transplantation but does not delay donor DC reconstitution. Blood. 2002 Apr 1;99(7):2586-91. doi: 10.1182/blood.v99.7.2586.

    PubMed 11895797

  • Chakraverty R, Peggs K, Chopra R, Milligan DW, Kottaridis PD, Verfuerth S, Geary J, Thuraisundaram D, Branson K, Chakrabarti S, Mahendra P, Craddock C, Parker A, Hunter A, Hale G, Waldmann H, Williams CD, Yong K, Linch DC, Goldstone AH, Mackinnon S. Limiting transplantation-related mortality following unrelated donor stem cell transplantation by using a nonmyeloablative conditioning regimen. Blood. 2002 Feb 1;99(3):1071-8. doi: 10.1182/blood.v99.3.1071.

    PubMed 11807015

  • Morris EC, Rebello P, Thomson KJ, Peggs KS, Kyriakou C, Goldstone AH, Mackinnon S, Hale G. Pharmacokinetics of alemtuzumab used for in vivo and in vitro T-cell depletion in allogeneic transplantations: relevance for early adoptive immunotherapy and infectious complications. Blood. 2003 Jul 1;102(1):404-6. doi: 10.1182/blood-2002-09-2687. Epub 2003 Mar 6.

    PubMed 12623851

  • Chakrabarti S, Mackinnon S, Chopra R, Kottaridis PD, Peggs K, O'Gorman P, Chakraverty R, Marshall T, Osman H, Mahendra P, Craddock C, Waldmann H, Hale G, Fegan CD, Yong K, Goldstone AH, Linch DC, Milligan DW. High incidence of cytomegalovirus infection after nonmyeloablative stem cell transplantation: potential role of Campath-1H in delaying immune reconstitution. Blood. 2002 Jun 15;99(12):4357-63. doi: 10.1182/blood.v99.12.4357.

    PubMed 12036862

  • Chakrabarti S, Avivi I, Mackinnon S, Ward K, Kottaridis PD, Osman H, Waldmann H, Hale G, Fegan CD, Yong K, Goldstone AH, Linch DC, Milligan DW. Respiratory virus infections in transplant recipients after reduced-intensity conditioning with Campath-1H: high incidence but low mortality. Br J Haematol. 2002 Dec;119(4):1125-32. doi: 10.1046/j.1365-2141.2002.03992.x.

    PubMed 12472597

  • Shah AJ, Kapoor N, Crooks GM, Weinberg KI, Azim HA, Killen R, Kuo L, Rushing T, Kohn DB, Parkman R. The effects of Campath 1H upon graft-versus-host disease, infection, relapse, and immune reconstitution in recipients of pediatric unrelated transplants. Biol Blood Marrow Transplant. 2007 May;13(5):584-93. doi: 10.1016/j.bbmt.2007.01.076. Epub 2007 Mar 23.

    PubMed 17448918

  • Shenoy S, Grossman WJ, DiPersio J, Yu LC, Wilson D, Barnes YJ, Mohanakumar T, Rao A, Hayashi RJ. A novel reduced-intensity stem cell transplant regimen for nonmalignant disorders. Bone Marrow Transplant. 2005 Feb;35(4):345-52. doi: 10.1038/sj.bmt.1704795.

    PubMed 15592491

  • Jacobsohn DA, Duerst R, Tse W, Kletzel M. Reduced intensity haemopoietic stem-cell transplantation for treatment of non-malignant diseases in children. Lancet. 2004 Jul 10-16;364(9429):156-62. doi: 10.1016/S0140-6736(04)16628-2.

    PubMed 15246728

  • Horn B, Baxter-Lowe LA, Englert L, McMillan A, Quinn M, Desantes K, Cowan M. Reduced intensity conditioning using intravenous busulfan, fludarabine and rabbit ATG for children with nonmalignant disorders and CML. Bone Marrow Transplant. 2006 Feb;37(3):263-9. doi: 10.1038/sj.bmt.1705240.

    PubMed 16327813

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Reduced-Intensity Conditioning in people with Non Malignant Diseases and Immunodeficiencies, run by Children's Hospital of Philadelphia 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?

The sponsor lists 16 inclusion and 2 exclusion criteria. 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: finished, as of the sponsor's last update on 23 Sep 2026. 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 21 Jul 2026). 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?

Number of Participants With Engraftment (time frame: Post Transplant -100 days). 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 NCT01050855, which also lists 27 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 23 Sep 2026; AzTrials last refreshed its copy on 6 Nov 2026.

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

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in