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Bone Marrow FailurePhase 2/3NCT01019876

Risk-Adapted Allogeneic Stem Cell Transplantation For Mixed Donor Chimerism In Patients With Non-Malignant Diseases

A Phase 2/3 study testing Fludarabine, Cyclophosphamide and Busulfan in people with Bone Marrow Failure and Osteopetrosis, run by Columbia University 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
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Trial summary

This study proposes the use of a reduced intensity chemotherapy/radiation therapy regimen followed by stem cell transplantation, as compared to standard ablative chemotherapy regimens associated with stem cell transplantation, in a population of patients with non-malignant diseases (non-cancer). Read more about this study

Who is it for?
Ages Up to 30 years
Conditions the study is for
Bone Marrow Failure, Osteopetrosis, Fanconi Anemia
What is being tested?
Fludarabine, Cyclophosphamide and Busulfan
Could I receive a placebo?
No, everyone receives an active treatment
How many people
38 participants
Where
1 siteUnited States
Study dates
Sep 2002to 7 Sep 2021
Phase
Phase 2/3
Are there results?
None posted in the registry

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 30 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Patients must meet the eligibility criteria for organ function regardless of diagnosis:
  • Age < 30 or = 30 years of age
  • Adequate renal function defined as serum creatinine < or = 1.5 x normal, or creatinine clearance or radioisotope glomerular filtration rate (GFR) > or =40 ml/min/m2 or >60 ml/min/1.73 m2 or an equivalent GFR as determined by the institutional normal range
  • Adequate liver function defined as serum glutamic oxaloacetic transaminase (SGOT)(Aspartate transaminase (AST)) or serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase (ALT)) < 5.0 x normal
  • Adequate cardiac function defined as shortening fraction of > or = 28% by echocardiogram, or ejection fraction of > or = 48% by radionuclide angiogram or echocardiogram
  • Adequate pulmonary function defined as asymptomatic or, if symptomatic, carbon monoxide diffusing capacity test (DLCO) >45% of predicted (corrected for hemoglobin level). If unable to obtain pulmonary function test, O2 saturation >85% in room air.
Show all 53Show fewer
  • Bone Marrow Failure Syndromes
  • Patients with the following diagnoses are eligible:
  • Severe Aplastic Anemia:
  • Hypocellular bone marrow biopsy (<25% cellularity) and 2/3 of the following (at diagnosis or nadir):
  • Absolute Neutrophil Count (ANC) <200/mm3,
  • Platelets <20,000/mm3
  • Reticulocyte count <60,000/mm3
  • Fanconi Anemia:
  • Abnormal clastogenic studies (all patients) Severe Congenital Neutropenia (Kostmann's Syndrome) Amegakaryocytic Thrombocytopenia
  • Severe thrombocytopenia (< or =20,000/mm3) at diagnosis
  • Severe depletion of megakaryocytes on bone marrow aspirate (< or =25% normal)
  • Diamond-Blackfan Anemia:
  • Corticosteroid dependent for > 6 months OR Transfusion dependent OR refractory acquired pure red cell aplasia.
  • Infantile Osteopetrosis Schwachman-Diamond Syndrome Dyskeratosis Congenita Other bone marrow failure syndromes at discretion of co-principal investigators All BM failure patients must have BM bx within 2 weeks prior to starting therapy to confirm disease status
  • Immunodeficiencies:
  • SCIDS, all subtypes
  • Combined Immunodeficiency Syndrome
  • Wiskott-Aldrich Syndrome
  • Chronic Granulomatous Disease
  • Chediak-Higashi Syndrome
  • Leukocyte Adhesion Deficiency
  • Other immunodeficiencies at discretion of co-principal investigators
  • Inborn Errors of Metabolism (IEOM):
  • Transplant is recommended for the following disorders:
  • Hurler syndrome (alpha-L-iduronidase deficiency, MPS-I), preferably before age 24 months
  • Maroteaux-Lamy syndrome (galactosamine-4-sulfatase deficiency,MPSVI)
  • Sly syndrome (beta-glucuronidase deficiency, MPS-VII)
  • Globoid cell leukodystrophy (galactocerebrosidase deficiency), with careful attention to neurologic status in the infantile form
  • Metachromatic leukodystrophy (arylsulfatase A deficiency),juvenile or adult onset form; late infantile MLD only if pre-symptomatic
  • Childhood-onset X-linked adrenoleukodystrophy (X-ALD), at initial signs of neuropsychological deterioration, with dietary modification prior to transplant
  • Fucosidosis (fucosidase deficiency)
  • Mannosidosis
  • Aspartylglucosaminuria
  • Niemann-Pick Disease Type B (acid sphingomyelinase deficiency)
  • Other diagnoses may be considered at the discretion of the co-principal investigators
  • Transplant is not recommended for Hunter syndrome (iduronate sulfatase deficiency), Sanfilippo syndrome Type A (heparan N-sulfatase deficiency), Sanfilippo syndrome Type B (-N-acetyl-transferase deficiency), Sanfilippo syndrome Type C (-acetyltransferase deficiency), Sanfilippo syndrome Type D (-acetylglucosamine-6-sulfatase deficiency), Morquio syndrome (galactose-6-sulfatase deficiency); or Niemann-Pick disease Type A or C.
  • For X-ALD patients greater than 5 years of age, IQ >80 is required. For other patients greater than 5 years of age, IQ > 70 is required.
  • For patients less than 5 years of age, the developmental quotient or clinical neurodevelopmental examination should demonstrate potential for stabilization at a level of functioning where continuous life support (e.g. mechanical ventilation) would not be predicted to be required in the year following transplantation.
  • For Gaucher disease (glucocerebrosidase deficiency) Type I (non-neuropathic), the primary therapy is enzyme replacement, but allogeneic stem cell transplant has been used effectively.
  • Histiocytoses:
  • Hemophagocytic Lymphohistiocytosis (HLH)
  • Familial Erythrophagocytic Lymphohistiocytosis
  • Langerhans Cell Histiocytosis
  • Patients with multi-system disease whose initial disease is stable or progressive after minimum 6 weeks of appropriate therapy, OR patients with recurrent multi-system disease.
  • Malignant Histiocytosis
  • All histiocytic patients must have BM bx within 2 weeks prior to starting therapy to confirm disease status
  • Other non-malignant diseases not listed above may be eligible if deemed appropriate by the co-principal investigators.

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Columbia University Medical Center

    New York, New York, 10032

Other trials in United States

About this study

Official title: Risk-Adapted Allogeneic Stem Cell Transplantation For Mixed Donor Chimerism In Patients With Selected Non-Malignant Diseases

This study proposes the use of a reduced intensity chemotherapy/radiation therapy regimen followed by stem cell transplantation, as compared to standard ablative chemotherapy regimens associated with stem cell transplantation, in a population of patients with non-malignant diseases (non-cancer). Eligible patients will have a non-malignant disease in one of the following four strata: bone marrow failure syndromes, immunodeficiencies, inborn errors of metabolism, or histiocytoses. Patients will be assigned to therapy according to diagnosis. Patients will be stratified by disease into one of four strata and treatment regimens will be based on specific disease criteria and conditions. Although these diseases are non-malignant in name, they are often malignant by nature of the disease progression, treatment and associated complications.

Read the detailed description

This treatment program proposes the use of a reduced intensity chemotherapy regimen, which has been shown to be effective for inducing remission and cure in these diseases. Studies have shown that the use of non-myeloablative chemotherapy regimens have resulted in 75-100% engraftment (replacement of the recipient bone marrow with the donor bone marrow), and significantly reduced transplant related complications as compared to the standard myeloablative chemotherapy regimens.

Being tested
Fludarabine, Cyclophosphamide, Busulfan, Alemtuzumab, Rabbit Anti-thymocyte Globulin
Keywords
Bone marrow Failure, Fanconi Anemia, Severe Combined Immunodeficiency, Osteopetrosis, Allogeneic Stem Cell Transplantation, Chemotherapy, Radiation Therapy
Medical subject headings
Bone Marrow Failure Disorders, Osteopetrosis, Fanconi Anemia, Severe Combined Immunodeficiency

What participants receive

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

  • FludarabineDrug

    Also called Fludara®

  • CyclophosphamideDrug

    Also called Cytoxan®

  • BusulfanDrug

    Also called Busulfex®

  • AlemtuzumabDrug

    Also called Campath®

  • Rabbit Anti-thymocyte GlobulinDrug

    Also called TMG, Thymoglobulin

  • Horse Anti-thymocyte GlobulinDrug

    Also called ATG, Lymphocyte Immune Globulin

Study groups in NCT01019876
Study groupRoleWhat they receive
Regimen A - Standard Conditioning RegimenActive comparatorStandard conditioning regimen for all diseases except those diseases or conditions noted in Regimen B, C and D: * Fludarabine (180 mg/m2 total dose) * Busulfan (16 mg/kg less than or equal to 4 yrs and 12.8 mg/ kg >4 yrs total dose) * Alemtuzumab (2mg/m2 x 1day, 6mg/m2 x 2 days, 20mg/m2 x 2days)
Receives: Drug: Fludarabine; Drug: Busulfan; Drug: Alemtuzumab
Regimen BExperimentalIncludes patients with a diagnosis of: Osteopetrosis and Severe Aplastic Anemia with a history of >10 blood transfusions, or Blackfan-Diamond's anemia, or Chronic Granulomatous Disease, or Wiskott Aldrich Syndrome: * Cyclophosphamide (200 mg/kg total dose) * Fludabarine (180 mg/m2 total dose) * Rabbit Anti-thymocyte Globulin (8mg/kg total dose)
Receives: Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Rabbit Anti-thymocyte Globulin
Regimen CExperimentalIncludes patients with any one of the following specific diagnosis: Fanconi Anemia, Dyskeratosis Congenita or Schwachman Diamond Syndrome * Cyclophosphamide (40 mg/kg total dose) * Fludarabine (140 mg/m2 total dose) * Anti-Thymocyte Globulin (horse) (150mg/kg total dose)/TBI 450 cGy
Receives: Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Horse Anti-thymocyte Globulin
Regimen DExperimentalIncludes patients with the following specific diagnosis of: Severe Combined Immune Deficiency Syndrome with no evidence of host NK function (will receive Regimen A) and matched related donor * Cyclophosphamide (30 mg/kg total dose) * Fludarabine (90 mg/m2 total dose) * Rabbit anti-thymocyte globulin (Thymoglobulin)(TMG)**(8 mg/kg total dose) TMG only in family haploidentical and unrelated donors
Receives: Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Rabbit Anti-thymocyte Globulin

What is being measured

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

  1. Number of participants with Adverse Events

    The number of participants with adverse events as assessed by National Cancer Institute (NCI) Common Terminology Criteria Adverse Events (CTCAE - Version 4.0)

    Measured: Up to 2 years

Secondary outcomes (4)

  1. Risk of disease progression

    To determine the risk of disease progression (including neuropsychological deterioration in patients with metabolic non-malignant diseases) following a Flu/CY or Bu/Flu based conditioning regimen.

    Measured: Up to 1 year

  2. Immune reconstitution

    Titers of immune cells (T cells, B cells, and NK cells) from peripheral blood will be measured following a Flu/CY or Bu/Flu based conditioning regimen and AlloSCT in patients with selected non-malignant diseases.

    Measured: Up to 1 year

  3. Incidence of graft versus host disease (GVHD)

    Incidence of GVHD in participants following a Flu/Cy or Bu/Flu based conditioning regimen.

    Measured: Up to 1 year

  4. Metabolic/Immune reconstitution

    To determine metabolic/immune (gene/protein) reconstitution by standard biochemical/PCR assays in patients.

    Measured: Up to 1 year

Timeline

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

  1. First posted25 Nov 2009 (estimated)
  2. Study startSep 2002
  3. Primary completion7 Sep 2021
  4. Study completion7 Sep 2021

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 2/3
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
38 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01019876
Sponsor's protocol ID
AAAB0170
Other IDs
CHNY-01-509
Status last verified
Oct 2024
First submitted
23 Nov 2009
Last updated
31 Oct 2024
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Fludarabine, Cyclophosphamide and Busulfan in people with Bone Marrow Failure and Osteopetrosis, run by Columbia University 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 53 inclusion and 0 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 31 Oct 2024. 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 combined 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.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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 Adverse Events (time frame: Up to 2 years). 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 NCT01019876.

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 31 Oct 2024.

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