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Severe Aplastic AnemiaPhase 2NCT02833805

NMA Haplo or MUD BMT for Newly Diagnosed Severe Aplastic Anemia

A Phase 2 study testing Thymoglobulin, Fludarabine and Cyclophosphamide in people with Severe Aplastic Anemia and Aplastic Anemia, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins 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

Our primary objective is to determine if it is feasible for previously untreated severe aplastic anemia (SAA) patients to be transplanted using non-myeloablative conditioning and post transplantation cyclophosphamide. Read more about this study

Who is it for?
Any age
What is being tested?
Thymoglobulin, Fludarabine and Cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
1 siteUnited States
Study dates
Sep 2016to Jul 2021
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 Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Confirmed diagnosis of inherited or acquired severe aplastic anemia (SAA)
  • One of the following available donors:
  • HLA-haploidentical relative
  • If recipient is >= 40 years old, may use HLA-matched related donor
  • For recipients with inherited bone marrow failure syndromes (IBMFS) with clear evidence of same disorder in potential related donors, may use 10/10 matched unrelated donor
  • Recipient and/or legal guardian must sign protocol informed consent
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  • Donor must be willing to donate bone marrow
  • Left ventricular ejection fraction (LVEF) >= 40%. For recipients < 13 years old, shortening fraction >= 26% may be used instead.
  • Bilirubin < 3 x upper limit of normal (ULN) for age, unless patient has Gilbert's disease
  • aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 5 x ULN for age
  • For patients >= 13 years old: estimated creatinine clearance > 50 mL/min using Cockcroft-Gault formula and actual body weight
  • For patients >= 1 but < 13 years old: glomerular filtration rate (GFR) estimated by updated Schwartz formula >= 90 mL/min/1.73 m^2. If estimated GFR is < 90 mL/min/1.73 m^2, 24-hour measured creatinine clearance must be > 50 mL/min/1.73 m^2.
  • For patients >= 8 years old, diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin) > 40%; forced expiratory volume at one second (FEV1) > 50%; forced vital capacity (FVC) > 50%
  • For patients < 8 years old or unable to undergo pulmonary function testing: no evidence of dyspnea at rest; no need for supplemental oxygen; oxygen saturation > 92% on room air
  • Karnofsky/Lansky status (depending on age) >= 70%
  • Females and males of childbearing potential must agree to practice 2 effective methods of contraception at the same time. If unwilling, they must agree to complete abstinence.

Who cannot join

  • Previous administration of immunosuppressive therapy for SAA.
  • Fanconi anemia. At minimum, this diagnosis must be excluded by diepoxybutane (DEB) or equivalent testing on peripheral blood or marrow in patients < 30 years old.
  • Clonal cytogenetic abnormalities consistent with pre-myelodysplastic syndrome (pre-MDS) or MDS on bone marrow examination
  • Presence of anti-donor antibodies
  • Prior allogeneic stem cell transplant
  • Prior solid organ transplant
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  • Uncontrolled bacterial, viral, or fungal infection
  • HIV seropositivity
  • Active hepatitis B or C infection determined by serology and/or nucleic acid testing (NAT)
  • Pregnancy or active breastfeeding
  • Prior malignancies except: resected basal carcinoma or treated cervical carcinoma in situ; cancer treated with curative intent > 5 years previously. Other prior cancers will not be allowed unless approved by the PI.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Baltimore, Maryland, 21287

Other trials in United States

About this study

Official title: A Phase II Trial of Non-Myeloablative (NMA) Conditioning and Transplantation of Partially HLA-Mismatched/Haploidentical Related or Matched Unrelated Donor (MUD) Bone Marrow for Newly Diagnosed Patients With Severe Aplastic Anemia

Our primary objective is to determine if it is feasible for previously untreated severe aplastic anemia (SAA) patients to be transplanted using non-myeloablative conditioning and post transplantation cyclophosphamide.

Read the detailed description

This is a clinical trial of upfront bone marrow transplantation for patients with SAA who do not have a fully human leukocyte antigen (HLA) matched donor. The trial uses a conditioning regimen which has been successful in the refractory and relapsed setting to maximize engraftment and post transplant therapy to minimize graft versus host disease (GVHD). This would be used here in patients who have not yet undergone immunosuppressive therapy for their SAA or are thought to be unlikely to respond to immunosuppressive therapy for SAA.

Keywords
immunosuppression, nonmyeloablative, non-myeloablative, allogeneic, tacrolimus, bone marrow, bone marrow transplant, cyclophosphamide, thymoglobulin, ATG, fludarabine
Medical subject headings
Anemia, Aplastic, Bone Marrow Failure Disorders

What participants receive

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

  • ThymoglobulinDrug

    Also called Anti-thymocyte globulin, ATG

    Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily

  • FludarabineDrug

    Also called Fludara

    Days -6 through -2: 30 mg/m^2 IV daily

  • CyclophosphamideDrug

    Also called Cytoxan, Cy, CTX

    Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily

  • Total body irradiationRadiation

    Also called TBI

    Day -1: 200 centigray (cGy) in a single fraction

  • TacrolimusDrug

    Also called FK-506, FK506, Prograf

    Start on Day 5 through Day 365

  • Mycophenolate mofetilDrug

    Also called MMF, CellCept

    Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)

Study groups in NCT02833805
Study groupRoleWhat they receive
Bone marrow transplantExperimentalNon-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis.
Receives: Drug: Thymoglobulin; Drug: Fludarabine; Drug: Cyclophosphamide; Radiation: Total body irradiation; Drug: Tacrolimus; Drug: Mycophenolate mofetil

What is being measured

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

  1. Overall Survival and Engraftment at One Year

    Number of enrolled participants who receive BMT, achieve engraftment, and are alive at one year post bone marrow transplant (BMT).

    Measured: 1 year

Secondary outcomes (11)

  1. Overall Survival at One Year

    Number of participants alive at one year after BMT.

    Measured: 1 year

  2. Probability of Neutrophil Recovery as Assessed by the Number of Participants Who Have Recovered Neutrophil Counts

    Probability of neutrophil recovery will be assessed by the number of participants who have recovered neutrophil counts at 1 year (>500 ANC).

    Measured: 1 year

  3. Probability of Platelet Recovery as Assessed by Number of Participants Who Have Recovered Platelet Counts

    Probability of platelet recovery will be assessed by the number of participants who have recovered platelet counts at 1 year.

    Measured: 1 year

  4. Number of Participants Who Experience Primary Graft Failure

    Number of participants who experience primary graft failure by one year after BMT.

    Measured: 1 year

  5. Number of Participants Who Experience Secondary Graft Failure

    Number of participants who experience secondary graft failure by one year after BMT.

    Measured: 1 year

  6. Number of Participants Who Experience Grades II-IV Acute GVHD

    Number of participants who experience grade II, III, or IV acute GVHD by Day 100.

    Measured: Day 100

  7. Number of Participants Who Experience Grades III-IV Acute GVHD

    Number of participants who experience grade III or IV acute GVHD by Day 100.

    Measured: Day 100

  8. Number of Participants Who Experience Chronic GVHD

    Number of participants who experience chronic GVHD by two years after BMT.

    Measured: 2 years

  9. Number of Participants With Full Donor Chimerism

    Number of participants with full donor chimerism at Day 60.

    Measured: Day 60

  10. GVHD-free Relapse-free Survival (GRFS)

    Number of participants alive, without relapse, and without GVHD at 1 year.

    Measured: 1 year

  11. Transplant-related Mortality

    Number of participants deceased for reasons related to BMT at 1 year.

    Measured: 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 posted14 Jul 2016 (estimated)
  2. Study startSep 2016
  3. Primary completionJul 2021
  4. Study completionJul 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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02833805
Sponsor's protocol ID
J1688
Other IDs
IRB00107139
Status last verified
Jun 2022
First submitted
12 Jul 2016
Last updated
12 Jul 2022
Data monitoring committee
No
Individual data sharing
No

Publications

  • DeZern AE, Zahurak M, Symons HJ, Cooke KR, Huff CA, Jain T, Swinnen LJ, Imus PH, Wagner-Johnston ND, Ambinder RF, Levis M, Luznik L, Bolanos-Meade J, Fuchs EJ, Jones RJ, Brodsky RA. Alternative donor BMT with posttransplant cyclophosphamide as initial therapy for acquired severe aplastic anemia. Blood. 2023 Jun 22;141(25):3031-3038. doi: 10.1182/blood.2023020435.

    PubMed 37084383

  • DeZern AE, Zahurak ML, Symons HJ, Cooke KR, Rosner GL, Gladstone DE, Huff CA, Swinnen LJ, Imus P, Borrello I, Wagner-Johnston N, Ambinder RF, Luznik L, Bolanos-Meade J, Fuchs EJ, Jones RJ, Brodsky RA. Haploidentical BMT for severe aplastic anemia with intensive GVHD prophylaxis including posttransplant cyclophosphamide. Blood Adv. 2020 Apr 28;4(8):1770-1779. doi: 10.1182/bloodadvances.2020001729.

    PubMed 32343796

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Thymoglobulin, Fludarabine and Cyclophosphamide in people with Severe Aplastic Anemia and Aplastic Anemia, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins 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 11 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 12 Jul 2022. 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 12 Jul 2022). 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?

Overall Survival and Engraftment at One Year (time frame: 1 year). 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 NCT02833805, which also lists 2 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 12 Jul 2022.

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