Severe Aplastic AnemiaPhase 2NCT02224872
Transplantation of Partially Mismatched Related or Matched Unrelated Bone Marrow for Patients With Refractory Severe Aplastic Anemia
A Phase 2 study testing Bone marrow transplant, Thymoglobulin and Fludarabine in people with Severe Aplastic Anemia and Bone Marrow Failure Syndromes, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 2 sites in United States.
Trial summary
Our primary objective is to determine if it is feasible for SAA patients to be transplanted using non-myeloablative conditioning and post transplantation cyclophosphamide with partially HLA-mismatched donors. Read more about this study
- Who is it for?
- Ages Up to 73 years
- Conditions the study is for
- Severe Aplastic Anemia, Bone Marrow Failure Syndromes
- What is being tested?
- Bone marrow transplant, Thymoglobulin and Fludarabine
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 2 sitesUnited States
- Study dates
- Aug 2014to Dec 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 Up to 73 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with relapsed or refractory SAA or very SAA defined:
- Bone marrow (< 25% cellular)
- Peripheral cytopenias (at least 2 of 3)
- ANC < 500 per ml
- Platelets < 20,000 per ml
- Absolute retic < 60,000 or corrected retic < 1%
Show all 17Show fewer
- Very severe: as above, but ANC < 200
- Disease may be designated as acquired or inherited if previous counts known (these other bone marrow failure disorders that are characterized by aplastic anemia may go by additional names such as dyskeratosis congenita or PNH)
- Failed at least one course of immunosuppressive therapy (if presumed acquired disease). Patients with inherited disease will be characterized as refractory and do not require immunosuppressive first.
- Age 0- upper age limit as determined by current institutional standards
- Good performance status (ECOG 0 or 1; Karnofsky and Lansky 70-100)
- Patients and donors must be able to sign consent forms (or if a minor the parent will sign). Donors should be willing to donate.
- Patients must be geographically accessible and willing to participate in all stages of treatment.
- Adequate end-organ function as measured by:
- Left ventricular ejection fraction > or = to 35%, or shortening fraction > 25% (For pediatric patients, a normal ejection fraction is required)
- Bilirubin ≤ 3.0 mg/dL (unless due to Gilbert's syndrome or hemolysis), and ALT and AST ≤ 5 x ULN
- FEV1 and FVC > or = to 40% of predicted; or in pediatric patients, if unable to perform pulmonary function tests due to young age, oxygen saturation >92% on room air
Who cannot join
- Patients will not be excluded on the basis of sex, racial or ethnic background.
- Prior transfusions from selected donor (as this could have cause recipient alloimmunization against the donor)
- Women of childbearing potential who currently are pregnant (HCG+) or who are not practicing adequate contraception.
- Patients who have any debilitating medical or psychiatric illness that would preclude their giving informed consent or their receiving optimal treatment and follow up.
- Uncontrolled viral, bacterial, or fungal infections (HIV infection permitted if viral load undetectable)
Trial locations and contacts
2 sites in 1 country.
United States2 sites
The Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21287
Medical College of Wisconsin/Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
About this study
Official title: A Phase II Trial of Non-Myeloablative Conditioning and Transplantation of Partially HLA-Mismatched/Haploidentical Related or Matched Unrelated Bone Marrow for Patients With Refractory Severe Aplastic Anemia and Other Bone Marrow Failure Syndromes
Our primary objective is to determine if it is feasible for SAA patients to be transplanted using non-myeloablative conditioning and post transplantation cyclophosphamide with partially HLA-mismatched donors.
Read the detailed description
This research is being done to find out if bone marrow transplantation (BMT) followed by chemotherapy will help people with aplastic anemia who have failed other treatments.
You have a severe, life threatening disease (severe aplastic anemia) in your bone marrow. Your disease has come back or not responded after receiving one or more immunosuppressive treatments. High dose chemotherapy followed by bone marrow transplantation (BMT) has been used to treat blood diseases like yours but complications from Graft vs. Host disease (GVHD) and graft failure have limited the survival for those people.
A small study done at Johns Hopkins has shown that in subjects with other diseases (blood cancers) some immunosuppressive drugs given after the BMT have decreased how often subjects had complications of GVHD and engraftment failure.
People with aplastic anemia who have refractory disease (not responding to standard treatment) may join.
- Being tested
- Bone marrow transplant, Thymoglobulin, Fludarabine, Cyclophosphamide, TBI
- Keywords
- bone marrow transplant, thymoglobulin, cyclophosphamide, fludarabine, tacrolimus, Mycophenolic Acid Mofetil, chemotherapy, GVHD, haploidentical
- 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.
Bone marrow transplantProcedure or surgery
Day 0
ThymoglobulinDrug
0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7
FludarabineDrug
30 mg/M2 IV on days -6 to -2
CyclophosphamideDrug
Also called CTX
14.5 mg/kg IV on days -6, -5, 3, 4
TBIRadiation
200 cGy on day -1
MesnaDrug
40 mg/kg IV on days 3, 4
TacrolimusDrug
For patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present
Mycophenolic acid mofetilDrug
Also called MMF
15 mg/kg PO/IV TID beginning on day 5 through day 35
| Study group | Role | What they receive |
|---|---|---|
| Bone marrow transplant | Experimental | Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35 Receives: Procedure: Bone marrow transplant; Drug: Thymoglobulin; Drug: Fludarabine; Drug: Cyclophosphamide; Radiation: TBI; Drug: Mesna; Drug: Tacrolimus; Drug: Mycophenolic acid mofetil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Is This Type of Transplantation for Severe Aplastic Anemia Feasible and Safe?
Feasibility will be met with the following conditions: the patient has the transplant, is assessed for the safety endpoint, and survives one year. The safety monitoring plan is included to monitor graft failure (day 60), grade 2-4 acute graft versus host disease (day100), 6 month mortality (day 180), and chronic graft versus host disease (day 180).
Measured: 1 year
Secondary outcomes (10)
Number of Patients That Have Survived at One Year
Measured: 1 year
Number of Patients That Have Acheived Full Donor Chimerism by Day 60 After Transplant
Donor chimerism will be measured in the peripheral blood around day 30 and day 60. Patients with >5% donor chimerism around day 60 will be considered as having engrafted.
Measured: 60 days
Number of Patients That Expired Due to Non-relapsed-related Mortality Following Transplant
Measured: 1 year
Number of Participants With Major Toxicities Related to Transplant
Measured: 1 year
Number of Patients That Expired Due to Transplant Related Mortality
Measured: 1 year
Number of Patients With Primary or Secondary Graft Failure Following Transplant
Graft failure: < 5% donor chimerism in blood and/or bone marrow on ~Day 30 or after and on all subsequent measurements.
Primary graft failure: < 5% donor chimerism in blood and/or bone marrow by ~ Day 56 Secondary graft failure: achievement of > 5% donor chimerism, followed by sustained <5% donor chimerism in blood and/or bone marrow.
Measured: 1 year
Number of Participants With Grade II-IV or Grade III-IV Acute GVHD
Participants were graded during clinical visits based on evidence and extent of skin rash, liver involvement, and GI tract involvement
Measured: 1 year
Participants With Chronic GVHD at One Year
Measured: 1 year
Length of Time Required for Patients to Recover ANC and Platelet Counts After Transplant
CBC drawn daily with a WBC differential once the total WBC is greater than 100 until ANC > 500 for three days or two consecutive measurements over a three day period; then CBC drawn weekly with differential.
Measured: 1 year
Participants That Were GVHD Free, Relapse Free Survival (GRFS)
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2014 (estimated)
- Study startAug 2014
- Primary completionDec 2021
- Study completionDec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Severe Aplastic AnemiaStudies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 18 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Amy DeZern, MD, Principal investigator, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02224872
- Sponsor's protocol ID
- J1424
- Other IDs
- IRB00031590
- Status last verified
- Mar 2023
- First submitted
- 18 Aug 2014
- Last updated
- 10 Mar 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Non-Myeloablative Conditioning and Transplantation of Partially HLA-Mismatched/Haploidentical Related or Matched Unrelated Bone Marrow for Patients With Refractory Severe Aplastic Anemia and Other Bone Marrow Failure Syndromes
- ClinicalTrials.gov ID
- NCT02224872
- Acronym / sponsor ID
- J1424
- Keywords
- bone marrow transplant, thymoglobulin, cyclophosphamide, fludarabine, tacrolimus, Mycophenolic Acid Mofetil, chemotherapy, GVHD
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Study start
- Aug 2014
- Primary completion
- Dec 2021 (actual)
- Study completion
- Dec 2021 (actual)
- First posted
- 25 Aug 2014 (estimated)
- Results
- Posted 10 Mar 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Our primary objective is to determine if it is feasible for SAA patients to be transplanted using non-myeloablative conditioning and post transplantation cyclophosphamide with partially HLA-mismatched donors.
Detailed description
This research is being done to find out if bone marrow transplantation (BMT) followed by chemotherapy will help people with aplastic anemia who have failed other treatments.
You have a severe, life threatening disease (severe aplastic anemia) in your bone marrow. Your disease has come back or not responded after receiving one or more immunosuppressive treatments. High dose chemotherapy followed by bone marrow transplantation (BMT) has been used to treat blood diseases like yours but complications from Graft vs. Host disease (GVHD) and graft failure have limited the survival for those people.
A small study done at Johns Hopkins has shown that in subjects with other diseases (blood cancers) some immunosuppressive drugs given after the BMT have decreased how often subjects had complications of GVHD and engraftment failure.
People with aplastic anemia who have refractory disease (not responding to standard treatment) may join.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bone marrow transplant | Experimental | Procedure: Bone marrow transplant, Drug: Thymoglobulin, Drug: Fludarabine, Drug: Cyclophosphamide, Radiation: TBI, Drug: Mesna, Drug: Tacrolimus, Drug: Mycophenolic acid mofetilThymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35 |
Who may qualify
- Ages
- Up to 73 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (17 listed)
- Patients with relapsed or refractory SAA or very SAA defined:
- Age 0- upper age limit as determined by current institutional standards
- Good performance status (ECOG 0 or 1; Karnofsky and Lansky 70-100)
- Patients and donors must be able to sign consent forms (or if a minor the parent will sign). Donors should be willing to donate.
- Patients must be geographically accessible and willing to participate in all stages of treatment.
Key exclusion criteria (5 listed)
- Patients will not be excluded on the basis of sex, racial or ethnic background.
- Prior transfusions from selected donor (as this could have cause recipient alloimmunization against the donor)
- Women of childbearing potential who currently are pregnant (HCG+) or who are not practicing adequate contraception.
- Patients who have any debilitating medical or psychiatric illness that would preclude their giving informed consent or their receiving optimal treatment and follow up.
- Uncontrolled viral, bacterial, or fungal infections (HIV infection permitted if viral load undetectable)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bone marrow transplantDay 0 | Procedure or surgery | Bone marrow transplant |
| Thymoglobulin0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7 | Drug | Bone marrow transplant |
| Fludarabine30 mg/M2 IV on days -6 to -2 | Drug | Bone marrow transplant |
| CyclophosphamideAlso: CTX14.5 mg/kg IV on days -6, -5, 3, 4 | Drug | Bone marrow transplant |
| TBI200 cGy on day -1 | Radiation | Bone marrow transplant |
| Mesna40 mg/kg IV on days 3, 4 | Drug | Bone marrow transplant |
| TacrolimusFor patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present | Drug | Bone marrow transplant |
| Mycophenolic acid mofetilAlso: MMF15 mg/kg PO/IV TID beginning on day 5 through day 35 | Drug | Bone marrow transplant |
Primary outcome
Is This Type of Transplantation for Severe Aplastic Anemia Feasible and Safe?
Time frame: 1 year
Feasibility will be met with the following conditions: the patient has the transplant, is assessed for the safety endpoint, and survives one year. The safety monitoring plan is included to monitor graft failure (day 60), grade 2-4 acute graft versus host disease (day100), 6 month mortality (day 180), and chronic graft versus host disease (day 180).
10 secondary outcomes
Number of Patients That Have Survived at One Year
Time frame: 1 year
Number of Patients That Have Acheived Full Donor Chimerism by Day 60 After Transplant
Time frame: 60 days
Number of Patients That Expired Due to Non-relapsed-related Mortality Following Transplant
Time frame: 1 year
Number of Participants With Major Toxicities Related to Transplant
Time frame: 1 year
Number of Patients That Expired Due to Transplant Related Mortality
Time frame: 1 year
Number of Patients With Primary or Secondary Graft Failure Following Transplant
Time frame: 1 year
Number of Participants With Grade II-IV or Grade III-IV Acute GVHD
Time frame: 1 year
Participants With Chronic GVHD at One Year
Time frame: 1 year
Length of Time Required for Patients to Recover ANC and Platelet Counts After Transplant
Time frame: 1 year
Participants That Were GVHD Free, Relapse Free Survival (GRFS)
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32343796DeZern 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amy DeZern, MD principal investigator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bone marrow transplant, Thymoglobulin and Fludarabine in people with Severe Aplastic Anemia and Bone Marrow Failure Syndromes, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 2 sites 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 17 inclusion and 5 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 10 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 10 Mar 2023). 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?
Is This Type of Transplantation for Severe Aplastic Anemia Feasible and Safe? (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 NCT02224872, which also lists 1 linked publication.
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 10 Mar 2023.