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Fanconi AnemiaPhase 2NCT03600909

A Study of the Effect of Blood Stem Cell Transplant After Chemotherapy Alone in Patients With Fanconi Anemia

A Phase 2 study testing Busulfan, Fludarabine and Cyclophosphamide in people with Fanconi Anemia and Myelodysplastic Syndrome (MDS), run by Memorial Sloan Kettering Cancer Center at 3 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The goal of this study is to see if the study therapy can decrease the chemotherapy-related side effects while maximizing the effectiveness of disease control. The physicians will also be studying the effect of removing T-cells from the donor"s stem cells before transplant. Read more about this study

Who is it for?
Ages 1 month and older
What is being tested?
Busulfan, Fludarabine and Cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
3 sitesUnited States
Study dates
15 May 2018to 9 Apr 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 1 month and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Patients must have a diagnosis of Fanconi anemia (confirmed by mitomycin C or diepoxybutane [DEB] chromosomal breakage testing at a CLIA approved laboratory).
  • Patients must have one of the following hematologic diagnoses:
  • 1. Severe Aplastic Anemia (SAA), with bone marrow cellularity of <25% OR Severe Isolated Single lineage Cytopenia
  • AND at least one of the following features:
  • Platelet count <20 x 10^9/L or platelet transfusion dependence*
  • ANC <1000 x 10^9/L
Show all 30Show fewer
  • Hgb <8 gm/dl or red cell transfusion dependence*
  • 2. Myelodysplastic Syndrome (MDS) (Appendix 1: MDS Classification)
  • MDS at any stage, based on either one of the following classifications:
  • WHO Classification
  • Refractory anemia and transfusion dependence*
  • Any of other stages
  • IPSS Classification
  • Low risk (score 0) and transfusion dependence*
  • Any other risk groups Score > 0.5 Note that patients with chromosome 1q cytogenetic abnormalities in the absence of morphologic dysplasia will not be considered to have MDS.
  • 3. Acute Myelogenous Leukemia Patients with acute leukemia are included in this trial untreated, in remission or with refractory or relapsed disease.
  • Transfusion dependence will be defined as greater than ONE transfusion of platelets or red blood cells in the last year prior to evaluation on protocol.
  • Donor
  • Donor choices will be determined by the investigators according to institutional criteria. Patients who will be enrolled on this protocol must have one of the following donor choices:
  • HLA-compatible unrelated volunteer donors Patients who do not have a related HLA-matched donor but have an unrelated donor who is either matched at all A, B, C and DRB1 (8/8) loci or who is mismatched at no more than 2/8 loci (A, B, C or DRB1) (6/8) as tested by DNA analysis (high resolution), will be eligible for entry on this protocol.
  • HLA-mismatched Related donors Patients who do not have a related or unrelated HLA-compatible donor must have a healthy family member who is at least HLA-haplotype identical to the recipient. First degree related donors must have a normal DEB test.
  • The donor must be healthy and willing and able to receive a 4-6 day course of G-CSF and undergo 1-3 daily leukaphereses, as per institutional guidelines.
  • Related and unrelated donors must be medically evaluated and fulfill the criteria for collection of PBSCs as per institutional guidelines.
  • Patients and donors may be of either gender or any ethnic background. Patients must have a Karnofsky adult, or Lansky pediatric performance scale status ≥ 70%.
  • Patients must have adequate physical function measured by :
  • Cardiac: asymptomatic or if symptomatic then 1) LVEF at rest must be ≥ 50% and must improve with exercise or 2) Shortening Fraction ≥ 29%
  • Hepatic: < 5 x ULN alanine transaminase (ALT) and < 2.0 mg/dl total serum bilirubin.
  • Renal: serum creatinine ≤1.5 mg/dl or if serum creatinine is outside the normal range, then CrCl > 50 ml/min/1.73 m^2
  • Pulmonary: asymptomatic or if symptomatic, DLCO > 50% of predicted (corrected for hemoglobin) Each patient must be willing to participate as a research subject and must sign an informed consent form. Parent or legal guardians of patients who are minors will sign the informed consent form. Assents will be obtained as per institutional guidelines.
  • Female patients and donors must not be pregnant or breastfeeding at the time of signing consent. Women must be willing to undergo a pregnancy test prior to transplant and avoid becoming pregnant while on study. Positive pregnancy test results will be reported to the parent(s) or guardian of minor participants, as required per institutional guidelines.

Who cannot join

  • Active CNS leukemia Female patients who are pregnant (positive serum or urine HCG) or breast-feeding. Women of childbearing age must avoid becoming pregnant while on study.
  • Active uncontrolled viral, bacterial or fungal infection Patient seropositive for HIV-I/II; HTLV -I/II

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Fred Hutchinson Cancer Research Center

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: A Phase II Trial of Hematopoietic Stem Cell Transplantation for the Treatment of Patients With Fanconi Anemia Lacking a Genotypically Identical Donor, Using a Risk-Adjusted Chemotherapy Only Cytoreduction With Busulfan, Cyclophosphamide and Fludarabine

The goal of this study is to see if the study therapy can decrease the chemotherapy-related side effects while maximizing the effectiveness of disease control. The physicians will also be studying the effect of removing T-cells from the donor"s stem cells before transplant. T-cells are a type of white blood cell that may help cause a serious side effect of transplant called Graft versus Host Disease (GVHD). The way it removes the T-cells from the donor stem cells is actually by selecting only the stem cells (called CD34 cells) by using a device called CliniMACS. This process is called CD34 selection. The CliniMACS® device is currently under the supervision of the FDA .

Being tested
Busulfan, Fludarabine, Cyclophosphamide, Anti-Thymocyte Globulin (Rabbit), The CliniMACS device
Keywords
Blood Stem Cell Transplant, busulfan, cyclophosphamide, fludarabine, 17-498
Medical subject headings
Fanconi Anemia, Myelodysplastic Syndromes, Leukemia, Myeloid, Acute

What participants receive

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

  • BusulfanDrug

    Also called busulfex®

    A standard dose of busulfan, associated with excellent outcomes in our previous trial will be used for young patients with marrow aplasia (arm A).

    A higher dose of busulfan will be used in younger patients with MDS and AML (arm B) to maximize disease control.

    A lower dose of busulfan will be used in older patients (arm C) to minimize toxicity.

  • FludarabineDrug

    Also called FLUDARA®

    Arms A, B and C - Fludarabine will be given IV over 30 minutes daily for 4 days. The dose will be adjusted according to renal function according to Institutional guidelines.

  • CyclophosphamideDrug

    Also called Cytoxan®

    Arms A, B and C - Cytoxan will be given as a 1-2 hour infusion for 4 days. The dose will be adjusted according to patients ideal body weight for obese patients.

  • Anti-Thymocyte Globulin (Rabbit)Drug

    Also called hymoglobulin®

    Arms A, B and C - 4 doses will be given prior to transplant to promote engraftment

  • The CliniMACS deviceDevice

    The source of stem cells for all patients will be peripheral blood stem cells (PBSC) induced and mobilized by treatment of the donor with G-CSF for 4-6 days. T-cell depletion will be uniformly performed by positive CD34 selection with the use of the Miltenyi system (CliniMACS device)

  • G-CSFDrug

    Also called Granulocyte colony-stimulating factor, filgrastim

    All patients will also receive G-CSF post-transplant to foster engraftment.

Study groups in NCT03600909
Study groupRoleWhat they receive
Good Risk PatientsExperimentalPatients 18 years old or younger with marrow aplasia or single lineage cytopenias (Arm A) will be conditioned for transplantation with intravenous busulfan (busulfex®) (0.6-0.8 mg/Kg/dose q 12 hours x 4 doses), cyclophosphamide (10 mg/Kg/dose x 4 doses) and fludarabine (35mg/m2/day x 4 doses).
Receives: Drug: Busulfan; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Anti-Thymocyte Globulin (Rabbit); Device: The CliniMACS device; Drug: G-CSF
Intermediate risk patientsExperimentalPatients 18 years old or younger with MDS or AML will be will be conditioned for transplantation with intravenous busulfan (busulfex®) (0.8-1.0mg/Kg/dose q 12 hours x 4 doses), cyclophosphamide (10 mg/Kg/dose x 4 doses) and fludarabine (35mg/m2/day x 4 doses).
Receives: Drug: Busulfan; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Anti-Thymocyte Globulin (Rabbit); Device: The CliniMACS device; Drug: G-CSF
High risk patientsExperimentalPatients 19 years old or older with marrow aplasia or MDS or AML will be will be conditioned for transplantation with intravenous busulfan (busulfex®) (0.4mg/Kg/dose q 12 hours x 4 doses), cyclophosphamide (10 mg/Kg/dose x 4 doses) and fludarabine (35mg/m2/day x 4 doses).
Receives: Drug: Busulfan; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Anti-Thymocyte Globulin (Rabbit); Device: The CliniMACS device; Drug: G-CSF

What is being measured

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

  1. Graft Failure or Rejection

    Primary non-engraftment is diagnosed when the patient fails to achieve an ANC ≥500/µl at any time in the first 28 days post-transplant. If (1) after achievement of an ANC ≥500/mm^3, the ANC declines to <500/mm^3 for more than 3 consecutive days in the absence of relapse, or, (2) there is absence of donor cells in the marrow and/or blood as demonstrated by chimerism assay in the absence of relapse, a diagnosis of secondary graft failure is made. The patient is not evaluable for graft failure or rejection if recurrence of host MDS is detected concurrently.

    Measured: 5 years

Timeline

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

  1. First posted26 Jul 2018
  2. Study start15 May 2018
  3. Primary completion9 Apr 2021
  4. Study completion9 Apr 2021

Why it stopped: Accrual has been slow

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
Non-randomised
Intervention model
Parallel groups
Model description
A three-arm phase II treatment protocol designed to examine engraftment, toxicity, graft-versus-host disease, and disease-free survival following a novel cytoreductive regimen including busulfan, cyclophosphamide and fludarabine and ATG
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03600909
Sponsor's protocol ID
17-498
Status last verified
Apr 2021
First submitted
17 Jul 2018
Last updated
12 Apr 2022
FDA-regulated drug
Yes
FDA-regulated device
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Busulfan, Fludarabine and Cyclophosphamide in people with Fanconi Anemia and Myelodysplastic Syndrome (MDS), run by Memorial Sloan Kettering Cancer Center at 3 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 30 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: stopped early, as of the sponsor's last update on 12 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 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 12 Apr 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?

Graft Failure or Rejection (time frame: 5 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 NCT03600909.

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 Apr 2022.

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