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
A Study of the Effect of Blood Stem Cell Transplant After Chemotherapy Alone in Patients With Fanconi Anemia
Sponsors
Source
Memorial Sloan Kettering Cancer Center
Oversight Info
Is Fda Regulated Drug
Yes
Is Fda Regulated Device
Yes
Is Unapproved Device
No
Brief 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.
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 .
Overall Status
Recruiting
Start Date
2018-05-15
Completion Date
2022-05-01
Primary Completion Date
2022-05-01
Phase
Phase 2
Study Type
Interventional
Primary Outcome
Measure |
Time Frame |
Graft Failure or Rejection |
5 years |
Enrollment
70
Conditions
Intervention
Intervention Type
Drug
Intervention Name
Description
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.
Arm Group Label
Good Risk Patients
Intermediate risk patients
High risk patients
Other Name
busulfex®
Intervention Type
Drug
Intervention Name
Description
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.
Arm Group Label
Good Risk Patients
Intermediate risk patients
High risk patients
Other Name
FLUDARA®
Intervention Type
Drug
Intervention Name
Description
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.
Arm Group Label
Good Risk Patients
Intermediate risk patients
High risk patients
Other Name
Cytoxan®
Intervention Type
Drug
Intervention Name
Description
Arms A, B and C - 4 doses will be given prior to transplant to promote engraftment
Arm Group Label
Good Risk Patients
Intermediate risk patients
High risk patients
Other Name
hymoglobulin®
Intervention Type
Device
Intervention Name
Description
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)
Arm Group Label
Good Risk Patients
Intermediate risk patients
High risk patients
Intervention Type
Drug
Intervention Name
Description
All patients will also receive G-CSF post-transplant to foster engraftment.
Arm Group Label
Good Risk Patients
Intermediate risk patients
High risk patients
Other Name
Granulocyte colony-stimulating factor, filgrastim
Eligibility
Criteria
Inclusion Criteria:
- 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:
1. Platelet count <20 x 10^9/L or platelet transfusion dependence*
2. ANC <1000 x 10^9/L
3. 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 :
1. Cardiac: asymptomatic or if symptomatic then 1) LVEF at rest must be ≥ 50% and must
improve with exercise or 2) Shortening Fraction ≥ 29%
2. Hepatic: < 5 x ULN alanine transaminase (ALT) and < 2.0 mg/dl total serum bilirubin.
3. 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
4. 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.
Exclusion Criteria:
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
Gender
All
Minimum Age
1 Month
Maximum Age
N/A
Healthy Volunteers
No
Overall Official
Last Name |
Role |
Affiliation |
Farid Boulad, MD |
Principal Investigator |
Memorial Sloan Kettering Cancer Center |
Overall Contact
Location
Facility |
Status |
Contact |
Investigator |
Memorial Sloan Kettering Cancer Center New York New York 10065 United States |
Recruiting |
Last Name: Farid Boulad, MD Phone: 212-639-6684 |
Last Name: Faird Boulad, MD Role: Principal Investigator |
Location Countries
Country
United States
Verification Date
2019-10-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Responsible Party Type
Sponsor
Keywords
Condition Browse
Number Of Arms
3
Intervention Browse
Mesh Term
Vidarabine
Cyclophosphamide
Busulfan
Fludarabine
Fludarabine phosphate
Antilymphocyte Serum
Thymoglobulin
Arm Group
Arm Group Label
Good Risk Patients
Arm Group Type
Experimental
Description
Patients 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).
Arm Group Label
Intermediate risk patients
Arm Group Type
Experimental
Description
Patients 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).
Arm Group Label
High risk patients
Arm Group Type
Experimental
Description
Patients 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).
Firstreceived Results Date
N/A
Overall Contact Backup
Last Name
Maria Cancio, MD
Phone
212-639-2446
Firstreceived Results Disposition Date
N/A
Study Design Info
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Intervention 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
Primary Purpose
Treatment
Masking
None (Open Label)
Study First Submitted
July 17, 2018
Study First Submitted Qc
July 17, 2018
Study First Posted
July 26, 2018
Last Update Submitted
October 4, 2019
Last Update Submitted Qc
October 4, 2019
Last Update Posted
October 7, 2019
ClinicalTrials.gov processed this data on December 06, 2019
Conditions
Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov,
conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.