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

NCT03600909 | Terminated Phase 2 Results FDA Drug FDA Device

• 1 other identifier: 17-498
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 3

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 .

Conditions

Fanconi Anemia; Myelodysplastic Syndrome (MDS); Acute Myelogenous Leukemia (AML)

Keywords

Blood Stem Cell Transplant; busulfan; cyclophosphamide; fludarabine; 17-498

Outcome Measures

Primary Outcomes (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.

  5 years

Study Arms (3)

Good Risk Patients

EXPERIMENTAL

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).

Drug: Busulfan; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Anti-Thymocyte Globulin (Rabbit); Device: The CliniMACS device; Drug: G-CSF

Intermediate risk patients

EXPERIMENTAL

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).

Drug: Busulfan; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Anti-Thymocyte Globulin (Rabbit); Device: The CliniMACS device; Drug: G-CSF

High risk patients

EXPERIMENTAL

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).

Drug: Busulfan; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Anti-Thymocyte Globulin (Rabbit); Device: The CliniMACS device; Drug: G-CSF

Interventions

Busulfan DRUG

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.

Also known as: busulfex®

Good Risk Patients; High risk patients; Intermediate risk patients

Fludarabine DRUG

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.

Also known as: FLUDARA®

Good Risk Patients; High risk patients; Intermediate risk patients

Cyclophosphamide DRUG

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.

Also known as: Cytoxan®

Good Risk Patients; High risk patients; Intermediate risk patients

Anti-Thymocyte Globulin (Rabbit) DRUG

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

Also known as: hymoglobulin®

Good Risk Patients; High risk patients; Intermediate risk patients

The CliniMACS device DEVICE

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)

Good Risk Patients; High risk patients; Intermediate risk patients

G-CSF DRUG

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

Also known as: Granulocyte colony-stimulating factor, filgrastim

Good Risk Patients; High risk patients; Intermediate risk patients

Eligibility Criteria

• Age: 1 Month+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• \. 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
• Hgb \<8 gm/dl or red cell transfusion dependence\*
• \. 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Pediatric Brain Tumor Consortium: collaborator

Study Sites (3)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Fanconi Anemia; Myelodysplastic Syndromes; Leukemia, Myeloid, Acute

Interventions

Busulfan; fludarabine; fludarabine phosphate; Cyclophosphamide; Antilymphocyte Serum; Granulocyte Colony-Stimulating Factor; Filgrastim

Condition Hierarchy (Ancestors)

Anemia, Hypoplastic, Congenital; Anemia, Aplastic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders; Bone Marrow Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors

Results Point of Contact

• Title: Dr. Farid Boulad, MD
• Organization: Memorial Sloan Kettering Cancer Center

bouladf@MSKCC.ORG

1-833-MSK-KIDS

Study Officials

• Farid Boulad, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: July 17, 2018
• First Posted: July 26, 2018
• Study Start: May 15, 2018
• Primary Completion: April 9, 2021
• Study Completion: April 9, 2021
• Last Updated: April 12, 2022
• Results First Posted: April 12, 2022

Record last verified: 2021-04

Locations

US (3)