TBI Dose De-escalation for Fanconi Anemia

NCT00352976 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: MT2006-050605M85788
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single arm, total body irradiation (TBI) trial. All patients will be prescribed TBI 300 cGy with the goal of evaluating secondary endpoints.

Conditions

Fanconi Anemia

Keywords

Bone Marrow transplant; stem cell transplant; cord blood transplant; total body irradiation; thymic shielding

Outcome Measures

Primary Outcomes (1)

• Number of Participant With Neutrophil Recovery

  Number of participant with neutrophil recovery. Neutrophil recovery is defined as absolute neutrophil count ≥500/µL for three consecutive days

  by day 42

Secondary Outcomes (17)

• Number of Participants Experiencing Grade ≥3 Regimen Related Toxicity

  by day 100

• Number of Participants With Secondary Graft Failure at 100 Days

  100 days

• Number of Participants Experiencing Acute Graft-versus-host Disease (GVHD)

  at 100 days

• Number of Participants Experiencing Chronic GVHD

  at one year

• Number of Participants Experiencing Overall Survival

  at one year

Study Arms (1)

Treatment with TBI

EXPERIMENTAL

Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.

Drug: Cyclophosphamide; Drug: Fludarabine; Procedure: Total Body Irradiation; Procedure: Bone Marrow Transplantation; Drug: Mycophenolate Mofetil; Drug: Sirolimus

Interventions

Cyclophosphamide DRUG

Day -5 through Day -2, subjects will receive chemotherapy of Cyclophosphamide via central line (i.e. Hickman or Broviac),10 mg/kg intravenously (IV)

Also known as: cytoxan

Treatment with TBI

Fludarabine DRUG

Day -5 through Day -2 prior to transplant; subjects will receive chemotherapy of Fludarabine via central line (i.e. Hickman or Broviac),35 mg/m\^2 intravenous (IV)

Also known as: fludara

Treatment with TBI

Total Body Irradiation PROCEDURE

total body irradiation (300 cGy) with thymic shielding will be given six days before the stem cells are given (day -6). Thymic shielding is done by placing a piece of lead on the chest during the irradiation treatment so that the irradiation beams do not go to the thymus.

Also known as: Radiation Therapy, Therapeutic radiation

Treatment with TBI

Bone Marrow Transplantation PROCEDURE

A target of 5 \* 10\^6/kg and a minimum of 4 \* 10\^6 CD34+ cell/kg recipient weight will be collected by apheresis and used for transplant. In most cases this dose will be recovered in a single apheresis; however, a second or rarely third apheresis performed on the following days may be required to achieve the minimum dose.

Also known as: Stem Cell transplantation

Treatment with TBI

Mycophenolate Mofetil DRUG

Patients will receive MMF therapy beginning on day -3 through day +30 or for 7 days after engraftment, whichever day is later, if no acute graft-versus-host disease (GVHD). Engraftment is defined as 1st day of 3 consecutive days of absolute neutrophil count \[ANC\] \> 0.5 \* 10\^9/L. MMF will be given at a dose of 15 mg/kg/dose every 8 hours by mouth(to a maximum dose of 1 gram).

Also known as: MMF

Treatment with TBI

Sirolimus DRUG

Sirolimus will be administered starting at day -3 with 8mg-12mg mg oral loading dose followed by single dose 4 mg/day with a target serum concentration of 3 to 12 mg/mL by high-performance liquid chromatography (HPLC). Levels are to be monitored 3 times/week in the first 2 weeks, weekly until day +60, and as clinically indicated until day +100 post-transplantation. In the absence of acute GVHD sirolimus may be tapered starting at day +100 and eliminated by day +180 post-transplantation.

Also known as: Rapamycin

Treatment with TBI

Eligibility Criteria

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

You may qualify if:

• Meeting the definition of standard risk or high risk Fanconi anemia as defined in the next two sections:
• Standard risk patients must be \<18 years of age with a diagnosis of Fanconi anemia with aplastic anemia (AA), myelodysplastic syndrome without excess blasts, or high risk genotype as defined below:
• Aplastic anemia is defined as having at least one of the following when not receiving growth factors or transfusions:
• platelet count \<20 \* 10\^9/L
• ANC \<5 \* 10\^8/L
• Hemoglobin \<8 g/dL
• Myelodysplastic syndrome (MDS) with multilineage dysplasia with or without chromosomal anomalies
• High risk genotype (e.g. IVS-4 or exon 14 FANCC mutations, or BRCA1 or 2 mutations)
• High risk patients must have one or more of the following high risk features:
• Advanced MDS (≥ 5% blast) or acute leukemia
• Require additional HSCT for graft failure
• History at any time of systemic fungal or gram negative infection
• Severe renal disease with a creatinine clearance \<40 mL/min
• Age \> 18 years
• Very high risk patients must have Advanced MDS (≥ 5% blast) or acute leukemia after initial hematopoietic stem cell transplant (HSCT)

You may not qualify if:

• Available HLA-genotypically identical related donor in standard risk patients.
• Active central nervous system (CNS) leukemia at time of study enrollment.
• History of squamous cell carcinoma of the head/neck/cervix within previous 2 years.
• Prior radiation therapy that prevents further total body irradiation (TBI).

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

University of Minnesota Medical Center

Minneapolis, Minnesota, 55455, United States

Location

Related Publications (1)

• MacMillan ML, DeFor TE, Young JA, Dusenbery KE, Blazar BR, Slungaard A, Zierhut H, Weisdorf DJ, Wagner JE. Alternative donor hematopoietic cell transplantation for Fanconi anemia. Blood. 2015 Jun 11;125(24):3798-804. doi: 10.1182/blood-2015-02-626002. Epub 2015 Mar 30.

  PMID: 25824692 BACKGROUND

Related Links

• Trial 4 listed in the article corresponds to this clinical trial.

MeSH Terms

Conditions

Fanconi Anemia

Interventions

Cyclophosphamide; fludarabine; fludarabine phosphate; Whole-Body Irradiation; Radiotherapy; Bone Marrow Transplantation; Stem Cell Transplantation; Mycophenolic Acid; Sirolimus

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Therapeutics; Investigative Techniques; Tissue Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative; Cell Transplantation; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Macrolides; Lactones

Results Point of Contact

• Title: Margaret L. MacMillan, M.D.
• Organization: Masonic Cancer Center, University of Minnesota

macmi002@umn.edu

612-626-2961

Study Officials

• Margaret L MacMillan, M.D.

  University of Minnesota Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2006
• First Posted: July 17, 2006
• Study Start: May 18, 2006
• Primary Completion: October 9, 2020
• Study Completion: October 9, 2020
• Last Updated: November 24, 2021
• Results First Posted: November 24, 2021

Record last verified: 2021-10

Locations

US (1)