TBI Dose De-escalation for Fanconi Anemia
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ClinicalTrials.gov Identifier: NCT00352976 |
Recruitment Status :
Completed
First Posted : July 17, 2006
Results First Posted : November 24, 2021
Last Update Posted : November 24, 2021
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Condition or disease | Intervention/treatment | Phase |
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Fanconi Anemia | Drug: Cyclophosphamide Drug: Fludarabine Procedure: Total Body Irradiation Procedure: Bone Marrow Transplantation Drug: Mycophenolate Mofetil Drug: Sirolimus | Phase 2 Phase 3 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 83 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Total Body Irradiation Dose De-escalation Study in Patients With Fanconi Anemia Undergoing Alternate Donor Hematopoietic Cell Transplantation |
Actual Study Start Date : | May 18, 2006 |
Actual Primary Completion Date : | October 9, 2020 |
Actual Study Completion Date : | October 9, 2020 |

Arm | Intervention/treatment |
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Experimental: Treatment with TBI
Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
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Drug: Cyclophosphamide
Day -5 through Day -2, subjects will receive chemotherapy of Cyclophosphamide via central line (i.e. Hickman or Broviac),10 mg/kg intravenously (IV)
Other Name: cytoxan Drug: Fludarabine 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)
Other Name: fludara Procedure: Total Body Irradiation 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.
Other Name: Radiation Therapy, Therapeutic radiation Procedure: Bone Marrow Transplantation 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.
Other Name: Stem Cell transplantation Drug: Mycophenolate Mofetil 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).
Other Name: MMF Drug: Sirolimus 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.
Other Name: Rapamycin |
- Number of Participant With Neutrophil Recovery [ Time Frame: by day 42 ]Number of participant with neutrophil recovery. Neutrophil recovery is defined as absolute neutrophil count ≥500/µL for three consecutive days
- Number of Participants Experiencing Grade ≥3 Regimen Related Toxicity [ Time Frame: by day 100 ]Regimen related toxicities (RRT) include: significant hemorrhagic cystitis, pulmonary hemorrhage, interstitial pneumonitis, GI hemorrhage, renal failure, erythroderma, and severe hepatic veno-occlusive disease
- Number of Participants With Secondary Graft Failure at 100 Days [ Time Frame: 100 days ]Secondary Graft Rejection by day 100
- Number of Participants Experiencing Acute Graft-versus-host Disease (GVHD) [ Time Frame: at 100 days ]Number of participants experiencing acute GVHD (all grades) by day 100
- Number of Participants Experiencing Chronic GVHD [ Time Frame: at one year ]Number of participants experiencing chronic Graft Vs Host Disease by 1 year
- Number of Participants Experiencing Overall Survival [ Time Frame: at one year ]Number of participants experiencing overall survival by 1 year
- Number of Participants Experiencing Infections by Day 100 [ Time Frame: by day 100 ]
- Number of Participants Experiencing Infections by Day 180 [ Time Frame: by day 180 ]
- Number of Participants Experiencing Infections by Day 365 [ Time Frame: by day 365 ]
- Average Immunoglobulin G (IgG) Levels as a Measure of Immune Reconstitution After Transplant, by 100 Days [ Time Frame: by 100 days ]
- Average IgG Levels as a Measure of Immune Reconstitution After Transplant, by 180 Days [ Time Frame: by 180 days ]
- Average IgG Levels as a Measure of Immune Reconstitution After Transplant by 365 Days [ Time Frame: by 365 days ]
- Average IgA Levels as a Measure of Immune Reconstitution After Transplant by 100 Days [ Time Frame: by 100 days ]
- Average IgA Levels as a Measure of Immune Reconstitution After Transplant by 180 Days [ Time Frame: by 180 days ]
- Average IgA Levels as a Measure of Immune Reconstitution After Transplant by 365 Days [ Time Frame: by 365 days ]
- Average IgM Levels as a Measure of Immune Reconstitution After Transplant by 100 Days [ Time Frame: by 100 days ]
- Average IgM Levels as a Measure of Immune Reconstitution After Transplant by 180 Days [ Time Frame: by 180 days ]
- Average IgM Levels as a Measure of Immune Reconstitution After Transplant by 365 Days [ Time Frame: by 365 days ]

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | Child, Adult, Older Adult |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Meeting the definition of standard risk or high risk Fanconi anemia as defined in the next two sections:
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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:
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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)
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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)
- Patients must have an appropriate source of stem cells. Patients and donors will be typed for HLA-A, B, C and DRB1 using high resolution molecular typing.
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Adequate major organ function including:
- Cardiac: ejection fraction >45%
- Hepatic: bilirubin, AST or ALT, ALP <5 x normal
- Karnofsky performance status >70% or Lansky >50 (if < 16 years of age)
- Women of child-bearing age must be using adequate birth control and have a negative pregnancy test.
- Written consent.
Exclusion Criteria:
- 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).

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00352976
United States, Minnesota | |
University of Minnesota Medical Center | |
Minneapolis, Minnesota, United States, 55455 |
Principal Investigator: | Margaret L MacMillan, M.D. | University of Minnesota Medical Center |
Documents provided by Masonic Cancer Center, University of Minnesota:
Publications:
Responsible Party: | Masonic Cancer Center, University of Minnesota |
ClinicalTrials.gov Identifier: | NCT00352976 |
Other Study ID Numbers: |
MT2006-05 0605M85788 ( Other Identifier: IRB, University of Minnesota ) |
First Posted: | July 17, 2006 Key Record Dates |
Results First Posted: | November 24, 2021 |
Last Update Posted: | November 24, 2021 |
Last Verified: | October 2021 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Bone Marrow transplant stem cell transplant cord blood transplant total body irradiation thymic shielding |
Fanconi Syndrome Anemia Fanconi Anemia Hematologic Diseases Anemia, Hypoplastic, Congenital Anemia, Aplastic Congenital Bone Marrow Failure Syndromes Bone Marrow Failure Disorders Bone Marrow Diseases Genetic Diseases, Inborn DNA Repair-Deficiency Disorders Metabolic Diseases Renal Tubular Transport, Inborn Errors Kidney Diseases Urologic Diseases |
Mycophenolic Acid Sirolimus Cyclophosphamide Fludarabine Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Antibiotics, Antineoplastic Antibiotics, Antitubercular |