NCT00358657

Fludarabine Phosphate, Cyclophosphamide, and Total-Body Irradiation Followed by Donor Bone Marrow Transplant and Cyclophosphamide, Mycophenolate Mofetil, Tacrolimus, and Sirolimus in Treating Patients With Primary Immunodeficiency Disorders or Noncancerous Inherited Disorders

Terminated Phase 2 Results posted Last updated 26 January 2021

What this trial tests

Phase 2 trial testing Allogeneic Bone Marrow Transplantation in Immunodeficiency Syndrome in 14 participants. Terminated before completion.

Timeline

24 May 2006

Primary endpoint
17 August 2018

25 May 2019

Quick facts

Lead sponsor	Fred Hutchinson Cancer Center
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	14
Start date	24 May 2006
Primary completion	17 August 2018
Estimated completion	25 May 2019
Sites	3 locations across United States

Drugs / interventions tested

• Allogeneic Bone Marrow Transplantation
• Cyclophosphamide
• Fludarabine Phosphate (FLUDARABINE PHOSPHATE) — full drug profile →
• Laboratory Biomarker Analysis
• Mycophenolate Mofetil (MYCOPHENOLATE MOFETIL) — full drug profile →
• Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation
• Sirolimus (sirolimus) — full drug profile →
• Tacrolimus
• Total-Body Irradiation

Conditions studied

• Immunodeficiency Syndrome — all drugs for Immunodeficiency Syndrome →
• Severe Aplastic Anemia — all drugs for Severe Aplastic Anemia →
• Genetic Disorder — all drugs for Genetic Disorder →

Sponsor

Fred Hutchinson Cancer Center — full company profile →

Who can join

Under 55, any sex, with Immunodeficiency Syndrome or Severe Aplastic Anemia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Graft Rejection Primary · Day 84

Number of patients with graft rejection (CD3 donor chimerisms \<5%).

Group	Value	95% CI
Treatment (Chemo, Total-body Irradiation, Transplant)	1

Graft Failure Primary · Day 84

Number of patients with graft failure (grade IV thrombocytopenia and neutropenia after day 21 that lasts \> 2 weeks andn is refractory to growth factor support).

Group	Value	95% CI
Treatment (Chemo, Total-body Irradiation, Transplant)	0

Proportion of Patients Who Achieve Greater Than 5% Donor T-cell Chimerism Secondary · By day 84

Number of patients who achieve greater than 5% donor T-cell (CD3+) chimerisms

Group	Value	95% CI
Treatment (Chemo, Total-body Irradiation, Transplant)	13

Number of Patients With Transplant Related Mortality Secondary · Day 100 post transplant

The number of patients with transplant related mortality

Group	Value	95% CI
Treatment (Chemo, Total-body Irradiation, Transplant)	0

Incidence of Grade I/II Acute Graft Versus Host Disease (GVHD) Secondary · Day 100 post transplant

Number of patients diagnosed with overall GI/G2 acute GVHD by Day 100

Group	Value	95% CI
Treatment (Chemo, Total-body Irradiation, Transplant)	7

Incidence of Grade III/IV Acute Graft Versus Host Disease (GVHD) Secondary · Day 100 post transplant

Number of patients diagnosed with overall GIII/IV acute GVHD by Day 100

Group	Value	95% CI
Treatment (Chemo, Total-body Irradiation, Transplant)	5

Incidence of Chronic GVHD Secondary · 1 year post transplant

Number of patients diagnosed with chronic GVHD by 1 year post transplant

Group	Value	95% CI
Treatment (Chemo, Total-body Irradiation, Transplant)	11

Immune Reconstitution Secondary · 1 year post transplant

Number of patients with normal range CD3 @ 1 year post transplant

Group	Value	95% CI
Treatment (Chemo, Total-body Irradiation, Transplant)	4

Number of Patients With Infections Secondary · Through day 200 after HCT

Number of patients with clinically significant infections requiring treatment within 200 days after HCT

Group	Value	95% CI
Treatment (Chemo, Total-body Irradiation, Transplant)	11

Adverse events — posted to ClinicalTrials.gov

Time frame: Day 200 post initiation of conditioning therapy. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment (Chemo, Total-body Irradiation, Transplant)

Serious: 1/14 (7%)

Deaths: 1/14

Serious adverse events (3 terms)

Reaction	System	Treatment (Chemo, Total-bo…
Hypoxia requiring mechanical ventilation	Respiratory, thoracic and mediastinal disorders	—
Sepsis	Infections and infestations	—
Pancreatitis with shock	Gastrointestinal disorders	—

Other adverse events (11 terms — click to expand)

Reaction	System	Treatment (Chemo, Total-bo…
Febrile neutropenia	Blood and lymphatic system disorders	—
Hypotension	Vascular disorders	—
Pericardial effusion	Cardiac disorders	—
Typhlitis	Gastrointestinal disorders	—
Pancreatisis	Gastrointestinal disorders	—
Mucositis oral	Gastrointestinal disorders	—
Blood bilirubin increased	Investigations	—
Hypoxia	Respiratory, thoracic and mediastinal disorders	—
Seizure	Nervous system disorders	—
Hemolytic uremic syndrome	Blood and lymphatic system disorders	—
Acute kidney injury	Renal and urinary disorders	—

Most-reported serious reactions: Hypoxia requiring mechanical ventilation, Sepsis, Pancreatitis with shock.

Data from ClinicalTrials.gov NCT00358657 adverse events section.

Sponsor's own description

This phase I/II trial studies the side effects of fludarabine phosphate, cyclophosphamide and total-body irradiation followed by donor bone marrow transplant and cyclophosphamide, mycophenolate mofetil, tacrolimus, and sirolimus in treating patients with primary immunodeficiency disorders or noncancerous inherited disorders. Giving low doses of chemotherapy and total-body irradiation before a bone marrow transplant helps prepare the patient's body to accept the incoming donor's bone marrow and decrease the risk that the patient's immune system will reject the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells called graft versus host disease. Giving cyclophosphamide, mycophenolate mofetil, tacrolimus, and sirolimus after the transplant may help decrease this from happening.

Publications & conference data

No peer-reviewed publications indexed yet for this trial.