Bone Marrow Stromal Cell Infusions for Stem Cell Transplant Complications

NCT01633229 | Completed Phase 1

• 2 other identifiers: 12001012-H-0010
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Background:

• Bone marrow stromal cells (BMSC) from bone marrow biopsies can be used to treat disorders that cause inflammation and immune system diseases. BMSC have been used to treat graft versus host disease (GVHD), a complication that can develop after stem cell transplants. BMSC have also been used to treat other post-transplant complications, like marrow failure or tissue injury.
• The National Institutes of Health (NIH) has developed a procedure for collecting and preserving BMSC from volunteer donors. These donors have passed tests to ensure that their cells are healthy enough to be used for treatment. Researchers want to use the collected cells to treat people with GVHD, marrow failure, or tissue injury following stem cell transplants. Objectives: \- To test the safety and effectiveness of NIH-collected BMSC to treat complications from stem cell transplants. Eligibility:
• Individuals between 18 and 75 years of age who have complications from stem cell transplants.
• Complications are acute GVHD, poor bone marrow function, or tissue or organ damage. Design:
• Participants will be screened with a physical exam and medical history. They will also have imaging studies and blood tests.
• Participants will provide blood, skin, and bone marrow samples before the BMSC treatment. Additional samples, including tissue samples, will be collected after the start of treatment.
• Participants will have up to three BMSC infusions. There will be a week between each infusion. Participants will be monitored closely during each infusion. Any side effects will be treated.
• Treatment will be monitored with frequent blood tests and physical exams.
• After the end of the infusions, participants will have regular followup visits for up to 2 years.

Conditions

Graft-Versus-Host Disease

Keywords

Immune Suppression; BMSC; GVHD; Marrow Failure; Regimen Related Toxicity; Graft-Versus-Host Disease

Outcome Measures

Primary Outcomes (1)

• The primary endpoint to this study is to characterize the safety of bone marrow stromal cells (BMSC).

Interventions

Bone Marrow Stromal Cell Infusion PROCEDURE

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• History of allogeneic SCT
• Any subject who has received an allogeneic SCT at NIH is eligible if they have one or more of the following conditions. Subjects may continue to receive standard treatments for their condition but may not be entered onto a new investigational protocol to treat the condition during the period of evaluation of BMSC infusions.
• Acute GVHD
• Biopsy confirmed within 14 days of investigational intervention (unless not possible to perform because of anatomical location or clinical contraindication) acute GVHD affecting gut and/or liver and/or skin, defined as steroid refractory: failure to respond to greater than or equal to 2mg/kg methylprednisolone (or equivalent) after 7 days OR steroid dependent: requiring methylprednisolone (or equivalent) greater than or equal to 1mg/kg for greater than or equal to 7days for control of GVHD. GVHD affecting the skin alone is rarely lethal and is excluded. Acute GVHD is defined using the NIH consensus definition inclusive of Classic acute (\< 100 days after transplant or DLI, presence of acute GVHD features, absence of chronic GVHD features) AND Persistent/recurrent/late onset acute (\> 100 days after transplant or DLI, presence of acute GVHD features, absence of chronic GVHD features).
• Marrow Failure
• Poor graft function in the presence of \>95% donor myeloid chimerism: defined as platelet or red cell transfusion dependent OR absolute neutrophil count persisting \<500/ (Micro)l for 14 days without other reversible or treatable causes.
• Pulmonary injury
• Hepatic injury
• Clinically diagnosed sinusoidal obstruction syndrome (SOS), previously known as veno-occlusive disease (VOD), with bilirubin \> 2 times ULN or transaminases \>3 times ULN and rising.
• Hemorrhagic cystitis (HC)
• HC requiring continuous bladder irrigation OR requiring red cell or platelet transfusions at least intermittently for the past 7 days OR HC unresponsive to antivirals after 10 days.
• Gastrointestinal tract
• Pneumoperitoneum, bowel perforation not susceptible to corrective surgery OR blood transfusion requirement \> 1 unit per day for 7 days.
• Age: greater than or equal to 18 years of age and less than or equal to 75 years of age.
• Birth Control

You may not qualify if:

• Breast feeding or pregnant females (due to unknown risk to fetus or newborn).
• Allergic to gentamicin
• Weight less than 20 kg (not informative for research sampling)
• Patients with significant organ failure at baseline as evidenced by any of the following:
• \<TAB\>Symptomatic cardiac failure at rest or with minimal activity or exertion for which intervention is indicated
• \<TAB\>Creatinine \> 3.0 X ULN
• \<TAB\>Decreased oxygen saturation at rest (e.g. pulse oximeter \< 88% or PaO2 less than or equal to 55 mmHg)

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Ogawa M, LaRue AC, Drake CJ. Hematopoietic origin of fibroblasts/myofibroblasts: Its pathophysiologic implications. Blood. 2006 Nov 1;108(9):2893-6. doi: 10.1182/blood-2006-04-016600. Epub 2006 Jul 13.

  PMID: 16840726 BACKGROUND

• Bhanu NV, Trice TA, Lee YT, Gantt NM, Oneal P, Schwartz JD, Noel P, Miller JL. A sustained and pancellular reversal of gamma-globin gene silencing in adult human erythroid precursor cells. Blood. 2005 Jan 1;105(1):387-93. doi: 10.1182/blood-2004-04-1599. Epub 2004 Sep 14.

  PMID: 15367428 BACKGROUND

• Taylor HS. Endometrial cells derived from donor stem cells in bone marrow transplant recipients. JAMA. 2004 Jul 7;292(1):81-5. doi: 10.1001/jama.292.1.81.

  PMID: 15238594 BACKGROUND

MeSH Terms

Conditions

Graft vs Host Disease

Condition Hierarchy (Ancestors)

Immune System Diseases

Study Officials

• Minocher M Battiwalla, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2012
• First Posted: July 4, 2012
• Study Start: November 14, 2011
• Primary Completion: July 1, 2013
• Study Completion: March 8, 2018
• Last Updated: December 12, 2019

Record last verified: 2018-03-08

Locations

US (1)