Transplantation of Partially Mismatched Related or Matched Unrelated Bone Marrow for Patients With Refractory Severe Aplastic Anemia

NCT02224872 | Completed Phase 2 Results DMC

• 2 other identifiers: J1424IRB00031590
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

Our primary objective is to determine if it is feasible for SAA patients to be transplanted using non-myeloablative conditioning and post transplantation cyclophosphamide with partially HLA-mismatched donors.

Conditions

Severe Aplastic Anemia; Bone Marrow Failure Syndromes

Keywords

bone marrow transplant; thymoglobulin; cyclophosphamide; fludarabine; tacrolimus; Mycophenolic Acid Mofetil; chemotherapy; GVHD; haploidentical

Outcome Measures

Primary Outcomes (1)

• Is This Type of Transplantation for Severe Aplastic Anemia Feasible and Safe?

  Feasibility will be met with the following conditions: the patient has the transplant, is assessed for the safety endpoint, and survives one year. The safety monitoring plan is included to monitor graft failure (day 60), grade 2-4 acute graft versus host disease (day100), 6 month mortality (day 180), and chronic graft versus host disease (day 180).

  1 year

Secondary Outcomes (10)

• Number of Patients That Have Survived at One Year

  1 year

• Number of Patients That Have Acheived Full Donor Chimerism by Day 60 After Transplant

  60 days

• Number of Patients That Expired Due to Non-relapsed-related Mortality Following Transplant

  1 year

• Number of Participants With Major Toxicities Related to Transplant

  1 year

• Number of Patients That Expired Due to Transplant Related Mortality

  1 year

Study Arms (1)

Bone marrow transplant

EXPERIMENTAL

Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35

Procedure: Bone marrow transplant; Drug: Thymoglobulin; Drug: Fludarabine; Drug: Cyclophosphamide; Radiation: TBI; Drug: Mesna; Drug: Tacrolimus; Drug: Mycophenolic acid mofetil

Interventions

Bone marrow transplant PROCEDURE

Day 0

Bone marrow transplant

Thymoglobulin DRUG

0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7

Bone marrow transplant

Fludarabine DRUG

30 mg/M2 IV on days -6 to -2

Bone marrow transplant

Cyclophosphamide DRUG

14.5 mg/kg IV on days -6, -5, 3, 4

Also known as: CTX

Bone marrow transplant

TBI RADIATION

200 cGy on day -1

Bone marrow transplant

Mesna DRUG

40 mg/kg IV on days 3, 4

Bone marrow transplant

Tacrolimus DRUG

For patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present

Bone marrow transplant

Mycophenolic acid mofetil DRUG

15 mg/kg PO/IV TID beginning on day 5 through day 35

Also known as: MMF

Bone marrow transplant

Eligibility Criteria

• Age: Up to 73 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with relapsed or refractory SAA or very SAA defined:
• Bone marrow (\< 25% cellular)
• Peripheral cytopenias (at least 2 of 3)
• ANC \< 500 per ml
• Platelets \< 20,000 per ml
• Absolute retic \< 60,000 or corrected retic \< 1%
• Very severe: as above, but ANC \< 200
• Disease may be designated as acquired or inherited if previous counts known (these other bone marrow failure disorders that are characterized by aplastic anemia may go by additional names such as dyskeratosis congenita or PNH)
• Failed at least one course of immunosuppressive therapy (if presumed acquired disease). Patients with inherited disease will be characterized as refractory and do not require immunosuppressive first.
• Age 0- upper age limit as determined by current institutional standards
• Good performance status (ECOG 0 or 1; Karnofsky and Lansky 70-100)
• Patients and donors must be able to sign consent forms (or if a minor the parent will sign). Donors should be willing to donate.
• Patients must be geographically accessible and willing to participate in all stages of treatment.
• Adequate end-organ function as measured by:
• Left ventricular ejection fraction \> or = to 35%, or shortening fraction \> 25% (For pediatric patients, a normal ejection fraction is required)

You may not qualify if:

• Patients will not be excluded on the basis of sex, racial or ethnic background.
• Prior transfusions from selected donor (as this could have cause recipient alloimmunization against the donor)
• Women of childbearing potential who currently are pregnant (HCG+) or who are not practicing adequate contraception.
• Patients who have any debilitating medical or psychiatric illness that would preclude their giving informed consent or their receiving optimal treatment and follow up.
• Uncontrolled viral, bacterial, or fungal infections (HIV infection permitted if viral load undetectable)

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead

Study Sites (2)

The Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287, United States

Location

Medical College of Wisconsin/Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• DeZern AE, Zahurak ML, Symons HJ, Cooke KR, Rosner GL, Gladstone DE, Huff CA, Swinnen LJ, Imus P, Borrello I, Wagner-Johnston N, Ambinder RF, Luznik L, Bolanos-Meade J, Fuchs EJ, Jones RJ, Brodsky RA. Haploidentical BMT for severe aplastic anemia with intensive GVHD prophylaxis including posttransplant cyclophosphamide. Blood Adv. 2020 Apr 28;4(8):1770-1779. doi: 10.1182/bloodadvances.2020001729.

  PMID: 32343796 DERIVED

MeSH Terms

Conditions

Anemia, Aplastic; Bone Marrow Failure Disorders

Interventions

Bone Marrow Transplantation; thymoglobulin; fludarabine; Cyclophosphamide; Mesna; Tacrolimus; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Amy DeZern
• Organization: Johns Hopkins University

Adezern1@jhmi.edu

4105027208

Study Officials

• Amy DeZern, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: August 18, 2014
• First Posted: August 25, 2014
• Study Start: August 1, 2014
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2021
• Last Updated: March 10, 2023
• Results First Posted: March 10, 2023

Record last verified: 2023-03

Locations

US (2)