A Phase II Trial of Non-Myeloablative Conditioning and Transplantation of Partially HLA-Mismatched/Haploidentical Related or Matched Unrelated Bone Marrow for Patients With Refractory Severe Aplastic Anemia and Other Bone Marrow Failure Syndromes

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

Sponsors

Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Source Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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.

Detailed Description

This research is being done to find out if bone marrow transplantation (BMT) followed by chemotherapy will help people with aplastic anemia who have failed other treatments.

You have a severe, life threatening disease (severe aplastic anemia) in your bone marrow. Your disease has come back or not responded after receiving one or more immunosuppressive treatments. High dose chemotherapy followed by bone marrow transplantation (BMT) has been used to treat blood diseases like yours but complications from Graft vs. Host disease (GVHD) and graft failure have limited the survival for those people.

A small study done at Johns Hopkins has shown that in subjects with other diseases (blood cancers) some immunosuppressive drugs given after the BMT have decreased how often subjects had complications of GVHD and engraftment failure.

People with aplastic anemia who have refractory disease (not responding to standard treatment) may join.

Overall Status Active, not recruiting
Start Date August 2014
Completion Date November 2023
Primary Completion Date November 2023
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Is this type of transplantation for SAA feasible and safe? 5 years
Secondary Outcome
Measure Time Frame
Number of patients that have survived at one year 5 years
Number of patients that have acheived full donor chimerism by day 60 after transplant 5 years
Number of patients that expired due to non-relapsed-related mortality following transplant 5 years
Major toxicities related to transplant 5 years
Number of patients that expired due to transplant related mortality 5 years
Number of patients with primary or secondary graft failure following transplant 5 years
Number of patients with grade II-IV or grade III-IV acute GVHD 5 years
Number of patients with chronic GVHD 5 years
Length of time required for patients to recover ANC and platelet counts after transplant 5 years
Length of GVHD free, relapse free survival (GRFS) in patients 5 years
Enrollment 18
Condition
Intervention

Intervention type: Procedure

Intervention name: Bone marrow transplant

Description: Day 0

Arm group label: Bone marrow transplant

Intervention type: Drug

Intervention name: Thymoglobulin

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

Arm group label: Bone marrow transplant

Intervention type: Drug

Intervention name: Fludarabine

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

Arm group label: Bone marrow transplant

Intervention type: Drug

Intervention name: Cyclophosphamide

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

Arm group label: Bone marrow transplant

Other name: CTX

Intervention type: Radiation

Intervention name: TBI

Description: 200 cGy on day -1

Arm group label: Bone marrow transplant

Intervention type: Drug

Intervention name: Mesna

Description: 40 mg/kg IV on days 3, 4

Arm group label: Bone marrow transplant

Intervention type: Drug

Intervention name: Tacrolimus

Description: 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

Arm group label: Bone marrow transplant

Intervention type: Drug

Intervention name: Mycophenolic acid mofetil

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

Arm group label: Bone marrow transplant

Other name: MMF

Eligibility

Criteria:

Inclusion Criteria:

- 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:

1. Left ventricular ejection fraction > or = to 35%, or shortening fraction > 25% (For pediatric patients, a normal ejection fraction is required)

2. Bilirubin ≤ 3.0 mg/dL (unless due to Gilbert's syndrome or hemolysis), and ALT and AST ≤ 5 x ULN

3. FEV1 and FVC > or = to 40% of predicted; or in pediatric patients, if unable to perform pulmonary function tests due to young age, oxygen saturation >92% on room air

Exclusion Criteria:

- 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)

Gender: All

Minimum age: N/A

Maximum age: 73 Years

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Amy DeZern, MD Principal Investigator Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Location
facility
The Sidney Kimmel Comprehensive Cancer Center | Baltimore, Maryland, 21287, United States
Medical College of Wisconsin/Children's Hospital of Wisconsin | Milwaukee, Wisconsin, 53226, United States
Location Countries

United States

Verification Date

January 2020

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Arm group label: Bone marrow transplant

Arm group type: Experimental

Description: 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

Study Design Info

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov