Trial of 2 Step ATG for Acute GVHD Prevention Post Myeloablative Allogeneic Stem Cell Transplant

Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-60
SponsorUniversity of Alabama at Birmingham

About this trial

The purpose of this study is to test whether the combination of the drugs called tacrolimus (Tac), methotrexate (MTX) and new dosing strategy of another drug called (rabbit Anti-thymocyte Globulin \[ATG\]) will help prevent the development and/or improve severity of acute and/or chronic GVHD.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Adult male or female, age 18-60 years

Patients must have a related or unrelated peripheral blood stem cell donor. Sibling donor must be a 6/6 match for HLA-A and -B at intermediate (or higher) resolution, and -DRB1 at high resolution using DNA-based typing, and must be willing to donate peripheral blood stem cells and meet institutional criteria for donation. Unrelated donor must be 8/8 match at HLA-A, -B, -C and -DRB1 at high resolution using DNA-based typing. Unrelated donor must be willing to donate peripheral blood stem cells and be medically eligible to donate stem cells according to NMDP criteria.

A candidate for Myeloablative preparative regimen, based on age ≤ 60, or HCT-CI of ≤ 4, and considered by the treating physician to be a candidate for such regimen.

Cardiac function: Ejection fraction ≥ 45%

Disqualifiers

Autologous hematopoietic stem cell transplant < 3 months prior to enrollment.

Patients with florid residual AML with > 5% blast in the marrow or circulating blast in the peripheral blood are not eligible for this study.

Previous allogeneic stem cell transplant.

Uncontrolled angina, severe uncontrolled ventricular arrhythmias, or EKG suggestive of acute ischemia or active conduction system abnormalities.

Trial design

Design model

Single group

Treatments tested in this trial

  • ATG Combined with Tacrolimus and Mini Methotrexate

    Drug

    On Day -7, subjects will be admitted to the hospital and receive a dose of prednisone at 1 mg/kg (ATG premedication). Subjects will receive a steroid injection 3 hours before every ATG infusion. On day -6, subjects will receive a small dose of ATG as an IV infusion. ATG will be repeated on days -5,-4 and -1. Routine transplant chemotherapy agent fludarabine will be given on days -6 to -2 as daily IV infusions. Busulfan, a routine transplant chemotherapy will be given on days -5 to -2 as IV infusion. Subjects with lymphoblastic leukemia will receive an alternative regimen of cyclophosphamide, a routine chemotherapy on days -6 and -5, followed by total body radiation on days -3 to -1. Tacrolimus (standard immune suppression agent) starts on day -3 as continuous IV infusion and switched to oral after engraftment. Methotrexate a standard immune suppression medication which is given IV on day +1,+3,+6, and +11 post-transplant. Blood draws on days -4,-1,+3,+7,+14 to measure ATG levels.

Treatment groups

29 Participants
are divided into 1 treatment group
Group A: phase II single arm study of 2 step ATG dosing in prevention of aGVHD.Experimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

To estimate the therapeutic success of 2-step ATG dosing platform in patients undergoing reduced intensity allogeneic transplantation for treatment of hematologic malignances

Rate of GRFS (graft versus host disease GVHD, relapse free survival) at one year post transplant. To meet that end point the patient needs to be alive without relapse, or grade III-IV acute GVHD, or chronic GVHD requiring systemic immune suppression.

Time frame
1 year post transplant

Secondary outcomes

Other outcomes

Sponsors and contacts

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