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Chemotherapy

GVHD-Reduction Strategies for Blood Cancers

Phase 2

Recruiting

Led By Marie Bleakley

Research Sponsored by Fred Hutchinson Cancer Research Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients aged 1-50 years old (inclusive) are eligible for TBI-based conditioning regimens

Patient age 1-60 years old (inclusive) at the time of informed consent

Must not have

Patients who have received previous myeloablative allogeneic or autologous transplantation.

DONOR: Donors who are HIV-1, HIV-2, HTLV-1, HTLV-2 seropositive or with active hepatitis B or hepatitis C virus infection. Test must be performed using Food and Drug Administration (FDA) licensed, cleared, and approved test kits (serological and/or nucleic acid amplification test [NAT] and/or other approved testing) in a Clinical Laboratory Improvement Act (CLIA)-certified laboratory.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up at 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing two different ways to reduce the risk of graft versus host disease.

Who is the study for?

This trial is for patients with acute leukemia or MDS in remission, aged 1-60, who have a matched donor for stem cell transplant. They must be vaccinated against COVID-19 and cannot participate if they weigh over 100 kg, are HIV positive, have significant organ dysfunction like kidney failure or heart issues, are pregnant/breastfeeding, unwilling to use birth control post-transplant, or have uncontrolled infections.

What is being tested?

The trial tests two strategies to reduce graft versus host disease after a donor peripheral blood stem cell transplant. Patients receive chemotherapy and total-body irradiation before the transplant to stop cancer growth and prepare their body to accept the donor's healthy stem cells.

What are the potential side effects?

Potential side effects include reactions from the immune system attacking normal tissues (graft versus host disease), complications from chemotherapy such as nausea and hair loss, risks associated with radiation exposure like fatigue and skin changes, and increased susceptibility to infections.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am between 1 and 50 years old and eligible for a specific treatment plan.

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I am between 1 and 60 years old.

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I have a donor who matches my HLA type for a stem cell donation.

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My leukemia is in remission with less than 5% marrow blasts.

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My donor is a perfect match for me based on detailed genetic testing.

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I have MDS with a history of high blast counts and received treatment within the last 3 months.

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I am between 1 and 60 years old and eligible for a specific chemotherapy regimen.

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I am a candidate for a specific stem cell transplant due to my diagnosis.

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My AML is in remission with less than 5% marrow blasts.

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I am willing to donate my stem cells.

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I am 18 years old or older.

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My leukemia is in remission with less than 5% of cancer cells in my bone marrow.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had a bone marrow transplant before.

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I am a donor without HIV, HTLV, active hepatitis B or C.

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My kidney function is reduced, but my creatinine clearance is above 60 ml/min.

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I have been told I have less than 12 months to live due to a condition other than my leukemia or MDS.

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I weigh less than 100 kg and have a donor who is a close genetic match.

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I am allergic to tacrolimus or methotrexate.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ at 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~at 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and at 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Graft versus host disease (GVHD)-free relapse-free survival (RFS)

Secondary study objectives

Graft rejection or irreversible graft failure (> 14 days duration)

Incidence of chronic GVHD

Overall survival (OS)

+1 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

6Treatment groups

Experimental Treatment

Group I: Arm D2 (busulfan, tacrolimus, methotrexate) [DISCONTINUED NOVEMBER 2021]Experimental Treatment11 Interventions

Patients receive busulfan IV over 180 minutes on days -8 to -5, cyclophosphamide IV over 1 hour on days -3 to -2, tacrolimus (or cyclosporine or sirolimus if toxicities occur) IV continuously starting on day -1, PBSC IV on day 0, and methotrexate IV on days 1, 3, 6, and 11. If there is no evidence of grade II-IV acute GVHD on or prior to day 50, tacrolimus (or cyclosporine or sirolimus) is tapered per month for capsules (or per week for liquid). Patients also undergo bone marrow aspiration/biopsy, ECHO or MUGA scan, and collection of blood samples throughout the trial.

Group II: Arm D1 (TBI, tacrolimus, methotrexate) [DISCONTINUED NOVEMBER 2021]Experimental Treatment11 Interventions

Patients undergo TBI BID on days -6 to -4, and receive cyclophosphamide IV over 1 hour on days -3 to -2, tacrolimus (or cyclosporine or sirolimus if toxicities occur) IV continuously starting on day -1, PBSC IV on day 0, and methotrexate IV on days 1, 3, 6, and 11. If there is no evidence of grade II-IV acute GVHD on or prior to day 50, tacrolimus (or cyclosporine or sirolimus) is tapered per month for capsules (or per week for liquid). Patients also undergo bone marrow aspiration/biopsy, ECHO or MUGA scan, and collection of blood samples throughout the trial.

Group III: Arm C2 (busulfan, PTCy, tacrolimus)Experimental Treatment11 Interventions

Patients receive fludarabine IV over 30 to 60 minutes on days -5 to -2, busulfan IV over 180 minutes on days -5 to -2, PBSC IV on day 0, cyclophosphamide IV over 1 to 2 hours on days 3 and 4, and tacrolimus (or cyclosporine or sirolimus if toxicities occur) IV continuously starting on day 5. If there is no evidence of grade II-IV acute GVHD on or prior to day 50, tacrolimus (or cyclosporine or sirolimus) is tapered per month for capsules (or per week for liquid). Patients also undergo bone marrow aspiration/biopsy, ECHO or MUGA scan, and collection of blood samples throughout the trial.

Group IV: Arm C1 (TBI, PTCy, tacrolimus)Experimental Treatment10 Interventions

Patients undergo TBI BID on days -4 to -2 or -3 to -1, and receive PBSC IV on day 0. Patients also receive cyclophosphamide IV over 1 to 2 hours on days 3 and 4, and tacrolimus (or cyclosporine or sirolimus if toxicities occur) IV continuously starting on day 5. If there is no evidence of grade II-IV acute GVHD on or prior to day 50, tacrolimus (or cyclosporine or sirolimus) is tapered per month for capsules (or per week for liquid). Patients also undergo bone marrow aspiration/biopsy, ECHO or MUGA scan, and collection of blood samples throughout the trial.

Group V: Arm A2 (busulfan, TnD)Experimental Treatment11 Interventions

Patients receive fludarabine IV over 30 to 60 minutes on days -6 to -2, busulfan IV over 180 minutes on days -5 to -2, and undergo TBI BID on day -1. Patients also receive tacrolimus (or cyclosporine or sirolimus if toxicities occur) IV continuously starting on day -1, CD34+ enriched CD45RA-depleted donor T-lymphocytes IV on day 0, and methotrexate IV on days 1, 3, 6, and 11. If there is no evidence of grade II-IV acute GVHD on or prior to day 50, tacrolimus (or cyclosporine or sirolimus) is tapered per month for capsules (or per week for liquid). Patients also undergo bone marrow aspiration/biopsy, ECHO or MUGA scan, and collection of blood samples throughout the trial.

Group VI: Arm A1 (TBI, TnD)Experimental Treatment12 Interventions

Patients undergo TBI BID on days -10 to -7, and receive thiotepa IV over 3 hours on days -6 and -5, fludarabine IV over 30 to 60 minutes on days -6 to -2, tacrolimus (or cyclosporine or sirolimus if toxicities occur) IV continuously starting on day -1, CD34+ enriched CD45RA-depleted donor T-lymphocytes IV on day 0, and methotrexate IV on days 1, 3, 6, and 11. If there is no evidence of grade II-IV acute GVHD on or prior to day 50, tacrolimus (or cyclosporine or sirolimus) is tapered per month for capsules (or per week for liquid). Patients also undergo bone marrow aspiration/biopsy, ECHO or MUGA scan, and collection of blood samples throughout the trial.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Echocardiography

2013

Completed Phase 4

~11580

Fludarabine

2012

Completed Phase 4

~1860