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GVHD Prophylaxis Regimens for Blood Cancer Stem Cell Transplant

Phase 2

Waitlist Available

Led By Masumi Ueda Oshima

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

Waldenstrom's macroglobulinemia - must have failed 2 courses of therapy

Mismatched for two HLA class I alleles, but matched for HLA-DRB1 and HLA-DQ

Must not have

Patients with rapidly progressive intermediate or high grade NHL

Presence of >= 5% circulating leukemic blasts (in the blood) detected by standard pathology for patients with MDS/MPS/CMML

Timeline

Screening 3 weeks

Treatment Varies

Follow Up at 1 year post-hct

Awards & highlights

No Placebo-Only Group

Summary

This trial is studying two different drug combinations to reduce the risk of a common but serious complication called "graft versus host disease" (GVHD) following a blood stem cell transplant from an unrelated donor to treat blood cancer.

Who is the study for?

Adults aged 18-50 with certain high-risk blood cancers treatable by stem cell transplant from an unrelated donor, but who can't handle high-dose transplants due to medical conditions or prior therapy. Specific criteria include having less than 5% marrow blasts for some leukemias and being in remission for others. Must not be pregnant, breastfeeding, have severe organ dysfunction or active infections unresponsive to treatment.

What is being tested?

This phase II trial tests a lower dose of chemotherapy combined with a blood stem cell transplant from an unrelated donor to treat various blood cancers. It compares two drug combinations (CSP+SIR+MMF vs CSP+SIR+PTCy) aiming to reduce graft versus host disease risk after the transplant.

What are the potential side effects?

Potential side effects may include immune system suppression leading to increased infection risk, liver and kidney function impairment, gastrointestinal issues like nausea and diarrhea, mouth sores, fatigue, and possible allergic reactions to the drugs used.

Eligibility Criteria

Inclusion Criteria

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

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I have Waldenstrom's macroglobulinemia and two treatments have not worked for me.

Select...

My donor and I mismatch for two HLA class I alleles but match for HLA-DRB1 and HLA-DQ.

Select...

I am 18-50 years old with a blood disease, at high risk due to my medical history.

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My donor is a partial match for my transplant.

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My donor is a match for HLA class I and may have up to two mismatches in DRB1 or DQB1.

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My donor is not a full HLA match but matches at key HLA points.

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

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I have CML and either TKIs didn't work for me or I couldn't tolerate them.

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My genetic match for the transplant is nearly perfect, with only one minor difference.

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My donor and I do not have a two-allele mismatch.

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I am between 18 and 50 years old with chronic lymphocytic leukemia.

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My leukemia has less than 5% marrow blasts before transplant.

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My stem cell donor will use G-CSF for stem cell collection.

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My BPDCN is currently in complete remission.

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My donor and I are a close match for bone marrow transplant.

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My Hodgkin lymphoma did not respond to the first treatment I received.

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I have an aggressive type of non-Hodgkin lymphoma and am not a candidate for certain stem cell transplants.

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I am over 50 and have a blood cancer treatable by a stem cell transplant.

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I am between 18-50 years old and need a transplant for my blood disease but refuse high-dose treatment.

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My leukemia has less than 5% marrow blasts before transplant.

Exclusion Criteria

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

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My lymphoma is fast-growing and not low grade.

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My blood has at least 5% leukemia cells.

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I have high blood pressure that isn't well-controlled despite taking several medications.

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I have an infection that hasn't improved with treatment.

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I have CMML and haven't had induction chemotherapy.

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I have MDS-EB or AML and haven't had strong chemotherapy or a specific treatment regimen.

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My blood test shows cancer cells for AML, ALL, or CML.

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I am not willing to use birth control during and for a year after treatment.

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I have a fungal infection that didn't improve after 1 month of specific treatment.

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My lung function is severely impaired or I need extra oxygen.

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My liver functions normally without serious diseases like cirrhosis or severe hepatitis.

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My donor's HLA type does not match mine exactly at a specific genetic spot.

Select...

My brain or spinal cord cancer hasn't responded to chemotherapy in the spine.

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I am not pregnant or breastfeeding.

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My health severely limits my ability to care for myself.

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I am currently receiving hemodialysis.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ at 1 year post-hct

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~at 1 year post-hct

This trial's timeline: 3 weeks for screening, Varies for treatment, and at 1 year post-hct for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Chronic graft versus host disease (GVHD)-free, relapse-free survival (CRFS)

Secondary study objectives

Bone Transplantation

Late graft versus host disease (GVHD) not meeting National Institute of Health (NIH) consensus criteria for chronic GVHD

Moderate and severe chronic graft versus host disease

+4 more

Side effects data

From 2019 Phase 2 trial • 77 Patients • NCT01251575

Hypoxia

Febrile neutropenia

Acute kidney injury

Blood bilirubin increased

Diarrhea

Creatinine increased

Sepsis

Hypotension

Left ventricular systolic dysfunction

Bronchopulmonary hemorrhage

Chronic kidney disease

Thromboembolic event

Lung infection

Atrial fibrillation

Atrial flutter

Hemolysis

Hemolytic uremic syndrome

Ejection fraction decreased

Encephalitis infection

Gastric hemorrhage

Gastritis

Heart failure

Mucositis oral

Multi-organ failure

Myalgia

Pleural effusion

Respiratory failure

Small intestine infection

Syncope

Treatment related secondary malignancy

Typhlitis

Fever

Paroxysmal atrial tachycardia

Ascites

100%

80%

60%

40%

20%

Study treatment Arm

Treatment (Fludarabine, Transplant, Immunosuppression)

Awards & Highlights

No Placebo-Only Group

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

Trial Design

2Treatment groups

Experimental Treatment

Group I: Arm II (cyclosporine, sirolimus, cyclophosphamide)Experimental Treatment4 Interventions

Patients undergo HCT at day 0. Patients with an HLA-matched unrelated donor receive cyclosporine PO BID on days 5-96 then tapered to day 150, sirolimus PO QD on days 5-150 then tapered to day 180, and cyclophosphamide IV on days 3 and 4. Patients with an HLA-mismatched donor receive cyclosporine PO BID on days 5-150 then tapered to day 180, sirolimus PO QD on days 5-180 then tapered to day 365, and cyclophosphamide IV on days 3 and 4.

Group II: Arm I (mycophenolate mofetil, cyclosporine, sirolimus)Experimental Treatment4 Interventions

Patients undergo allogeneic HCT at day 0. Patients with an HLA-matched unrelated donor receive mycophenolate mofetil PO on days 0 to 40, cyclosporine PO every 12 hours BID on days -3 to 96 then tapered to day 150, and sirolimus PO QD on days -3 to day 150 then tapered to day 180. Patients with an HLA-mismatched donor receive mycophenolate mofetil PO on days 0-100 then tapered to day 150, cyclosporine PO BID on days -3 to 150 then tapered to day 180, and sirolimus PO QD on days -3 to 180 then tapered to day 365.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cyclophosphamide

2010

Completed Phase 4

~2310

Cyclosporine

1997

Completed Phase 3

~1820