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Alkylating agents

Bendamustine +/- Cyclophosphamide to Prevent GVHD Post Stem Cell Transplant for Blood Cancers

Phase 1 & 2

Recruiting

Led By Issa F Khouri

Research Sponsored by M.D. Anderson Cancer Center

Eligibility Criteria Checklist

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

Must have

Zubrod performance 0 to 2 or Karnofsky of at least 60.

Creatinine less than or equal to 1.6 mg/dL and creatinine clearance >= 30 ml/min. Creatine clearance will be calculated using the Cockcroft-Gault equation. (at time of study entry)

Must not have

Toxicities (grade > 1) unresolved from prior treatment (including chemotherapy, targeted therapy, immunotherapy, experimental agents radiation, or surgery.

Known to be human immunodeficiency virus (HIV) positive.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing bendamustine, with or without cyclophosphamide, to see if it can help prevent GVHD in patients undergoing stem cell transplant.

Who is the study for?

This trial is for blood cancer patients who need a stem cell transplant and have good lung function (FVC and FEV1 >= 40%), heart function (ejection fraction >= 40%), and kidney function (creatinine clearance >= 30 ml/min). They must have a donor that's mismatched or haplo-identical, be relatively fit (Zubrod performance 0 to 2 or Karnofsky ≥60), not HIV positive, without active hepatitis B/C, unresolved toxicities from prior treatments, certain active diseases/infections, or pregnant/nursing.

What is being tested?

The study tests if bendamustine with/without cyclophosphamide can prevent GVHD after stem cell transplants. It includes chemotherapy drugs like melphalan and fludarabine, total-body irradiation before the transplant to kill cancer cells/make room for new cells in bone marrow, followed by tacrolimus and mycophenolate mofetil to potentially stop GVHD.

What are the potential side effects?

Possible side effects include reactions from chemotherapy such as nausea, fatigue, hair loss; organ inflammation due to immune response; increased risk of infections post-transplant; complications from radiation like skin irritation; plus potential issues related to immunosuppressants such as tacrolimus.

Eligibility Criteria

Inclusion Criteria

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

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I can take care of myself but may not be able to do heavy physical work.

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My kidney function, measured by creatinine levels, is within the required range.

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I have a blood cancer.

Exclusion Criteria

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

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I have no lasting side effects above mild from previous cancer treatments.

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I am HIV positive.

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I am unable or unwilling to sign the consent form.

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I have active hepatitis B or C.

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I do not have any active or uncontrolled infections.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 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

Incidence of adverse events (Phase II)

Maximum tolerated dose level (MTDL) (Phase I)

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: Schedule II (lymphoid malignancies)Experimental Treatment9 Interventions

Patients receive fludarabine IV over 1 hour, bendamustine IV over 30-60 minutes on days -5 to -3 and undergo TBI on day -1 and stem cell transplantation over 2-6 hours on day 0. Depending on when the trial was joined, patients receive cyclophosphamide IV over 3 hours or bendamustine IV over 30-60 minutes or cyclophosphamide IV over 3 hours and bendamustine IV over 30-60 minutes on day 3. Patients also receive bendamustine IV over 30-60 minutes on day 4. Beginning day 5, patients receive tacrolimus IV followed by PO QD or BID for 6 months and mycophenolate mofetil PO TID until day 100. Beginning day 7, patients receive filgrastim-sndz SC QD until blood cell levels return to normal. CD20+ patients receive rituximab IV over 4-6 hours on days -13, -6, 1, and 8.

Group II: Schedule I (non-lymphoma)Experimental Treatment9 Interventions

Patients receive fludarabine IV over 1 hour on days -5 to -2, melphalan IV over 30 minutes on days -5 and -4, and undergo TBI on day -1 and stem cell transplantation IV over 2-6 hours on day 0. Depending on when the trial was joined, patients receive cyclophosphamide IV over 3 hours or bendamustine IV over 30-60 minutes or cyclophosphamide IV over 3 hours and bendamustine IV over 30-60 minutes on day 3. Patients also receive bendamustine IV over 30-60 minutes on day 4. Beginning day 5, patients receive tacrolimus IV followed by PO QD or BID for 6 months and mycophenolate mofetil PO TID until day 100. Beginning day 7, patients receive filgrastim-sndz SC QD until blood cell levels return to normal.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Allogeneic Hematopoietic Stem Cell Transplantation

2012

Completed Phase 2

~1240

Bendamustine

2015

Completed Phase 3

~3230