Clinical trial NCT01940796: Phase I Trial of Brentuximab Vedotin for Refractory Chronic Graft-vs.-Host Disease (GVHD)
Official title: Phase I Trial of Brentuximab Vedotin for Refractory Chronic Graft-vs.-Host Disease (GVHD)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Graft-vs-Host Disease
GVHD
Keywords: Brentuximab Vedotin
GVHD
Refractory Chronic Graft vs Host Disease
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Seagen Inc.
First posted: 2013-09-12
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This research study is trying to determine the safest dose of Brentuximab Vedotin that can be given to patients with chronic GVHD and see if chronic GVHD improves.

Detailed description: This study is looking for the highest dose of the Brentuximab Vedotin that can be administered safely without severe or unmanageable side effects in patients that have chronic Graft vs. Host Disease, not everyone who participates in this research study will receive the same dose of the study drug. The dose each patient will get depends on the number of participants who have been enrolled in the study prior and how well they have tolerated their doses.

Each patient will receive a dose of Brentuximab Vedotin every 3 weeks. Brentuximab Vedotin is administered via intravenous infusion, or IV infusion, which means directly into the vein, over a period of about 30 minutes.

Each cycle is 21 days long.

Each patient will undergo the following tests and procedures when they come into the clinic to receive each dose of Brentuximab Vedotin:

Days 1, 8, and 15 of 1st 2 cycles:

* Physical exam, which includes height, weight, body surface area and vital signs.
* A medical history, which includes questions about your health, current medications, and any allergies.
* Performance status, which evaluates how participant are able to carry on with your usual activities.
* Routine blood tests to test overall health (about 1 teaspoon of blood) Assessment of side effects- physician will evaluate the patient's current health and ask questions to see there are any experienced side effects from taking the study drug.

Only Day 1 of 1st 3 cycles:

* Research blood draws for biomarker and PK assessments (pharmacokinetic assessments that measure the level of drug in the patient's blood) (about 4 teaspoons of blood)
* Biomarker studies blood draw (about 4 teaspoons) Viral monitoring blood tests to make sure each patient has not developed any new viruses as a result of treatment (about 4 teaspoons of blood)
* Chronic GVHD assessments: The patient's physician may need to perform other tests to confirm the diagnosis of acute GVHD. These can include more blood tests, imaging studies, and possibly biopsies of affected organs. The exact tests will be determined by the patient's physician

Planned Follow-up: If the patient's physician believes the patient is responding well to treatment, the patient may receive up to 16 cycles of Brentuximab Vedotin. The Investigator would like to keep track of patient's medical condition for 12 months after the patient has completed the first 2 cycles of treatment, no matter if the patient receives more doses or not. The Investigator would like to do this by calling the patient on the telephone to see how he/she is doing. Keeping in touch with patient and checking the condition helps the Investigator look at the long-term effects of the research study.

Eligibility criteria: Inclusion Criteria:

* Recipients of allogeneic hematopoietic cell transplantation (HCT) after either myeloablative or reduced intensity conditioning regimens. Any donor source of stem cells is eligible.
* Participants must be at least 100 days after HCT.
* Patients must have steroid refractory cGVHD, defined as having persistent signs and symptoms of chronic GVHD (section 13.1) despite the use of prednisone at ≥ 0.25 mg/kg/day (or 0.5 mg/kg every other day) for at least 4 weeks in the preceding 12 months (or equivalent dosing of alternate corticosteroids) without complete resolution of signs and symptoms.
* Stable dose of corticosteroids for 4 weeks prior to enrollment
* No addition or subtraction of other immunosuppressive medications (e.g., calcineurin inhibitors, sirolimus, mycophenolate mofetil) for 4 weeks prior to enrollment. The dose of immunosuppressive medicines may be adjusted based on the therapeutic range of that drug
* Serum Cr ≤ 3 gm / dL
* Adequate hepatic function (total bilirubin \< 2.0 mg/dl, AST \< 5x ULN), unless hepatic dysfunction is a manifestation of presumed cGVHD. For patients with abnormal LFTs as the sole manifestation of active cGVHD, documented cGVHD on liver biopsy will be required prior to enrollment. Abnormal LFTs in the context of active cGVHD involving other organ systems may also be permitted if the treating physician documents the abnormal LFTs as being consistent with active hepatic cGVHD, and a liver biopsy will not be mandated in this situation.
* Patients must have adequate bone marrow function as defined by ANC ≥ 1000 / µl and platelets ≥ 20,000 / µl without growth factor or transfusional support
* Negative pregnancy test for females of child bearing age
* Age ≥ 18 - The safety and effectiveness of brentuximab vedotin has not been established in the pediatric population. Clinical trials of brentuximab vedotin included only 9 pediatric patients and this number is not sufficient to determine whether they respond differently than adult patients.
* The effects of brentuximab vedotin on the developing human fetus are unknown. For this reason and because chemotherapy agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
* Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* Ongoing prednisone requirement \> 1 mg/kg/day (or equivalent)
* Exposure to any new immunosuppressive medication in the 4 weeks prior to enrollment.
* ECP therapy within 4 weeks prior to enrollment
* Active malignant disease relapse
* Active, uncontrolled infection
* Uncontrolled cardiac angina or symptomatic congestive heart failure (NYHA Class III or IV).
* Karnofsky performance status \< 30
* Prior use of brentuximab vedotin for GVHD is not allowed. Prior use of brentuximab vedotn for the treatment of malignancy is allowed.
* Pregnant women are excluded from this study because brentuximab vedotin is a chemotherapy agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with brentuximab vedotin, breastfeeding should be discontinued if the mother is treated with brentuximab vedotin.

Primary outcomes:
measure: To define the maximum tolerated dose (MTD) of brentuximab vedotin when given as treatment for refractory chronic GVHD
timeFrame: 2 Years
Secondary outcomes:
measure: To test the overall response rate of Brentuximab Vedotin when given as treatment for refractory chronic GVHD
timeFrame: 2 Years
measure: To identify the toxicities associated with Brentuximab Vedotin when used as therapy for refractory chronic GVHD
timeFrame: 2 Years
measure: Overall Survival
timeFrame: 2 Years
measure: To assess levels of soluble CD30 and surface CD30 expression on peripheral blood T-cells in participants with chronic GVHD before and after the administration of brentuximab vedotin
timeFrame: 2 Years
measure: To assess dose of steroids (mg/kg/day of prednisone equivalent) at 6 and 12 months after starting therapy
timeFrame: 2 Years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Yi-Bin Chen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chen YB, Perales MA, Li S, Kempner M, Reynolds C, Brown J, Efebera YA, Devine SM, El-Jawahri A, McAfee SL, Spitzer TR, Soiffer RJ, Ritz J, Cutler C. Phase 1 multicenter trial of brentuximab vedotin for steroid-refractory acute graft-versus-host disease. Blood. 2017 Jun 15;129(24):3256-3261. doi: 10.1182/blood-2017-03-772210. Epub 2017 May 4.