Hematologic MalignancyPhase 2NCT03699631
PROACTIVE: Preventing Acute/Chronic GVHD With TocIlizumab Combined With GVHD Prophylaxis Post allogEneic Transplant
A Phase 2 study testing Tacrolimus, Methotrexate and Tocilizumab in people with Hematologic Malignancy, run by Medical College of Wisconsin at 1 site in United States.
Trial summary
This is a phase II open-label trial designed to evaluate the efficacy of tocilizumab in improving GVHD-free/relapse-free survival (GRFS) after allogeneic hematopoietic cell transplantation (alloHCT) for hematologic malignancy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hematologic Malignancy
- What is being tested?
- Tacrolimus, Methotrexate and Tocilizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Nov 2018to 1 Apr 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years.
- Patients with any hematologic malignancy for which alloHCT is indicated. Patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) must be in complete remission at the time of alloHCT(<5% blasts in the bone marrow, normal maturation of all cellular components in the bone marrow and absence of extramedullary disease).
- Myeloablative conditioning (MAC) regimen, based on Center for International Blood and Marrow Transplant Research (CIBMTR) criteria.
- T cell-replete peripheral blood graft.
- Patients must have a matched related or unrelated donor (at least 6/6 match at human leukocyte antigens (HLA) -A, -B and -C for related donors and at least 8/8 match at HLA-A, -B, -C and -DRB1 for unrelated donors).
- Cardiac function: Left ventricular ejection fraction ≥45% for myeloablative conditioning.
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- Estimated creatinine clearance ≥40 mL/minute (using the Cockcroft-Gault formula and actual body weight).
- Pulmonary function: Diffusing capacity of the lungs for carbon monoxide (DLCO) ≥40% (adjusted for hemoglobin) and Forced Expiratory Volume (FEV1) ≥50%.
- Liver function: total bilirubin <3 x upper limit of normal and alanine aminotransferase (ALT) / aspartate aminotransferase (AST) <5 x upper normal limit.
- Signed informed consent: Voluntary written consent must be given before patient registration and performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
- Female patient: A negative pregnancy test will be required for women of child bearing potential. Breast-feeding or lactation is not permitted.
- Planned posttransplant maintenance therapy is allowed.
Who cannot join
- Prior allogeneic HCT.
- Active central nervous system (CNS) involvement with malignancy.
- Patients receiving cord blood or haploidentical allograft.
- Patients undergoing in vivo or ex vivo T cell-depleted alloHCT.
- Karnofsky Performance Score <60%.
- Patients with uncontrolled bacterial, viral or fungal infections (currently on treatment and with progression of infectious disease or no clinical improvement) at time of enrollment.
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- Active hepatitis B or C virus infection or known human immunodeficiency virus (HIV) positive.
- Prior intolerance or allergy to tocilizumab.
- Use of rituximab, alemtuzumab, anti-thymocyte globulin (ATG) or other monoclonal antibody planned as part of conditioning regimen for GVHD prophylaxis.
- History of diverticulitis, Crohn's disease or ulcerative colitis.
- History of demyelinating disorder.
- Any current uncontrolled cardiovascular conditions, including uncontrolled ventricular arrhythmias, New York Heart Association (NYHA) class III or IV congestive heart failure, uncontrolled angina, or electrocardiographic evidence of active ischemia or active conduction system abnormalities.
- Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: PROACTIVE: Prevention of Acute and Chronic GVHD Using TocIlizumab in Combination With Standard GVHD Prophylaxis After allogEneic Transplantation
This is a phase II open-label trial designed to evaluate the efficacy of tocilizumab in improving GVHD-free/relapse-free survival (GRFS) after allogeneic hematopoietic cell transplantation (alloHCT) for hematologic malignancy.
Read the detailed description
The research team earlier hypothesized and demonstrated that tocilizumab could attenuate the incidence of acute GVHD (aGVHD) after myeloablative conditioning (MAC) and reduced intensity conditioning (RIC) Allogeneic hematopoietic cell transplantation (alloHCT), using matched sibling or unrelated donor. In this study, the research team hypothesizes that longer term interleukin 6 (IL-6) inhibition through treatment with tocilizumab by repeated dosing would mediate a beneficial effect not only on the risk of aGVHD, but also on chronic GVHD. This will be achieved by administering an additional dose of tocilizumab at Day +100 post-alloHCT, besides the pretransplant dose, as done in our previous clinical trial, thereby providing total prophylaxis against both acute and chronic GVHD.
- Conditions
- Hematologic Malignancy
- Being tested
- Tacrolimus, Methotrexate, Tocilizumab
- Medical subject headings
- Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TacrolimusDrug
Also called Prograf
Tacrolimus will be given intravenously at a dose of 0.03 mg/kg/day starting Day -3. Subsequent dosing will be based on blood levels.
MethotrexateDrug
Also called Trexall
Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic cell infusion.
TocilizumabDrug
Also called Actemra
Tocilizumab will be administered intravenously (IV) at a dose of 8 mg/kg (maximum dose of 800 mg) once on the Day -1 approximately 24 hours prior to the estimated time of the hematopoietic cell infusion, and subsequently, on Day +100 (+/- 14 days, i.e., Days +86 to +114) post-alloHCT. The infusion will be administered over 60 minutes through a dedicated IV line and must not be administered by IV bolus.
| Study group | Role | What they receive |
|---|---|---|
| Tacrolimus/Methotrexate/Tocilizumab | Experimental | Patients enrolled on the clinical trial will receive tacrolimus initiating at Day -1 at doses to maintain therapeutic levels per institutional preference and continued until at least Day +90 post-transplant.
Methotrexate will be administered intravenously and dosed at 15 mg/m2 Day +1 and 10 mg/m2 Days +3, +6 and +11.
Tocilizumab will be administered intravenously at a dose of 8 mg/kg on Day -1 and at day +100 (+/- 14 days). Receives: Drug: Tacrolimus; Drug: Methotrexate; Drug: Tocilizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Number of Patients With GVHD/Relapse-free (GRFS) Survival
GRFS is defined as survival without grade III-IV acute graft versus host disease (GVHD), systemic therapy requiring chronic GVHD, relapse, or death at 12 months after matched related/unrelated donor bone marrow or peripheral blood allogeneic hematopoietic cell transplantation (alloHCT) using myeloablative conditioning (MAC). Patients who are alive without GVHD will be censored at the last follow-up.
Measured: Day 365
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2018
- Study start6 Nov 2018
- Primary completion2 Mar 2022
- Study completion1 Apr 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hematologic MalignancyStudies of the same condition, open and under way.
- More trials run by Medical College of WisconsinThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical College of Wisconsin
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, William R. Drobyski, MD, Medical College of Wisconsin
- Investigators
- William R Drobyski, MD, Principal investigator, Medical College of Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03699631
- Sponsor's protocol ID
- PRO32694
- Other IDs
- 1K08HL143189-01A1, 5P30CA008748
- Status last verified
- Apr 2023
- First submitted
- 5 Oct 2018
- Last updated
- 19 Apr 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Chhabra S, Szabo A, Clurman A, McShane K, Waters N, Eastwood D, Samanas L, Fei T, Armijo G, Abedin S, Longo W, Hari P, Hamadani M, Shah NN, Runaas L, Jerkins JH, Van den Brink M, Peled JU, Drobyski WR. Mitigation of gastrointestinal graft-versus-host disease with tocilizumab prophylaxis is accompanied by preservation of microbial diversity and attenuation of enterococcal domination. Haematologica. 2023 Jan 1;108(1):250-256. doi: 10.3324/haematol.2022.281309. No abstract available.
PubMed 36106394
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PROACTIVE: Prevention of Acute and Chronic GVHD Using TocIlizumab in Combination With Standard GVHD Prophylaxis After allogEneic Transplantation
- ClinicalTrials.gov ID
- NCT03699631
- Acronym / sponsor ID
- PRO32694
- Conditions
- Hematologic Malignancy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Medical College of WisconsinUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), National Cancer Institute (NCI)
- Study start
- 6 Nov 2018 (actual)
- Primary completion
- 2 Mar 2022 (actual)
- Study completion
- 1 Apr 2023 (actual)
- First posted
- 9 Oct 2018 (actual)
- Results
- Posted 19 Apr 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase II open-label trial designed to evaluate the efficacy of tocilizumab in improving GVHD-free/relapse-free survival (GRFS) after allogeneic hematopoietic cell transplantation (alloHCT) for hematologic malignancy.
Detailed description
The research team earlier hypothesized and demonstrated that tocilizumab could attenuate the incidence of acute GVHD (aGVHD) after myeloablative conditioning (MAC) and reduced intensity conditioning (RIC) Allogeneic hematopoietic cell transplantation (alloHCT), using matched sibling or unrelated donor. In this study, the research team hypothesizes that longer term interleukin 6 (IL-6) inhibition through treatment with tocilizumab by repeated dosing would mediate a beneficial effect not only on the risk of aGVHD, but also on chronic GVHD. This will be achieved by administering an additional dose of tocilizumab at Day +100 post-alloHCT, besides the pretransplant dose, as done in our previous clinical trial, thereby providing total prophylaxis against both acute and chronic GVHD.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tacrolimus/Methotrexate/Tocilizumab | Experimental | Drug: Tacrolimus, Drug: Methotrexate, Drug: TocilizumabPatients enrolled on the clinical trial will receive tacrolimus initiating at Day -1 at doses to maintain therapeutic levels per institutional preference and continued until at least Day +90 post-transplant. Methotrexate will be administered intravenously and dosed at 15 mg/m2 Day +1 and 10 mg/m2 Days +3, +6 and +11. Tocilizumab will be administered intravenously at a dose of 8 mg/kg on Day -1 and at day +100 (+/- 14 days). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Age ≥18 years.
- Patients with any hematologic malignancy for which alloHCT is indicated. Patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) must be in complete remission at the time of alloHCT(<5% blasts in the bone marrow, normal maturation of all cellular components in the bone marrow and absence of extramedullary disease).
- Myeloablative conditioning (MAC) regimen, based on Center for International Blood and Marrow Transplant Research (CIBMTR) criteria.
- T cell-replete peripheral blood graft.
- Patients must have a matched related or unrelated donor (at least 6/6 match at human leukocyte antigens (HLA) -A, -B and -C for related donors and at least 8/8 match at HLA-A, -B, -C and -DRB1 for unrelated donors).
Key exclusion criteria (13 listed)
- Prior allogeneic HCT.
- Active central nervous system (CNS) involvement with malignancy.
- Patients receiving cord blood or haploidentical allograft.
- Patients undergoing in vivo or ex vivo T cell-depleted alloHCT.
- Karnofsky Performance Score <60%.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TacrolimusAlso: PrografTacrolimus will be given intravenously at a dose of 0.03 mg/kg/day starting Day -3. Subsequent dosing will be based on blood levels. | Drug | Tacrolimus/Methotrexate/Tocilizumab |
| MethotrexateAlso: TrexallMethotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic cell infusion. | Drug | Tacrolimus/Methotrexate/Tocilizumab |
| TocilizumabAlso: ActemraTocilizumab will be administered intravenously (IV) at a dose of 8 mg/kg (maximum dose of 800 mg) once on the Day -1 approximately 24 hours prior to the estimated time of the hematopoietic cell infusion, and subsequently, on Day +100 (+/- 14 days, i.e., Days +86 to +114) post-alloHCT. The infusion will be administered over 60 minutes through a dedicated IV line and must not be administered by IV bolus. | Drug | Tacrolimus/Methotrexate/Tocilizumab |
Primary outcome
The Number of Patients With GVHD/Relapse-free (GRFS) Survival
Time frame: Day 365
GRFS is defined as survival without grade III-IV acute graft versus host disease (GVHD), systemic therapy requiring chronic GVHD, relapse, or death at 12 months after matched related/unrelated donor bone marrow or peripheral blood allogeneic hematopoietic cell transplantation (alloHCT) using myeloablative conditioning (MAC). Patients who are alive without GVHD will be censored at the last follow-up.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 36106394Chhabra S, Szabo A, Clurman A, McShane K, Waters N, Eastwood D, Samanas L, Fei T, Armijo G, Abedin S, Longo W, Hari P, Hamadani M, Shah NN, Runaas L, Jerkins JH, Van den Brink M, Peled JU, Drobyski WR. Mitigation of gastrointestinal graft-versus-host disease with tocilizumab prophylaxis is accompanied by preservation of microbial diversity and attenuation of enterococcal domination. Haematologica. 2023 Jan 1;108(1):250-256. doi: 10.3324/haematol.2022.281309. No abstract available.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
William R Drobyski, MD principal investigator
Medical College of Wisconsin
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tacrolimus, Methotrexate and Tocilizumab in people with Hematologic Malignancy, run by Medical College of Wisconsin at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Apr 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Number of Patients With GVHD/Relapse-free (GRFS) Survival (time frame: Day 365). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03699631, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2023.