Acute LeukemiaPhase 1NCT03588936
Nivolumab and Tocilizumab for Relapsed Hematological Malignancy Post-allogeneic Transplant
A Phase 1 study testing Nivolumab (.25 mg/kg), Tocilizumab and Nivolumab (.5 mg/kg) in people with Acute Leukemia and Chronic Leukemia, run by Medical College of Wisconsin at 1 site in United States.
Trial summary
This is a phase 1, interventional single arm, open label, treatment study designed to evaluate the safety combination programmed cell death protein 1 (PD-1) and interleukin 6 (IL-6) inhibition in participants with relapsed disease post-allogeneic transplant. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Leukemia, Chronic Leukemia, Lymphoma
- What is being tested?
- Nivolumab (.25 mg/kg), Tocilizumab and Nivolumab (.5 mg/kg)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Sep 2018to 15 Jul 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 with hematological malignancies who have undergone allogeneic transplant for hematological malignancy and are ≥180 days post-transplant.
- Relapsed disease post-allogeneic transplant defined as follows i. Acute or Chronic Leukemia or myelodysplastic or myeloproliferative disorders or natural killer (NK) cell neoplasms: Bone marrow (BM) with ≥5% disease involvement or peripheral blood evidence of overt relapse ii. Lymphoma: BM evidence of relapsed/persistent disease or PET/CT or CT evidence of persistent/progressive lymphadenopathy consistent with active lymphoma. Active disease defined as nodal lesions ≥ 20 mm in the long axis or extranodal lesions≥10 mm in long and short axis or bone marrow involvement that is biopsy proven
- Karnofsky performance status ≥70 (See Appendix A for details)
- Creatinine Clearance≥60 ml/min
- Adequate hepatic function, defined as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 x upper limit of normal (ULN). Serum bilirubin and alkaline phosphatase ≤3x x ULN, or considered not clinically significant (e.g. Gilbert's or indirect hyperbilirubinemia) or felt to be due to underlying disease.
- Without evidence of active acute or chronic graft versus host disease (GVHD)
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- Off all immunosuppression and corticosteroids (other than replacement dose steroids defined as equivalent to a maximum of 10 mg Prednisone daily) for ≥28 days from first treatment.
- Off all disease targeted treatments for ≥10 days to first treatment day
- Able to provide written informed consent
- Women of child-bearing potential and men must agree to use adequate contraception for the duration of study participation and for 120 days after the last treatment with nivolumab.
- No FDA approved, more appropriate therapies available for disease control as determined by the treating physician
Who cannot join
- Positive beta-human chorionic gonadotropin (HCG) in female of child-bearing potential
- Cluster of differentiation 3 (CD3) donor chimerism <5% within 4 weeks of starting study treatment
- Prior administration of donor lymphocyte infusion post-allogeneic transplant within the last 6 months of study treatment
- History of or active autoimmune disease, or other syndrome that requires systemic steroids.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab.
- Uncontrolled or active infections on treatment
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- Confirmed active human immunodeficiency virus (HIV), Hepatitis B or C infection.
- Presence of ≥grade 3 non-hematologic toxicities as per CTCAE version 5 from any previous treatment unless it is felt to be due to underlying disease.
- Concurrent use of investigational therapeutic agents or enrollment on another therapeutic clinical trial at any institution.
- Minimum of 4 weeks from last dose of investigational agent
- Prior exposure to PD-1 or CTLA4 antibodies in the post-allogeneic transplant setting. Participants who received such agents pre-allogeneic transplant will NOT be excluded.
- Prior exposure to daratumumab in the post-allogeneic transplant setting within two months of start date of treatment with this investigational protocol. Participants who received this agent pre-allogeneic transplant will NOT be excluded
- Concurrent therapies targeted at disease relapse. However, previous treatments for relapsed disease are allowed.
- Concurrent active malignancy (exceptions: treated solid malignancy in >2 years' remission, treated basal or squamous cell carcinomas of the skin)
- History of Crohn's disease or ulcerative colitis
- History of demyelinating disorder
- Prior intolerance or allergy to tocilizumab
Trial locations and contacts
1 site in 1 country.
United States1 site
Froedtert Hospital and the Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
About this study
Official title: Phase 1 Study of Nivolumab in Combination With Tocilizumab for Treatment of Patients With Relapsed Hematological Malignancies Post-allogeneic Transplant
This is a phase 1, interventional single arm, open label, treatment study designed to evaluate the safety combination programmed cell death protein 1 (PD-1) and interleukin 6 (IL-6) inhibition in participants with relapsed disease post-allogeneic transplant.
Read the detailed description
Study disease: Hematologic malignancies including, but not exclusive to,acute/chronic leukemia, lymphoma, and myelodysplastic syndrome that has relapsed after allogeneic transplant.
Study Rationale: Phase 1 Safety/Dose Finding Study: To determine the safety and maximum tolerated dose of Nivolumab in combination with Tocilizumab.
Study Agent Description:
Tocilizumab is a monoclonal antibody and immunosuppressant; specifically, tocilizumab is an IL-6 receptor antagonist.
Nivolumab is a human immunoglobulin G4 (IgG4) monoclonal antibody that binds to the PD-1 receptor of T cells blocking its interaction with PD-L1 and PD-L2, thereby enhancing T-cell proliferation and allowing the immune system to attack the tumor.
Number of Subjects: A maximum of 12 participants will be enrolled on this Phase 1 study.
Duration of Follow-up: Participants will be followed for up to one year post-treatment for survival and response.
Study Design: This is a 3 + 3 design. In a "3 + 3 design," three participants are initially enrolled into a given dose cohort. If there is no dose limiting toxicity (DLT) observed in any of these subjects, the trial proceeds to enroll additional subjects into the next higher dose cohort. If one subject develops a DLT at a specific dose, an additional three subjects are enrolled into that same dose cohort. Development of DLTs in more than one of six subjects in a specific dose cohort suggests that the maximum tolerated dose (MTD) has been exceeded, and further dose escalation is not pursued.
- Conditions
- Acute Leukemia, Chronic Leukemia, Lymphoma, Myelodysplastic Syndromes
- Being tested
- Nivolumab (.25 mg/kg), Tocilizumab, Nivolumab (.5 mg/kg)
- Medical subject headings
- Lymphoma, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nivolumab (.25 mg/kg)Drug
Also called OPDIVO
Participants will receive Nivolumab at one of two dose levels every 2 weeks for 4 treatments.
TocilizumabDrug
Also called ACTEMRA
Participants will receive 2 doses of tocilizumab
Nivolumab (.5 mg/kg)Drug
Also called OPDIVO
Participants will receive Nivolumab at one of two dose levels every 2 weeks for 4 treatments.
| Study group | Role | What they receive |
|---|---|---|
| Nivolumab (0.25 mg/kg) and Tocilizumab | Experimental | Participant will receive tocilizumab 8 mg/kg IV (max dose 800 mg) on Day 0. On Day 1 participants will receive nivolumab IV (0.25 mg/kg based on dose escalation design).
Nivolumab will be given every ~2 weeks for up to 4 doses and a second dose of Tocilizumab will be given on ~Day 29 on the same day as Dose # 3 of Nivolumab. Receives: Drug: Nivolumab (.25 mg/kg); Drug: Tocilizumab |
| Nivolumab (0.5 mg/kg) and Tocilizumab | Experimental | Participant will receive tocilizumab 8 mg/kg IV (max dose 800 mg) on Day 0. On Day 1 participants will receive nivolumab IV (0.5 mg/kg based on dose escalation design).
Nivolumab will be given every ~2 weeks for up to 4 doses and a second dose of Tocilizumab will be given on ~Day 29 on the same day as Dose # 3 of Nivolumab. Receives: Drug: Tocilizumab; Drug: Nivolumab (.5 mg/kg) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum-tolerated Dose
Determine the safety and the maximum tolerated dose among two candidate doses of nivolumab in combination with tocilizumab for treatment of relapsed hematological malignancy post-allogeneic transplant. Maximum-tolerated dose is based on the determination of dose-limiting toxicities.
Measured: Up to 4 weeks after last dose of study treatment (approximately 3 months)
Secondary outcomes (6)
Response Rates Based on Imaging
The number of subjects with stable disease as evidenced by imaging (Diagnostic positron emission tomography (PET)-CT scans or CT of the neck, chest, abdomen, and pelvis).
Measured: End of study treatment (approximately 2 months)
Response Rates Based on Pathologic Response
The number of subjects with bone marrow response (achievement of complete response; <5% blasts; stable disease; progressive disease).
Measured: End of study treatment (approximately 2 months)
Overall Survival
The number of participants alive.
Measured: Up to 1 year from beginning of treatment
Progression-Free Survival
Determine the number of subjects alive and in remission after treatment.
Measured: Up to 1 year from beginning of treatment
Duration of response in responding participants
Number of subjects with complete response or stable disease.
Measured: Up to 1 year from the beginning of treatment
Dose-limiting toxicities
The number of subjects with dose-limiting toxicities. This will be measured by the number of adverse events as defined by the NCI CTCAE version 4.03 non-hematologic ≥ grade 3-5 signs/symptoms or by the development of steroid refractory grade 2-4 graft-versus-host disease or severe chronic graft-versus-host disease.
Measured: Up to 4 weeks after last dose of study treatment (approximately 3 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2018
- Study start14 Sep 2018
- Primary completion15 Jul 2020
- Study completion15 Jul 2020
Why it stopped: Poor accrual and loss of funding.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute LeukemiaStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical College of Wisconsin
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nirav Shah, Medical College of Wisconsin
- Investigators
- Nirav Shah, MD, Principal investigator, Medical College of Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03588936
- Sponsor's protocol ID
- PRO32525
- Status last verified
- Oct 2021
- First submitted
- 4 Jul 2018
- Last updated
- 11 Oct 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study of Nivolumab in Combination With Tocilizumab for Treatment of Patients With Relapsed Hematological Malignancies Post-allogeneic Transplant
- ClinicalTrials.gov ID
- NCT03588936
- Acronym / sponsor ID
- PRO32525
- Conditions
- Acute Leukemia, Chronic Leukemia, Lymphoma, Myelodysplastic Syndromes
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor accrual and loss of funding.
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Medical College of WisconsinUniversity, hospital or other
- Study start
- 14 Sep 2018 (actual)
- Primary completion
- 15 Jul 2020 (actual)
- Study completion
- 15 Jul 2020 (actual)
- First posted
- 17 Jul 2018 (actual)
- Results
- Not posted in the source record
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 1, interventional single arm, open label, treatment study designed to evaluate the safety combination programmed cell death protein 1 (PD-1) and interleukin 6 (IL-6) inhibition in participants with relapsed disease post-allogeneic transplant.
Detailed description
Study disease: Hematologic malignancies including, but not exclusive to,acute/chronic leukemia, lymphoma, and myelodysplastic syndrome that has relapsed after allogeneic transplant.
Study Rationale: Phase 1 Safety/Dose Finding Study: To determine the safety and maximum tolerated dose of Nivolumab in combination with Tocilizumab.
Study Agent Description:
Tocilizumab is a monoclonal antibody and immunosuppressant; specifically, tocilizumab is an IL-6 receptor antagonist.
Nivolumab is a human immunoglobulin G4 (IgG4) monoclonal antibody that binds to the PD-1 receptor of T cells blocking its interaction with PD-L1 and PD-L2, thereby enhancing T-cell proliferation and allowing the immune system to attack the tumor.
Number of Subjects: A maximum of 12 participants will be enrolled on this Phase 1 study.
Duration of Follow-up: Participants will be followed for up to one year post-treatment for survival and response.
Study Design: This is a 3 + 3 design. In a "3 + 3 design," three participants are initially enrolled into a given dose cohort. If there is no dose limiting toxicity (DLT) observed in any of these subjects, the trial proceeds to enroll additional subjects into the next higher dose cohort. If one subject develops a DLT at a specific dose, an additional three subjects are enrolled into that same dose cohort. Development of DLTs in more than one of six subjects in a specific dose cohort suggests that the maximum tolerated dose (MTD) has been exceeded, and further dose escalation is not pursued.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nivolumab (0.25 mg/kg) and Tocilizumab | Experimental | Drug: Nivolumab (.25 mg/kg), Drug: TocilizumabParticipant will receive tocilizumab 8 mg/kg IV (max dose 800 mg) on Day 0. On Day 1 participants will receive nivolumab IV (0.25 mg/kg based on dose escalation design). Nivolumab will be given every ~2 weeks for up to 4 doses and a second dose of Tocilizumab will be given on ~Day 29 on the same day as Dose # 3 of Nivolumab. |
| Nivolumab (0.5 mg/kg) and Tocilizumab | Experimental | Drug: Tocilizumab, Drug: Nivolumab (.5 mg/kg)Participant will receive tocilizumab 8 mg/kg IV (max dose 800 mg) on Day 0. On Day 1 participants will receive nivolumab IV (0.5 mg/kg based on dose escalation design). Nivolumab will be given every ~2 weeks for up to 4 doses and a second dose of Tocilizumab will be given on ~Day 29 on the same day as Dose # 3 of Nivolumab. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Age≥18 years with hematological malignancies who have undergone allogeneic transplant for hematological malignancy and are ≥180 days post-transplant.
- Relapsed disease post-allogeneic transplant defined as follows i. Acute or Chronic Leukemia or myelodysplastic or myeloproliferative disorders or natural killer (NK) cell neoplasms: Bone marrow (BM) with ≥5% disease involvement or peripheral blood evidence of overt relapse ii. Lymphoma: BM evidence of relapsed/persistent disease or PET/CT or CT evidence of persistent/progressive lymphadenopathy consistent with active lymphoma. Active disease defined as nodal lesions ≥ 20 mm in the long axis or extranodal lesions≥10 mm in long and short axis or bone marrow involvement that is biopsy proven
- Karnofsky performance status ≥70 (See Appendix A for details)
- Creatinine Clearance≥60 ml/min
- Adequate hepatic function, defined as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 x upper limit of normal (ULN). Serum bilirubin and alkaline phosphatase ≤3x x ULN, or considered not clinically significant (e.g. Gilbert's or indirect hyperbilirubinemia) or felt to be due to underlying disease.
Key exclusion criteria (17 listed)
- Positive beta-human chorionic gonadotropin (HCG) in female of child-bearing potential
- Cluster of differentiation 3 (CD3) donor chimerism <5% within 4 weeks of starting study treatment
- Prior administration of donor lymphocyte infusion post-allogeneic transplant within the last 6 months of study treatment
- History of or active autoimmune disease, or other syndrome that requires systemic steroids.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab.
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 |
|---|---|---|
| Nivolumab (.25 mg/kg)Also: OPDIVOParticipants will receive Nivolumab at one of two dose levels every 2 weeks for 4 treatments. | Drug | Nivolumab (0.25 mg/kg) and Tocilizumab |
| TocilizumabAlso: ACTEMRAParticipants will receive 2 doses of tocilizumab | Drug | Nivolumab (0.25 mg/kg) and Tocilizumab, Nivolumab (0.5 mg/kg) and Tocilizumab |
| Nivolumab (.5 mg/kg)Also: OPDIVOParticipants will receive Nivolumab at one of two dose levels every 2 weeks for 4 treatments. | Drug | Nivolumab (0.5 mg/kg) and Tocilizumab |
Primary outcome
Maximum-tolerated Dose
Time frame: Up to 4 weeks after last dose of study treatment (approximately 3 months)
Determine the safety and the maximum tolerated dose among two candidate doses of nivolumab in combination with tocilizumab for treatment of relapsed hematological malignancy post-allogeneic transplant. Maximum-tolerated dose is based on the determination of dose-limiting toxicities.
6 secondary outcomes
Response Rates Based on Imaging
Time frame: End of study treatment (approximately 2 months)
Response Rates Based on Pathologic Response
Time frame: End of study treatment (approximately 2 months)
Overall Survival
Time frame: Up to 1 year from beginning of treatment
Progression-Free Survival
Time frame: Up to 1 year from beginning of treatment
Duration of response in responding participants
Time frame: Up to 1 year from the beginning of treatment
Dose-limiting toxicities
Time frame: Up to 4 weeks after last dose of study treatment (approximately 3 months)
Results and safety
The study was stopped early (reason given: Poor accrual and loss of funding.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Oct 2021.
- 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.
Nirav Shah, 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 1 study testing Nivolumab (.25 mg/kg), Tocilizumab and Nivolumab (.5 mg/kg) in people with Acute Leukemia and Chronic Leukemia, 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 11 inclusion and 17 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: stopped early, as of the sponsor's last update on 11 Oct 2021. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Poor accrual and loss of funding.). Results are not available in the source record.
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?
Maximum-tolerated Dose (time frame: Up to 4 weeks after last dose of study treatment (approximately 3 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Oct 2021.