Acute Myeloid Leukemia, Diffuse Large B-Cell Lymphoma, Lymphoma, Multiple Myeloma
Conditions
Keywords
Neoplasms, Lymphoma, Myeloma, Leukemia
Brief summary
The purpose of this clinical trial is to learn how the experimental medicine maplirpacept (PF-07901801) affects people with various types of blood cancers: * relapsed or refractory (R/R) lymphoma * multiple myeloma * newly diagnosed acute myeloid leukemia (AML). This trial will be conducted in the outpatient setting in 2 parts, phase 1a and phase 1b. You may only participate in one part of the study. During phase 1a of this study, we will explore how much maplirpacept (PF-07901801), when used by itself, can be safely used. If you have lymphoma, the study medicine maplirpacept (PF-07901801) will be given by infusion through a vein once a week or once every 2 weeks or every 3 weeks as determined by your doctor. Following your first dose, you will be expected to come back twice more the first week. From week 2, you will have weekly visits for blood tests, questions about your medications, any side effects, or illnesses you may have experienced and your cancer response. After you have completed 21 days (for every week dosing) or 42 days (for every 2- or 3-weeks dosing), your doctor will discuss whether you should stop study treatment or continue. If you continue, you will be expected to come back weekly for blood tests, vital signs, a brief physical exam, asked about any side effects or illnesses you may have experienced and medications you may be taking. The dosing schedule you are assigned to will continue until your disease has worsened, significant side effects occur or other reasons that lead you and your doctor to decide treatment may be stopped. To be eligible for the first part of the study you must be 18 years or older, your disease has worsened after receiving other medicines approved for blood cancer, no other treatment options exist for you, a sample of your tissue for exploratory research which can be taken from tissue already obtained or if necessary, a new sample of your tissue will be taken so your disease may be seen and measured on routine tests/scans. If you have had radiation therapy or received any anticancer medication within 14 days before the planned start of study treatment your doctor will let you know if you are eligible to participate in the study. If you have had major surgery within 30 days before the planned start of study treatment you may not be eligible to participate. The phase 1a part of the study may last up to 51/2 years. How long you participate in this study depends on side effects you may have to the study drug. It also depends on how your cancer responds to the study drug. Therefore, you may remain in the study as long as you and your study doctor think you may benefit. However, you are free to stop taking part in this study at any time and for any reason. During phase 1b part of this study, we will explore how much maplirpacept (PF-07901801), when used with other anticancer medicine(s), can be safe and reduce cancer growth. In the phase 1b part of this study, you will receive maplirpacept (PF-07901801) and other anticancer medicine(s). Which medicine combination you will receive depends on the types of cancer under treatment. Your treatment experiences will be examined to determine if maplirpacept (PF-07901801) when given with other anticancer medicine(s), is safe and can reduce cancer growth. To be eligible for the second part of the study you may have newly diagnosed Acute Myelocytic Leukemia with or without a genetic mutation or you have Multiple Myeloma or Diffuse Large B Cell Lymphoma, and your disease has worsened. The Phase 1b part of this study may last as long as you and your study doctor think you may benefit which could be up to approximately 31/2 years. How long you participate in this study depends on side effects you may have to the study drug. It also depends on how your cancer responds to the study drug. Therefore, you may remain in the study as long as you and your study doctor think you may benefit. However, you are free to stop taking part in this study at any time and for any reason.
Detailed description
This is a trial of maplirpacept (PF-07901801) in subjects with relapsed or refractory lymphoma or multiple myeloma (MM) and subjects with newly diagnosed acute myeloid leukemia (AML). This trial will be conducted in 2 phases: Phase 1a (Dose-Escalation Phase for Single-Agent maplirpacept (PF-07901801) and Phase 1b maplirpacept (PF-07901801) Combinations and Single-Agent. In the Dose-Escalation Phase for Single-Agent maplirpacept (PF-07901801), subjects with relapsed or refractory lymphoma will be enrolled in sequential dose cohorts. In the Combination and Single-Agent Treatment part, subjects will be included in 1 of 14 cohorts: (Cohort A1 and A2) subjects with newly diagnosed TP53-mutated AML will be treated with maplirpacept (PF-07901801) + azacitidine; (Cohort B1 and B2) elderly subjects or subjects unfit for intensive induction chemotherapies with newly diagnosed TP53-wildtype AML will be treated with maplirpacept (PF-07901801) + azacitidine and venetoclax; (Cohort C1, C2, and C3) subjects with relapsed or refractory MM will be treated with maplirpacept (PF-07901801) + carfilzomib and dexamethasone;(Cohort D1 and D2) subjects in relapsed or refractory CD20+ diffuse large B-cell lymphoma will be treated with maplirpacept (PF-07901801) + an anti-CD20 targeting agent; (Cohort E1 and E2) subjects with relapsed refractory MM will be treated with single-agent maplirpacept (PF-07901801); and (Cohorts F1, F2 and F3) with relapsing or refractory MM will be treated with increasing doses of maplirpacept (PF-07901801) + isatuximab, carfilzomib and dexamethasone.
Interventions
maplirpacept (PF-07901801) will be administered by intravenous infusion at ranging doses, as determined from sequential dosing cohorts.
DRUGAzacitidine
intravenous (IV) or subcutaneous (SC) daily for 7 days, repeated every 4 weeks
DRUGVenetoclax
orally daily for each day of each cycle (first 7 doses taken in clinic). The ramp-up and target dose of venetoclax will be adjusted per the package insert in subjects who are taking concomitant moderate or strong CYP3A4 inhibitors or posaconazole
DRUGCarfilzomib
Days 1, 8, and 15 of 28-day cycles; starting dose IV given on Cycle (C) 1 Day (D) 1, and if tolerated, then increased dose via IV given starting on C1D8 and subsequent doses thereafter.
DRUGDexamethasone
starting dose via IV on Days 1, 8, 15, and increased dose via IV on 28-day cycles
DRUGAnti-CD20 Targeting agent
Days 1,8,15, and 22 of the first 28-day cycle and then on Day 1 of subsequent 21-day cycles. The anti-CD20 targeting agent will be administered for a total of eight doses, and then Cohort F1, F2 and F3: TTI-622 + isatuximab, carfilzomib and dexamethasone Cohort C1, C2 and C3: TTI-622 + Carfilzomib and Dexamethasone will be continued as single-agent therapy.
DRUGIsatuximab
F1: IV dose C0D1, C0D8, C0D15 and C0D22 (lead in phase);weekly during Cycle 1; Cycle 2 and beyond will be administered on Days 1 and 15 (Q2W). F2 and F3: IV dose C0D1 and C0D8 (lead in phase); C1D1, C1D8, C1D15 and C1D22; Cycle 2 and beyond will be administered on days 1 and 15 (Q2W). Carfilzomib: IV dose on days 1 and 2 of cycle 1; then increased IV dose on days 8, 9, 15, and 16 of cycle 1; cycle 2 and beyond: increased IV dose on days 1, 2, 8, 9, 15, and 16. Dexamethasone IV or PO on days 1, 2, 8, 9, 15, 16, 22, and 23 starting cycle 1.
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria (Phase 1a and Phase 1b, all Cohorts): 1. Available fresh or archived tumor tissue. 2. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2. 3. Adequate coagulation function. 4. Adequate hepatic function. 5. Adequate hematologic status. 6. Adequate renal function. 7. Recovery from non-hematopoietic toxicities of previous anticancer drugs or radiotherapy or previous surgeries to ≤Grade 1 (or to baseline grade if condition was pre-existing). Key Inclusion Criteria (Phase 1a): Histologically confirmed relapsed/refractory, transfusion- independent lymphoma (Hodgkin or non-Hodgkin) per the 2014 Lugano classification. Key Inclusion Criteria (Phase 1b Cohort A1 and A2): Histologically confirmed, newly diagnosed TP53-mutated Acute Myeloid Leukemia (AML). Key Inclusion Criteria (Phase 1b Cohort B1 and B2): Histologically confirmed, newly diagnosed TP53-wildtype AML, elderly or unfit for more aggressive treatment. Key Inclusion Criteria (Phase 1b Cohorts C1, C2, C3 and E1, E2, F1, F2, F3): Histologically documented relapsed/refractory Multiple Myeloma (MM). Key Inclusion Criteria (Phase 1b Cohort D1 and D2): Pathologically confirmed relapsed/refractory diffuse large B-cell lymphoma (DLBCL) Key
Exclusion criteria
(Phase 1a and Phase 1b, all Cohorts): 1. Known, current central nervous system disease involvement. 2. Use of any investigational agent or any anticancer drug within 14 days before planned start of study treatment (within 4 weeks for antibody-based therapies and within 8 weeks for cell-based therapies). 3. Subjects who have undergone radiation therapy within 14 days of study treatment administration. 4. Hematopoietic stem cell transplant within 90 days before the planned start of study treatment or subjects with active graft-vs-host disease, with the exception of Grade 1 skin involvement. 5. Major surgery within 30 days before planned start of study treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1a: Number of adverse events (AE) by severity | Through study completion, up to 18 months | To characterize the safety profile (incidence of AEs) |
| Phase 1a: Number of AEs by Frequency | Through study completion, up to 18 months | To characterize the safety profile (incidence of AEs) and |
| Phase 1a: Number of participants with Dose-Limiting Toxicities (DLT) | Up to 21-42 days | To characterize the dose limiting toxicities (DLTs) of TTI-622. |
| Phase 1b: Number of adverse events (AE) by severity | Through study completion, up to 30 months | To characterize the safety profile (incidence of AEs) of TTI-622 given in combinations or as a single agent. |
| Phase 1b: Number of adverse events (AE) by frequency | Through study completion, up to 30 months | To characterize the safety profile (incidence of AEs) of TTI-622 given in combination or as a single agent. |
| Phase 1b: Number of participants with disease response | Through study completion, up to 30 months | To evaluate response rate of each combination treatment in the (7) combination cohorts (A1,A2, B1, B2, C1, C2, C3, D1, D2, F1, F2, F3) and for single agent treatment (Cohort E1 and E2). For AML, response = CR. For MM, response = CR+sCR+VGBR+PR. For DLBCL, OR=CR+PR |
| Phase 1a: Maximum Tolerated Dose (MTD) | Baseline (the start of each sequentially increased treatment dose), up to the 3rd evaluable patient completes DLT observation period of 21 or 42 days. | To characterize the highest dose level for which no more than 1 participant in a dose cohort experienced DLTs. |
| Phase 1b: Recommended dose of TTI-622 in combination with selected anticancer treatments | Through study completion, up to 30 months | To characterize the recommended dose of TTI-622 in combination with selected anticancer treatments in 5 patient populations: * TTI-622 plus azacitidine in newly diagnosed TP53-mutated AML * TTI-622 plus azacitidine and venetoclax in elderly (\>/= 75 years old) or unfit, newly diagnosed TP53-wildtype AML * TTI-622 plus Carfilzomib and dexamethasone in Carfilzomib-refractory, Relapsed/Refractory (R/R) multiple myeloma (MM) after 3 or more prior lines of therapy * TTI-622 plus an anti-CD20 targeting agent (such as ruxience or rituxan) in R/R CD20+ DLBCL after 1 or more prior lines of therapy * TTI-622 plus isatuximab, carfilzomib and dexamethasone in R/R MM after 1-3 prior lines of therapy |
| Phase 1b: Recommended dose of TTI-622 as a single agent | Through study completion, up to 30 months | To characterize the recommended dose of TTI-622 as a single agent in patients with R/R MM after 3 or more prior lines of therapy. |
| Number of participants with response assessments that show preliminary efficacy | Through study completion, up to 30 months | To evaluate preliminary efficacy of each combination treatment in the selected patient populations and for single-agent treatment in R/R MM |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1b: Number of participants with disease control rate (DCR) | Through study completion, up to 30 months | To determine the disease control rate (DCR) for participants treated with TTI-622 when combined with selected anticancer treatments or as a single agent. |
| Phase 1b: Time to response (TTR) | Through study completion, up to 30 months | To determine the time to response (TTR) for participants treated with TTI-622 when combined with selected anticancer treatments or as a single agent. |
| Phase 1b: Event-free survival (EFS) | Through study completion, up to 30 months | To determine event-free survival (EFS; for Cohorts A and B) time for participants treated with TTI-622 when combined with selected anticancer treatments or as a single agent. |
| Phase 1a: Progression free survival (PFS) | Through study completion, up to 18 months | To determine the progression free survival (PFS) time for participants treated with TTI-622. |
| Phase 1b: Progression-free survival (PFS) | Through study completion, up to 30 months | To determine the progression-free survival (PFS) time for participants treated with TTI-622 when combined with selected anticancer treatments or as a single agent. |
| Phase 1b: Number of Participants With Minimal Residual Disease Burden (MRD) Positive, Negative and Not Evaluable (NE) Status | Through study completion, up to 30 months | To determine minimal residual disease (MRD; for Cohorts A, B, C , E and F) for participants treated with TTI-622 when combined with selected anticancer treatments or as a single agent. |
| Phase 1b: Duration of response (DR) | Through study completion, up to 30 months | To determine the duration of response (DOR) for participants treated with TTI-622 when combined with selected anticancer treatments or as a single agent. |
| Phase 1a: TTI-622 PK parameter AUC0-t | Through study completion, up to 18 months | To characterize AUC0-t of TTI-622. |
| Phase 1a: TTI-622 PK parameter Cmax | Through study completion, up to 18 months | To characterize Cmax of TTI-622. |
| Phase 1a: Incidence of anti-drug antibodies (ADA) | Through study completion, up to 18 months | To characterize the immunogenicity of TTI-622. |
| Phase 1a: Number of participants with overall response rate (ORR) for participants treated with TTI-622. | Through study completion, up to 18 months | To determine the disease response. |
| Phase 1a: Number of participants with disease control rate (DCR) | Through study completion, up to 18 months | To determine the disease control rate (DCR) for participants treated with TTI-622. |
| Phase 1a: Time to response (TTR) | Through study completion, up to 18 months | To determine the time to response (TTR) for participants treated with TTI-622. |
| Phase 1a: Duration of Response (DR) | Through study completion, up to 18 months | To determine the duration of response (DR) for participants treated with TTI-622. |
| Phase 1b: TTI-622 PK parameter Cmax when combined with selected anticancer treatments or as a single agent | Through study completion, up to 30 months | To characterize Cmax of TTI-622 when combined with selected anticancer treatments or as a single agent. |
| Phase 1b: incidence of anti-drug antibodies (ADA) Immunogenicity of TTI-622 when combined with selected anticancer treatments or as a single agent | Through study completion, up to 30 months | To characterize the immunogenicity of TTI-622 when combined with selected anticancer treatments or as a single agent |
Countries
United States
Outcome results
None listed