Phase 1b/2 Clinical Study of the Safety, Tolerability, and Pharmacokinetic and Pharmacodynamic Profiles of CFI-400945 as a Single Agent or in Combination With Azacitidine or Decitabine in Patients With AML, MDS or CMML TWT-202

What's the purpose of this trial?

The purpose of this study is to test the safety of an investigational drug called CFI-400945 alone and in combination with azacitidine or decitabine

This trial is currently open and accepting patients.

What will happen during the trial?

You may be able to join this trial if you:

The following criteria is a partial list of reasons why patients may be eligible to participate in this clinical trial. Further evaluation with a medical professional is required.

Inclusion Criteria:

1. Patients must be \>18 years of age
2. For Parts 1A and 1B, the following malignancy types will be included:

1. Relapsed or refractory AML.
2. MDS, after prior hypomethylating agents.
3. CMML, with progressive disease/lack of response after hypomethylating agents

For Parts 1A and 1B, Patients may have relapsed or refractory disease.
3. For Parts 2A and 2B, the following malignancy types will be included:

1. Relapsed or Refractory AML.
2. MDS patients should be limited to high risk disease
3. MDS or CMML should be previously untreated and patients with AML may have relapsed or refractory disease;
4. Have clinically acceptable laboratory screening results (i.e., clinical chemistry, hematology, and urinalysis) within certain limits per protocol.
5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Exclusion Criteria:

1. Patients who have received investigational therapy, radiotherapy, immunotherapy, monoclonal antibodies, or chemotherapy within 14 days or 5 half-lives (whichever is shorter)
2. Allogeneic or autologous transplant for AML with infusion of stem cells within 90 days before Cycle 1 Day 1, or on active immunosuppressive therapy for graft-versus-host disease (GVHD) or GVHD prophylaxis within 2 weeks of Cycle 1 Day 1.
3. Any Grade ≥ 2 persistent non-hematological toxicity related to allogeneic transplant, such as those requiring systemic immunosuppressive therapy.

Additional Trial Information

Phase 1/2

Enrollment: 72 patients (estimated)

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Published Results

Preliminary Results from a Phase 2 Open-Label, Multicenter, Dose Optimization Clinical Study of the Safety, Tolerability, and Pharmacokinetic (PK) and Pharmacodynamic (PD) Profiles of Cfi-400945 As a Single Agent or in Combination with Azacitidine or Decitabine in Patients with Acute Myeloid Leukemia, Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia (TWT-202)

November 15, 2022

As of the 30Jun22 data cut off, 9 pts had been enrolled into the study. Four (44%) pts had AML, 2 (22%) had MDS, 3 (33%) had CMML. The median number of prior therapies was 2 (range 1-4), and 2 (22%) pts had received a stem cell transplant. Six (66%) were male and the median age was 69 (range 22-75). Three of 4 AML pts had unfavorable risk cytogenetics by ELN 2017 criteria, and 2 pts (1 each with MDS, CMML) with TP53 mutations. Five pts received 32mg and 4 pts 48mg. There have been no DLTs. There have been 8 (89%) SAEs with the following occurring in >2 pts (febrile neutropenia (6 pts), pneumonia (2 pts)). Common treatment emergent adverse events (TEAE) in > 2 pts were febrile neutropenia 6 pts (67%), hypokalemia 5pts (56%), anemia and hypomagnesemia 4 pts each (44%), hypophosphatemia, diarrhea, abdominal pain, nausea, vomiting, dyspnea, peripheral edema 3 pts each (33%). Thirty-three percent (20 events, 3 pts) of the grade 3 or greater TEAE's were considered related to CFI-400945. There have been no CR or PR per ELN response criteria observed to date, however, there were 2 (50%) SD per IWG criteria at the 48 mg dose level (1-MDS, 1-CMML). Pharmacokinetic (PK) evaluations indicated that the mean terminal-life ranged from 7 - 10 hours. Low accumulation was observed after 21 days of daily dosing (AR <2-fold). In general, exposure in this study is overlapped with that observed in the PMCC study. PD studies evaluating the effect of CFI-400945 on markers of mitosis, ploidy, and centriole function are ongoing.

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Trial Locations

All Trial Locations

View all clinical trial locations sorted by state.

California

City of Hope Comprehensive Cancer Center Beckman Research Institute

Duarte, CA

Open and Accepting

University of California Davis Comprehensive Cancer Center

Sacramento, CA

Open and Accepting

New York

Weill Cornell

New York, NY

Open and Accepting

Ohio

Ohio State University Comprehensive Cancer Center James Cancer Hospital and Solove Research Institute

Columbus, OH

Open and Accepting

Texas

MD Anderson Cancer Center The University of Texas

Houston, TX

Open and Accepting
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