A Phase 1/2 Study of CYT-0851 in B-Cell Malignancies and Advanced Solid Tumors
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT03997968 |
Recruitment Status :
Recruiting
First Posted : June 25, 2019
Last Update Posted : August 26, 2022
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Condition or disease | Intervention/treatment | Phase |
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Malignancy Non-hodgkin Lymphoma Multiple Myeloma Breast Cancer Ovarian Cancer Soft Tissue Sarcoma Head and Neck Cancer DLBCL Mantle Cell Lymphoma Follicular Lymphoma Pancreatic Cancer CLL Small Cell Lung Cancer Squamous Cell Carcinoma of Head and Neck Triple Negative Breast Cancer | Drug: CYT-0851 Drug: CYT-0851 in combination with gemcitabine Drug: CYT-0851 in combination with capecitabine Drug: CYT-0851 in combination with rituximab and bendamustine | Phase 1 Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 320 participants |
Allocation: | Non-Randomized |
Intervention Model: | Sequential Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Multi-Center, Open Label Phase 1/2 Study of CYT-0851 in Patients With Relapsed/Refractory B-Cell Malignancies and Advanced Solid Tumors |
Actual Study Start Date : | October 9, 2019 |
Estimated Primary Completion Date : | February 2023 |
Estimated Study Completion Date : | December 2023 |

Arm | Intervention/treatment |
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Experimental: CYT-0851 dose escalation
Part A: CYT-0851 administered orally in rising doses QD or BID for 28 day cycles
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Drug: CYT-0851
Part A and B: Daily oral doses of CYT-0851 for 28 day cycles |
Experimental: CYT-0851 dose expansion
Part B: CYT-0851 administered orally at the selected Phase 2 dose for 28 day cycles
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Drug: CYT-0851
Part A and B: Daily oral doses of CYT-0851 for 28 day cycles |
Experimental: CYT-0851 and rituximab and bendamustine
Part C: Daily oral doses of CYT-0851 for 28 days in combination with rituximab on Day 1 and bendamustine on Days 1 and 2 of each 28 day cycle
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Drug: CYT-0851
Part A and B: Daily oral doses of CYT-0851 for 28 day cycles Drug: CYT-0851 in combination with rituximab and bendamustine Part C: Daily oral doses of CYT-0851 for 28 days in combination with rituximab and bendamustine |
Experimental: CYT-0851 and gemcitabine
Part D: Daily oral doses of CYT-0851 for 28 days in combination with gemcitabine on Day 1, 8 and 15 of each 28 day cycle
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Drug: CYT-0851
Part A and B: Daily oral doses of CYT-0851 for 28 day cycles Drug: CYT-0851 in combination with gemcitabine Part D: Daily oral doses of CYT-0851 for 28 days in combination with gemcitabine |
Experimental: CYT-0851 and capecitabine
Part E: Daily oral doses of CYT-0851 for 21 days in combination with capecitabine on Days to 14 of each 21 day cycle
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Drug: CYT-0851
Part A and B: Daily oral doses of CYT-0851 for 28 day cycles Drug: CYT-0851 in combination with capecitabine Part E: Daily oral doses of CYT-0851 for 21 days in combination with capecitabine |
- Part A: Incidence of dose limiting toxicity [ Time Frame: 28 Days ]Cycle 1 Dose limiting toxicities and determination of the maximum tolerated dose
- Part B: Objective response rate [ Time Frame: 24 Weeks ]clinical benefit as determined by investigator assessments of tumor response
- Part C: Incidence of dose limiting toxicity [ Time Frame: 28 Days ]Cycle 1 Dose limiting toxicities and determination of the maximum tolerated dose in combination with rituximab and bendamustine
- Part D: Incidence of dose limiting toxicity [ Time Frame: 28 Days ]Cycle 1 Dose limiting toxicities and determination of the maximum tolerated dose in combination with gemcitabine
- Part E: Incidence of dose limiting toxicity [ Time Frame: 21 Days ]Cycle 1 Dose limiting toxicities and determination of the maximum tolerated dose in combination with capecitabine
- Part A: Incidence of adverse events and other safety measures [ Time Frame: 28 Days ]
incidence of adverse events changes in laboratory parameters, vital signs and ECGs
• Establish the PK of CYT-0851 Evaluate the type and frequency of adverse events
- Part C: Incidence of adverse events and other safety measures [ Time Frame: 28 Days ]
incidence of adverse events changes in laboratory parameters, vital signs and ECGs
• Establish the PK of CYT-0851 Evaluate the type and frequency of adverse events
- Part D: Incidence of adverse events and other safety measures [ Time Frame: 28 Days ]
incidence of adverse events changes in laboratory parameters, vital signs and ECGs
• Establish the PK of CYT-0851 Evaluate the type and frequency of adverse events
- Part E: Incidence of adverse events and other safety measures [ Time Frame: 21 Days ]
incidence of adverse events changes in laboratory parameters, vital signs and ECGs
• Establish the PK of CYT-0851 Evaluate the type and frequency of adverse events
- Part A: Assessment of pharmacokinetic parameters [ Time Frame: Phase 1: 12 months ]Summarize PK parameters including Cmax, AUC and tmax
- Part C: Assessment of pharmacokinetic parameters [ Time Frame: Phase 1: 12 months ]Summarize PK parameters including Cmax, AUC and tmax
- Part D: Assessment of pharmacokinetic parameters [ Time Frame: Phase 1: 12 months ]Summarize PK parameters including Cmax, AUC and tmax
- Part E: Assessment of pharmacokinetic parameters [ Time Frame: Phase 1: 12 months ]Summarize PK parameters including Cmax, AUC and tmax
- Part B: Assessment of pharmacokinetic parameters [ Time Frame: Phase 1: 12 months ]Summarize PK parameters including Cmax, AUC and tmax
- Part A: Objective response rate [ Time Frame: 24 months ]clinical activity as assessed by investigator assessment of objective response and duration of response
- Part C: Objective response rate [ Time Frame: 24 months ]clinical activity as assessed by investigator assessment of objective response and duration of response
- Part D: Objective response rate [ Time Frame: 24 months ]clinical activity as assessed by investigator assessment of objective response and duration of response
- Part E: Objective response rate [ Time Frame: 24 months ]clinical activity as assessed by investigator assessment of objective response and duration of response
- Part B: Anti-tumor activity and by DOR [ Time Frame: 24 months ]Antitumor activity as assessed by duration of response
- Part B: Anti-tumor activity by PFS [ Time Frame: 24 months ]Antitumor activity as assessed by progression free survival
- Part B: Anti-tumor activity by DCR [ Time Frame: 24 months ]Antitumor activity as assessed by disease control rate
- Part B: Anti-tumor activity by OS [ Time Frame: 24 months ]Antitumor activity as assessed by overall survival
- Part B: Safety assessment [ Time Frame: 24 months ]Safety as determined by incidence of AEs and SAEs and changes in laboratory, vitals and ECG findings

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Key Phase 1 Inclusion Criteria
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Male or female ≥18 years of age at time of informed consent.
- Female subjects of childbearing potential must be non-lactating, not pregnant as confirmed by a negative serum pregnancy test at most 30 days before enrollment and within 72 hours before the first administration of CYT-0851
- Female subjects of childbearing potential must not donate ova during the study and for at least 90 days after the last dose of study drug and must agree to continue using an effective method of contraception during the screening period to first study drug administration until 90 days after the last dose of study drug
- Male subjects who have not had a vasectomy must agree to use an effective method of contraception during the study and until 90 days after the last dose of the study drug, and to not donate sperm during the study and for at least 90 days after the last dose of study drug
- ECOG Performance Status of 0-1
- Measurable disease defined by disease-specific response criteria
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Histologically-proven B cell malignancies, meeting the following criteria:
- Relapsed, refractory B-cell non-Hodgkin lymphoma requiring therapy, after at least two prior therapies, and if transplanted, then at least 3-month post autologous stem cell transplant and if CART-treated, then evidence of progression no sooner than 3 months post CART treatment, or
- Relapsed, refractory chronic lymphocytic leukemia requiring therapy after at least two prior therapies, including BTK and BCL-2 inhibitor therapy (unless ineligible for such therapy), or
- For multiple myeloma, relapsed or progressive on or after treatment with at least three prior therapies that included a proteasome inhibitor, an imide, daratumumab, and if transplant eligible, a bone marrow transplant (unless unfit for transplant), or
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Histologically-proven solid tumor meeting the following criteria:
- Patients must have failed, refused, or not be eligible for further standard therapies (including chemotherapy, hormonal therapies, Her-2 directed therapies, as appropriate) expected to provide clinical benefit, and meeting the following criteria
- Metastatic breast cancer (including ER/PR positive or negative, Her-2 positive and negative, triple negative), treated with at least 1 prior therapy for metastatic disease, or
- Recurrent squamous cell carcinoma of the head and neck (HNSCC) (dose escalation) or human papilloma virus positive (HPV+) HNSCC (dose-escalation and backfill), treated with at least 1 prior therapy, or
- Ovarian cancer, progressive after treatment with at least prior platinum-based chemotherapy, and therapy with a PARP inhibitor or
- Soft tissue sarcoma, treated with at least one line of prior systemic therapy, or
- Recurrent metastatic or locally advanced pancreatic cancer after first line chemotherapy (backfill or combination patients only) or
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Histologically-proven advanced small-cell lung cancer (SCLC) (monotherapy backfill patients only).
- Patients with mixed histology are not allowed
- Prior treatment with platinum containing chemotherapy regimen with no evidence of progression within 90 days of last dose of platinum agent and anti-PD-(L)1 unless contraindicated
- At least 1 prior line of chemotherapy, but no more than 3 prior lines of therapy
- Understands the procedures and requirements of the study and provides written informed consent and authorization for protected health information disclosure
- Willing and able to comply with the requirements of the study protocol
- Site of disease amenable to a biopsy and willing to undergo biopsy required for backfill, or for dose-escalation if considered unsafe (approval to participate in the study required by the Medical Monitor) provide an archival sample ≤ 12 months old
Key Phase 2 Inclusion Criteria
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Male or female ≥18 years of age at time of informed consent.
- Female subjects of childbearing potential must be non-lactating, not pregnant as confirmed by a negative serum pregnancy test at most 30 days before enrollment and within 72 hours before the first administration of CYT-0851
- Female subjects of childbearing potential must not donate ova during the study and for at least 90 days after the last dose of study drug and must agree to continue using, an effective method of contraception during the screening period to first study drug administration until 90 days after the last dose of study drug
- Male subjects who have not had a vasectomy must agree to use an effective method of contraception during the study and until 90 days after the last dose of the study drug, and to not donate sperm during the study and for at least 90 days after the last dose of study drug
- ECOG Performance Status of 0-1
- Measurable disease defined by disease-specific response criteria
- Site of disease amenable to a biopsy and willing to undergo a biopsy for the determination of biomarker status, or, if considered unsafe (approval to participate in the study required by the Medical Monitor), archival sample ≤ 12 months old for determination of biomarker status.
- Biomarker positive on recent biopsy or bone marrow sample if required for the specific cohort.
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Histologically-proven B cell malignancies, meeting the following criteria:
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DLBCL Cohort
- Histologically-documented DLBCL or double hit lymphoma (B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma with BCL2 and MYC translocations (WHO Classification)
- Progressing on or after treatment with at least two prior lines of therapy, including R-CHOP or equivalent first line therapy
- If transplanted, then at least 3-month post autologous stem cell transplant
- If CART-treated, then evidence of progression no sooner than 3 months post CART treatment
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MCL Cohort
- Histologically-documented MCL
- Any stage at diagnosis
- Progressing on or after treatment with at least 2 prior lines of therapy, including a Bruton tyrosine kinase (BTK) inhibitor, after a 14-day washout period
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Multiple Myeloma Cohort
- Relapsed or progressing after treatment with at least 3 prior therapies that include a proteasome inhibitor, an Immunomodulatory imide drug (IMiD), daratumumab, and, if transplant eligible, a bone marrow transplant (unless unfit for transplant)
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Or Histologically-proven solid tumors meeting the following criterial
- Patients must have failed, refused, or not be eligible for further standard therapies (including chemotherapy, hormonal therapies, Her-2 directed therapies, as appropriate) expected to provide clinical benefit, and meeting the following criteria
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Triple Negative Breast Cancer Cohort
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Histologically-documented triple negative breast cancer, ER/PR negative (defined as <10% of cells expressing hormonal receptors via immunohistochemistry (IHC) analysis), and HER2-negative, defined as either of the following by local laboratory assessment:
- In situ hybridization (ISH) non-amplified (ratio of HER2 to CEP17 < 2.0 or single probe average HER2 gene copy number < 4 signals/cell), or
- IHC 0 or IHC 1+
- At least 1 prior line of chemotherapy, but no more than 5 prior lines of chemotherapy
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Ovarian Cancer Cohort
- Histologically-proven metastatic epithelial ovarian cancer
- Prior treatment with a platinum containing chemotherapy regimen
- At least 1 prior line of therapy, but no more than 5 prior lines of chemotherapy
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Pancreatic Cancer Cohort
- Histologically-proven metastatic or locally advanced pancreatic cancer
- At least 1 prior line of chemotherapy but no more than 4 prior lines of systemic therapy
- Soft Tissue Sarcoma Cohort 1) Histologically-proven advanced soft-tissue sarcoma excluding all types of adipocytic sarcoma and GIST 2) At least 1 prior line of systemic therapy (unless no standard of care exists), but no more than 5 prior lines of systemic therapy
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Follicular Lymphoma Cohort
- Histologically-documented follicular lymphoma
- Relapsed, refractory follicular lymphoma requiring therapy, after at least two prior therapies, and if CART-treated, then evidence of progression no sooner than 3 months post CART treatment
- Understands the procedures and requirements of the study and provides written informed consent and authorization for protected health information disclosure
- Willing and able to comply with the requirements of the study protocol
Key Exclusion Criteria
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Medical Conditions
- Known history of HIV
- Known history of viral hepatitis B unless HBV viral load is below the limit of quantification and off viral suppressive therapy
- Know history of hepatitis C unless antiviral treatment with curative intent completed and HCV viral load is below the limit of quantification.
- Myocardial infarction or stroke within 6 months
- Uncontrolled hypertension (systolic blood pressure (SBP) > 160 or diastolic blood pressure (DBP) >100 on maximal medical therapy)
- History of interstitial pulmonary disease
- Unresolved pneumonitis
- Grade ≥ 3 neuropathy
- Known active central nervous system (CNS) metastases. Subjects with previously treated CNS metastases may participate as long as clinically and radiologically stable for at least 4 weeks after treatment, have no evidence of new or enlarging lesions and are off steroids and asymptomatic for 28 days prior to dosing with study medication
- Known history of meningeal involvement or meningeal carcinomatosis
- Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for > 2 weeks prior to screening visit
- Presence of clinically significant cataracts
- Second malignancy, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, or other malignancy that is in remission or stable and for which patients have not been on active anti-cancer therapy for 2 years
- Pregnant or lactating. If β-HCG is elevated, eligible if ultrasound confirms absence of a pregnancy.
- Dementia or significantly altered metal status
- Bowel obstruction requiring medical management less than 4 weeks prior to screening
- Inability to tolerate oral intake that includes 2 full meals per day (or equivalent) or swallow pills.
- Recurrent ascites requiring paracentesis more frequently than every 4 weeks or within 14 days of screening.
- Weight loss of more than 10% over the preceding 3 months prior to screening
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Prior/Concomitant Therapy
- Prior allogeneic stem cell transplant
- On systemic antibiotic, antifungal or anti-viral therapy
- White blood cell (WBC) growth factors administered within 14 days of screening visit
- Cancer therapy within 14 days prior to treatment with study drug
- On narrow therapeutic index medications that are sensitive substrates of CYP3A, P-gp or BCRP (or caution is warranted with approval by the Sponsor).
- On any drug known to prolong QTc interval (eg, certain antiarrhythmic, antimicrobials) that cannot be discontinued or interrupted 72 hours before the Day 1 dose through Day 2, and 72 hours before the Day 15 dose until Day 16 (BID dosing) or the Day 22 dose until Day 23 (QD dosing), in Cycle 1 (see Section 7.6.1 for a list of drugs).
- On systemic corticosteroid treatment for non-tumor indication at a daily dose equivalent to >10mg of Prednisone
- Prior/Concurrent Clinical Study Experience a. Participation in another clinical trial (unless in the observation phase, or an observational study), or exposure to any investigational agent within 14 days prior to treatment with study drug
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Laboratory assessments
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Complete blood count (CBC):
Monotherapy and Chemotherapy Combinations 1 and 2:
- ANC < 1.0 × 10^9/L
- PLT < 75 × 10^9/L
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Hgb < 9.0 g/dL
Chemotherapy Combination Group 3:
1) ANC < 1.5 × 10^9/L 2) PLT < 100 × 10^9/L 3) Hgb < 9.0 g/dL
Monotherapy and Chemotherapy Combination Groups 1 and 2:
- Calculated Creatinine clearance (Cockcroft-Gault) < 40 mL/min
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Chemotherapy Combination Group 3:
b. Calculated Creatinine clearance (Cockcroft-Gault) < 50 mL/min c. Hepatic function
- AST > 2.0 × ULN
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ALT > 2.0 × ULN d. Total bilirubin > 1.5 x ULN e. Albumin < 2.8 g/dL 5. ECG Exclusion a. Screening QTc interval > 450 milliseconds for males and QTc > 470 ms for females (corrected by Fridericia) 6. Other Exclusions
- Unwilling or unable to make all planned study visits
- Unwilling or unable to provide a recent biopsy or bone marrow sample prior to enrollment and during study; Note: certain exceptions may be permitted allowing archival specimens prior to treatment or for subjects where a specimen is not required for biomarker positive testing
- Significant medical diseases or conditions, as assessed by the Investigators and Cyteir that would substantially increase the risk-benefit ratio of participating in the study. This includes but is not limited to acute myocardial infarction, arterial thrombosis, significant gastrointestinal bleed, or unstable angina within the last 6 months uncontrolled diabetes mellitus, current active infections, severely immunocompromised state, and congestive heart failure New York Heart Association (NYHA) Class III-IV, left ventricular ejection fraction (LVEF) < 40% d: Chemotherapy Combination Group 3 only: known history of dhydropyrimidine dehydrogenase deficiency

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03997968
Contact: Judson Englert, MD | 857-285-4140 | clinicaltrials@cyteir.com | |
Contact: Susan Doleman | 857-285-4140 | clinicaloperations@cyteir.com |
United States, California | |
University of California San Francisco | Recruiting |
San Francisco, California, United States, 94158 | |
Contact: Lauren Wilch 415-353-3642 Lauren.Wilch@ucsf.edu | |
Principal Investigator: Pamela Munster, MD | |
Stanford Comprehensive Cancer Center | Recruiting |
Stanford, California, United States, 94305 | |
Contact: Mariel Rojas 650-723-0530 mlrojas@stanford.edu | |
Principal Investigator: Ranjana Advani, MD | |
United States, Colorado | |
Sarah Cannon Research Institute at HealthONE | Recruiting |
Denver, Colorado, United States, 80218 | |
Contact: Susan Hall 720-754-2610 Susan.Hall3@sarahcannon.com | |
Principal Investigator: Gerald Falchook, MD | |
United States, Florida | |
Florida Cancer Specialists and Research Institute | Recruiting |
Sarasota, Florida, United States, 34232 | |
Contact: Karolyn Simpson, RN 941-377-9993 KaSimpson@flcancer.com | |
Principal Investigator: Manesh R Patel, MD | |
United States, Massachusetts | |
Massachusetts General Hospital | Recruiting |
Boston, Massachusetts, United States, 02114 | |
Contact: Dejan Juric, MD 617-724-4000 djuric@partners.org | |
Principal Investigator: Dejan Juric, MD | |
Dana Farber Cancer Institute | Recruiting |
Boston, Massachusetts, United States, 02115 | |
Contact 877-338-7425 | |
Principal Investigator: Geoffrey I. Shapiro, MD | |
United States, Michigan | |
University of Michigan | Recruiting |
Ann Arbor, Michigan, United States, 48109 | |
Contact: Monica Burness, MD 734-232-0759 mburness@med.umich.edu | |
Principal Investigator: Monica Burness, MD | |
United States, Minnesota | |
Mayo Clinic | Recruiting |
Rochester, Minnesota, United States, 55905 | |
Contact: Clinical Trials Referral Office 855-776-0015 | |
Principal Investigator: Grzegorz S Nowakowski, MD | |
United States, New Jersey | |
John Theurer Cancer Center at HUMC | Recruiting |
Hackensack, New Jersey, United States, 07601 | |
Contact: Chelsea McCabe 551-996-4725 chelsea.mccabe@hackensackmeridian.org | |
Principal Investigator: David Siegel, MD | |
United States, New York | |
NYU Langone Health | Recruiting |
New York, New York, United States, 10016 | |
Contact: Nina Beri, MD 212-731-5770 Nina.Beri@nyulangone.org | |
Principal Investigator: Nina Beri, MD | |
United States, Oklahoma | |
Oklahoma University-Stephenson Cancer Center | Recruiting |
Oklahoma City, Oklahoma, United States, 73104 | |
Contact 405-271-8778 PhaseI-Referrals@ouhsc.edu | |
Principal Investigator: Kathleen Moore, MD | |
United States, Pennsylvania | |
Thomas Jefferson University, Sidney Kimmel Cancer Center | Recruiting |
Philadelphia, Pennsylvania, United States, 19107 | |
Contact: Dennis Stone 215-955-6407 Dennis.Stone@Jefferson.edu | |
Principal Investigator: Neil Palmisiano, MD | |
Sub-Investigator: Gina Keiffer, MD | |
United States, Tennessee | |
Sarah Cannon Research Institute at Tennessee Oncology | Recruiting |
Nashville, Tennessee, United States, 37203 | |
Contact: Davinia McComb, RN, OCN 615-815-9963 | |
Principal Investigator: David Spigel, MD | |
United States, Texas | |
The University of Texas MD Anderson Cancer Center | Recruiting |
Houston, Texas, United States, 77030 | |
Contact: Sarah Travasos 713-563-4431 sktravasos@mdanderson.org | |
Principal Investigator: Timothy A Yap, MD, PhD | |
United States, Washington | |
University of Washington Seattle Cancer Center | Recruiting |
Seattle, Washington, United States, 98109 | |
Contact: Harini Ramachandran 206-606-6448 harinir@seattlecca.org | |
Principal Investigator: Ryan Lynch, MD | |
United States, Wisconsin | |
Medical College of Wisconsin | Recruiting |
Milwaukee, Wisconsin, United States, 53226 | |
Contact: Michael Jacklin 414-804-8839 mjacklin@mcw.com | |
Principal Investigator: Mehdi Hamadani, MD |
Study Director: | Judson Englert, MD | Cyteir Therapeutics |
Responsible Party: | Cyteir Therapeutics, Inc. |
ClinicalTrials.gov Identifier: | NCT03997968 |
Other Study ID Numbers: |
CYT-0851-01 |
First Posted: | June 25, 2019 Key Record Dates |
Last Update Posted: | August 26, 2022 |
Last Verified: | December 2021 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Oral MCT-inhibitor; refractory; B-cell; solid tumor cancer |
Lymphoma Breast Neoplasms Multiple Myeloma Neoplasms Sarcoma Lymphoma, Mantle-Cell Small Cell Lung Carcinoma Triple Negative Breast Neoplasms Squamous Cell Carcinoma of Head and Neck Neoplasms by Histologic Type Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Neoplasms by Site |
Breast Diseases Skin Diseases Carcinoma, Squamous Cell Carcinoma Neoplasms, Glandular and Epithelial Neoplasms, Plasma Cell Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoma, Non-Hodgkin Neoplasms, Connective and Soft Tissue |