A Clinical Trial to Learn About the Study Medicine (Called TTI-622) Alone and When Used in Combination With Other Medicines to Treat Participants With Advanced Hematological Malignancies, Including Lymphoma, Leukemia and Multiple Myeloma (MM)

Study Purpose

The purpose of this clinical trial is to learn how the experimental medicine (TTI-622) 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 TTI-622, when used by itself, can be safely used. If you have lymphoma, the study medicine TTI-622 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 TTI-622, 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 TTI-622 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 TTI-622, 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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion 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.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03530683
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Pfizer
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Pfizer CT.gov Call Center
Principal Investigator Affiliation Pfizer
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry, Other
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Lymphoma, Multiple Myeloma, Acute Myeloid Leukemia, Diffuse Large B-Cell Lymphoma
Study Website: View Trial Website
Additional Details

This is a trial of TTI-622 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 TTI-622) and Phase 1b (TTI-622 Combinations and Single-Agent). In the Dose-Escalation Phase for Single-Agent TTI-622, 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 TTI-622 + azacitidine; (Cohort B1 and B2) elderly subjects or subjects unfit for intensive induction chemotherapies with newly diagnosed TP53-wildtype AML will be treated with TTI-622 + azacitidine and venetoclax; (Cohort C1, C2, and C3) subjects with relapsed or refractory MM will be treated with TTI-622 + carfilzomib and dexamethasone; (Cohort D1 and D2) subjects in relapsed or refractory CD20+ diffuse large B-cell lymphoma will be treated with TTI-622 + an anti-CD20 targeting agent; (Cohort E1 and E2) subjects with relapsed refractory MM will be treated with single-agent TTI-622; and (Cohorts F1, F2 and F3) with relapsing or refractory MM will be treated with increasing doses of TTI-622 + isatuximab, carfilzomib and dexamethasone.

Arms & Interventions

Arms

Experimental: TTI-622 Monotherapy

In the phase 1a dose- escalation part for single-agent TTI-622, participants with Relapsing or Refractory (R/R) lymphoma will be enrolled in sequential dose cohorts to receive TTI-622 QW to characterize safety, tolerability, and PK; to determine the Maximum Tolerated Dose (MTD) or P1b Starting Dose (a dose lower than or equal to the single-agent MTD), and to gain preliminary evidence of antitumor activity. In addition, participants with R/R Lymphoma may also be enrolled in a cohort to receive TTI-622 Q2W and a cohort to receive TTI-622 Q3W to characterize safety, tolerability, and PK; to determine the MTD; and to gain preliminary evidence of antitumor activity.

Experimental: Cohort A: TTI-622 + Azacitidine

Cohort A1: participants with newly diagnosed TP53-mutated Acute Myelocytic Leukemia (AML) will be treated with TTI-622 QW + azacitidine. Cohort A2: participants with newly diagnosed TP53-mutated AML will be treated with TTI-622 QW + azacitidine.

Experimental: Cohort B: TTI-622 + Azacitidine and Venetoclax

Cohort B1: elderly or unfit participants with newly diagnosed TP53-wildtype AML will be treated with TTI-622 QW + azacitidine and venetoclax Cohort B2: elderly or unfit participants with newly diagnosed TP53-wildtype AML will be treated with TTI-622 QW + azacitidine and venetoclax.

Experimental: Cohort C1, C2 and C3: TTI-622 + Carfilzomib and Dexamethasone

Cohort C1: participants with Relapsing or Refractory (R/R) Multiple Myeloma (MM) will be treated with TTI-622 QW + carfilzomib and dexamethasone. Cohort C2: participants with R/R MM will be treated with TTI-622 QW + carfilzomib and dexamethasone. Cohort C3: participants with R/R MM will be treated with TTI-622 Q2W + carfilzomib and dexamethasone.

Experimental: Cohort D1 and D2: TTI-622 + an anti-CD20 targeting agent

Cohort D1: participants with Relapsing or Recurrent (R/R) CD20+ Diffuse Large B Cell Lymphoma (DLBCL) will be treated with TTI-622 QW, then an increased dose Q3W + an anti-CD20 targeting agent. Cohort D2: participants with R/R CD20+ DLBCL will be treated with TTI-622 dosed QW for 4 weeks, then an increased dose Q3W + an anti-CD20 targeting agent.

Experimental: Cohort E1 and E2: single-agent TTI-622

Cohort E1: participants with Relapsing or Recurrent (R/R) Multiple Myeloma (MM) will be treated with single-agent TTI-622 QW. Cohort E2: participants with R/R MM will be treated with single-agent TTI-622 increased dose QW

Experimental: Cohort F1, F2 and F3: TTI-622 + isatuximab, carfilzomib and dexamethasone

Cohort F1: participants with Relapsing or Recurrent (R/R) Multiple Myeloma (MM) will be treated with increasing doses of TTI-622 + isatuximab, carfilzomib and dexamethasone. Cohort F2: participants with R/R MM will be treated with TTI-622 QW + isatuximab, carfilzomib and dexamethasone. Cohort F3: participants with R/R MM will be treated with TTI-622 increased dose QW + isatuximab, carfilzomib and dexamethasone.

Interventions

Drug: - TTI-622

TTI-622 will be administered by intravenous infusion at ranging doses, as determined from sequential dosing cohorts.

Drug: - Azacitidine

intravenous (IV) or subcutaneous (SC) daily for 7 days, repeated every 4 weeks

Drug: - Venetoclax

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

Drug: - Carfilzomib

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.

Drug: - Dexamethasone

starting dose via IV on Days 1, 8, 15, and increased dose via IV on 28-day cycles

Drug: - Anti-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 TTI-622 will be continued as single-agent therapy.

Drug: - Isatuximab

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.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Keck Hospital of USC, Los Angeles, California

Status

Recruiting

Address

Keck Hospital of USC

Los Angeles, California, 90033

LAC+USC Medical Center, Los Angeles, California

Status

Recruiting

Address

LAC+USC Medical Center

Los Angeles, California, 90033

USC/Norris Comprehensive Cancer Center, Los Angeles, California

Status

Recruiting

Address

USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033

Keck Hospital of USC Pasadena, Pasadena, California

Status

Recruiting

Address

Keck Hospital of USC Pasadena

Pasadena, California, 91105

Keck Medical Center of USC Pasadena, Pasadena, California

Status

Recruiting

Address

Keck Medical Center of USC Pasadena

Pasadena, California, 91105

Colorado Blood Cancer Institute, Denver, Colorado

Status

Recruiting

Address

Colorado Blood Cancer Institute

Denver, Colorado, 80218

Denver, Colorado

Status

Recruiting

Address

HealthONE Presbyterian/St. Luke's Medical Center

Denver, Colorado, 80218

Georgetown University Medical Center, Washington, District of Columbia

Status

Recruiting

Address

Georgetown University Medical Center

Washington, District of Columbia, 20007

Atlanta, Georgia

Status

Not yet recruiting

Address

Blood and Marrow Transplant Group of Georgia

Atlanta, Georgia, 30342

Northside Hospital, Atlanta, Georgia

Status

Not yet recruiting

Address

Northside Hospital

Atlanta, Georgia, 30342

Louisville, Kentucky

Status

Recruiting

Address

Norton Cancer Institute, St Matthews Campus

Louisville, Kentucky, 40207

Louisville, Kentucky

Status

Recruiting

Address

Norton Cancer Institute, St. Matthews Campus, Attn. Becky Champion, PharmD

Louisville, Kentucky, 40207

Louisville, Kentucky

Status

Recruiting

Address

Norton Diagnostic Center-Dupont (PET Scans)

Louisville, Kentucky, 40207

Norton Women & Children's Hospital, Louisville, Kentucky

Status

Recruiting

Address

Norton Women & Children's Hospital

Louisville, Kentucky, 40207

University of Michigan Hospitals, Ann Arbor, Michigan

Status

Recruiting

Address

University of Michigan Hospitals

Ann Arbor, Michigan, 48109

University of Michigan, Ann Arbor, Michigan

Status

Recruiting

Address

University of Michigan

Ann Arbor, Michigan, 48109

Barbara Ann Karmanos Cancer Institute, Detroit, Michigan

Status

Recruiting

Address

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201

Farmington Hills, Michigan

Status

Recruiting

Address

Karmanos Cancer Institute Weisberg Cancer Treatment Center

Farmington Hills, Michigan, 48334

Basking Ridge, New Jersey

Status

Recruiting

Address

Memorial Sloan Kettering Cancer Center at Basking Ridge

Basking Ridge, New Jersey, 07920

Middletown, New Jersey

Status

Recruiting

Address

Memorial Sloan Kettering Cancer Center at Monmouth

Middletown, New Jersey, 07748

Montvale, New Jersey

Status

Recruiting

Address

Memorial Sloan Kettering Cancer Center at Montvale

Montvale, New Jersey, 07645

Montefiore Medical Center, Bronx, New York

Status

Recruiting

Address

Montefiore Medical Center

Bronx, New York, 10467

Roswell Park Cancer Institute, Buffalo, New York

Status

Not yet recruiting

Address

Roswell Park Cancer Institute

Buffalo, New York, 14263

Commack, New York

Status

Recruiting

Address

Memorial Sloan Kettering Cancer Center at Commack

Commack, New York, 11725

Harrison, New York

Status

Recruiting

Address

Memorial Sloan Kettering Cancer Center at Westchester

Harrison, New York, 10604

New York, New York

Status

Recruiting

Address

Memorial Sloan Kettering Cancer Center - David H. Koch Center

New York, New York, 10021

New York, New York

Status

Recruiting

Address

Memorial Sloan Kettering Cancer Center (Outpatient Center)

New York, New York, 10065

Memorial Sloan Kettering Cancer Center, New York, New York

Status

Recruiting

Address

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

Uniondale, New York

Status

Recruiting

Address

Memorial Sloan Kettering Cancer Center at Nassau

Uniondale, New York, 11553

Gabrail Cancer Center Research, Canton, Ohio

Status

Terminated

Address

Gabrail Cancer Center Research

Canton, Ohio, 44718

University of TN Medical Center, Knoxville, Tennessee

Status

Recruiting

Address

University of TN Medical Center

Knoxville, Tennessee, 37920

Houston, Texas

Status

Recruiting

Address

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030

Swedish Cancer Institute, Seattle, Washington

Status

Recruiting

Address

Swedish Cancer Institute

Seattle, Washington, 98104

Swedish Medical Center, Seattle, Washington

Status

Recruiting

Address

Swedish Medical Center

Seattle, Washington, 98122