malignant hematology and stem cell transplant clinical...

Multiple Myeloma 4

Non-Hodgkin’s Lymphoma 8

CML 13

AML & MDS 14

Transplantation 19

A Message from Thomas Martin, MD

It’s been long coming but welcome to the UCSF Hematologic Malignancies

Research portfolio. This document provides a listing of the current open or

soon to be open therapeutic research protocols, with a brief description of

eligibility criteria. We have also included “Research Highlights” to highlight

some of the areas of focus at UCSF. We plan to update this listing/mailer

three to four times a year depending on accrual and opening of new studies.

You can e-mail or call for the most recent document or to inquire about study

availability at the e-mail and phone numbers listed below.

Malignant Hematology and Stem

Cell Transplant Clinical Protocols

Actively Enrolling

2016

Thomas Martin, MD

Director, Hematologic Malignancies Research Program

Hematology/Oncology Department, UCSF Medical Center

For clinical trial inquiries, please call:

Jenai Wilmoth, RN

[email protected]

415.514.6281

Research Highlights

CAR T-Cell Therapy at UCSF: Truly “Personalized” Medicine

Since the advent of imatinib for the treatment of chronic myeloid leukemia,

researchers studying hematologic malignancies have focused on developing

increasingly “personalized” therapies for patients with leukemia, lymphoma,

and myeloma.

Perhaps the most exciting therapeutic development in several decades is the

emerging technology of chimeric antigen receptor (CAR) T-cells. CAR T-cells

are created from a patient’s own T-cells, which, after collection via a standard

leukapheresis procedure, are genetically modified to recognize a disease-specific

antigen. These cells are then expanded ex-vivo and re-infused, allowing a patient’s

own immune system to be re-targeted against the underlying malignancy. The

best-studied antigen thus far for CAR T-cell therapy is CD19, a cell surface protein

found on the vast majority of lymphoid malignancies, including acute lymphoblastic

leukemia (ALL) and non-Hodgkin lymphoma (NHL).

UCSF is at the forefront of CAR T-cell development, with trials of CD19-directed

CAR T-cells for both relapsed/refractory ALL and NHL scheduled to open in late

2015 or early 2016. For more information, please contact:

Gabriel Mannis, MD (ALL; [email protected]) or

Aaron Logan, MD (ALL; [email protected]) or

Babis Andreadis, MD (NHL; [email protected]).

Gabriel Mannis, MD

mailto:[email protected]

mailto:[email protected]

FLT3 (+) Acute Myelogenous Leukemia: Dr. Cathy Smith

Mutations in Fms-Like Tyrosine Kinase 3 (FLT3), particularly internal tandem

duplication (ITD) mutations, are the most common mutations found in de novo AML

and confer a poor clinical prognosis. Over the past seven years at UCSF, we have

enrolled many patients in early phase clinical trials evaluating novel FLT3 inhibitors

in relapsed/refractory FLT3-mutant AML, with some early clinical responses.

Quizartinib was perhaps the first highly active FLT3 inhibitor and in a multinational

Phase II clinical trial in relapsed/refractory AML, quizartinib achieved a composite

complete remission (CRc) rate of 47% in relapsed refractory FLT3-ITD+ AML.

In translational studies done primarily at UCSF, Dr. Smith and colleagues found

that secondary FLT3 kinase domain mutations were the major cause of relapse in

patients receiving quizartinib. This work spurred the development of next

generation FLT3 inhibitors with activity against these quizartinib-resistant mutations

and formed the basis for clinical trials testing ponatinib, PLX3397 and ASP2215,

also conducted at UCSF. Most recently, ASP2215, a promising next generation

FLT3 inhibitor achieved a CRc rate of 50% in the national phase I/II clinical trial in

FLT3 mutant AML patients. UCSF was one of the largest enrolling centers on this

trial. We currently have more trials of ASP2215 and other novel FLT3 inhibitors in

pre-clinical and clinical development. Our program has and strives to continue to

pioneer further understanding of FLT3-mutant AML and we hope to bring the most

promising novel therapeutics to our patients with FLT3+ disease.

For more information, please contact:

Catherine Smith, MD ( [email protected])

Protocol Listings:

Multiple Myeloma

Relapsed and Refractory

1. NCT01084252 (CHR# 11-06563, CC# 11257): A Phase 1/2 Dose Escalation Safety,

Pharmacokinetic and Efficacy Study of Multiple Intravenous Administrations of a Humanized

Monoclonal Antibody (SAR650984) against CD38 in patients with selected CD38+ hematological

malignancies.

Principal Investigator: Thomas Martin, MD — [email protected]

Status: Phase 1 closed to accrual, Phase II expansion cohort to reopen in 2016

Eligibility: Includes but is not limited to the following criteria:

Relapsed Multiple Myeloma

Measurable disease (M-protein or SFLC)

≥ 3 prior lines of therapy including an IMiD and proteasome inhibitor

Normal kidney/liver function, ANC > 1,000, Platelets ≥ 50,000/mL, Hemoglobin > 8 g/dL

Treatment: IV anti-CD38 mAb single agent weekly x4, then every other week

Study Goals: Determine response rate and safety

More Information: https://clinicaltrials.gov/ct2/show/NCT01084252

2. NCT01749969 (CHR# 12-10124, CC# 12958): A Phase Ib Study of SAR650984 (anti-CD38 mAb) in Combination with Lenalidomide and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma.


Status: Open to Accrual


Diagnosis of Multiple Myeloma and documentation of at least 2 prior therapies

Relapsed or refractory disease

Karnofsky ≥ 60% performance status

No diagnosis or treatment of another malignancy within 3 years prior

Treatment: Lenalidomide, Dexamethasone, SAR650984

Study Goals: To determine the maximum tolerated dose of SAR650984 with Lenalidomide and

Dexamethasone in patients with relapsed or refractory multiple myeloma.


https://clinicaltrials.gov/ct2/show/NCT01084252


Multiple Myeloma

3. NCT02332850 (CHR# 14-14464, CC# 139511): A Phase I Study of SAR650984 (Anti-CD38 mAb) in Combination with Carfilzomib for the Treatment of Relapsed or Refractory Multiple Myeloma




Diagnosis of relapsed Multiple Myeloma, 2 prior lines of therapy

Documentation of prior treatment with an IMiD and proteasome inhibitor

Hemoglobin ≥ 8.0 g/dl (without transfusion within the previous 7 days), ANC > 1,000, Platelet count ≥ 50,000/mL

Confirmed relapsed or refractory disease from immediately prior MM therapy

Measurable disease

No diagnosis or treatment for another malignancy within 3 years of enrollment (some

exceptions)

Treatment: Antibody investigational product infusion (SAR65094), Carfilzomib 27 mg/m2

Study Goals: Find the Maximum Tolerated Dose, then expand that dose to a larger number of patients to determine safety parameters.


4. NCT02431208 (CC#15254, MMRC—068): A Phase 1b study of the safety and pharmacokinetics of MPDL3280A (anti PDL1 antibody) alone or in combination with Lenalidomide in patients with multiple myeloma (relapsed and post autologous stem cell transplant)


Status: Opening in January 2016


Relapsed Multiple Myeloma with measurable disease (M-protein > 0.5, LC > 100 g/L)

ECOG performance status score of 2 or less

LVEF greater than or equal to 40%

2-4 prior therapies

Lab Results: ANC ≥ 1,000 cells/mL, AST/ALT ≤ 2.5 x ULN, Platelet count ≥ 50,000/mL, T-bilirubin ≤ 1.5 mg/dL, Creatinine ≤ 2.0 mL/dL, Creatinine Clearance ≥ 40 mL/min, serum calcium at or below ULN

Treatment: MPDL3280A as a single agent, or in combination with lenalidomide

Study Goals: Evaluate the safety and pharmacokinetics of MPDL3280A alone or in combination with lenalidomide.




Multiple Myeloma

Non Therapeutic & Tissue Banking

5. MMTI (CC#102510): Database and Sample Repository for Patients with Plasma Cell Disorders


Jeffrey Wolf, MD — [email protected]

Status: Enrolling

Eligibility:

All patients seen at UCSF with plasma cell disorders

6. MMRC (CC#08253): Multiple Myeloma Research Consortium Ancillary Tissue Collection


Jeffrey Wolf, MD — [email protected]

Status: Enrolling

Eligibility:

All patients undergoing bone marrow biopsy at UCSF

Protocols Opening Soon

7. NCT02253316 (CC# 152514): A Phase II Study of IRD (Ixazomib, Lenalidomide & Dexamethasone) for Consolidation Therapy Post Autologous Stem Cell Transplantation followed by Maintenance Ixazomib or Lenalidomide for Multiple Myeloma

Principle Investigator: Thomas Martin, MD — [email protected]

Status: Will Open January 2016


Diagnosis of symptomatic multiple myeloma

No Grade ≥ 1 peripheral neuropathy with pain on clinical examination during screening

Subject not eligible if they require anticoagulation with Warfarin or other vitamin K antagonist

At least 2 cycles of initial systemic therapy within the last 12 months

ECOG performance status of 0,1 or 2

Lab Results: ANC ≥ 1,000/mm3, Platelet Count ≥ 75,0000/mm

3, T-Bilirubin ≤ 1.5 x ULN,

ALT/AST ≤ 3 x ULN, Creatinine Clearance ≥ 30 mL/min

Treatment: Consolidation therapy consisting of four 28-day cycles of IRD (ixazomib, lenalidomide & dexamethasone)

Study Goals: Determine efficacy and tolerability of IRD for consolidation therapy post ASCT

More Info: https://clinicaltrials.gov/ct2/show/NCT02253316


Multiple Myeloma

8. CC#15959: TED14154: An Open-Label Dose-Escalation and Multi-Center Study to Evaluate the Safety and Pharmacokinetics of SAR650984 in Patients with Relapsed/Refractory Multiple Myeloma

Principle Investigator: Thomas Martin, MD — [email protected]

Status: Opening Soon


Must have relapsed Multiple Myeloma

Must have known diagnosis of Multiple Myeloma and measurable disease

Must have had at least 3 prior lines of therapy including treatment with an IMiD and a proteasome inhibitor

Must have evidence of disease progression

Must have received an alkylating agent

Must have achieved an MR or better to at least one prior line of therapy

Patients must not have an IGM subtype

No previous treatment with any anti-CD38 therapy

Lab Results: ANC ≤ 1,000/mm3, Hemoglobin < 8.0 g/dL, Platelet count ≤ 50,000/mm

3

Treatment: Single Agent SAR650984

Study Goals: Evaluate Safety and Efficacy

More Info: Pending

Non-Hodgkin’s Lymphoma

1. NCT01511562 (CHR# 13-10725, CC# CALGB-51101): A Randomized Phase II Trial of

Myeloablative vs. Non-Myeloablative Consolidation Chemotherapy for Newly Diagnosed Primary CNS B-Cell Lymphoma

Principal Investigator: James Rubenstein, MD — [email protected]



Diagnosis of primary CNS diffuse large B-cell lymphoma

No evidence or history of NHL outside of CNS

No HIV, Hepatitis B, or Hepatitis C

No prior chemotherapy/radiation therapy for lymphoma

Lab Values: ANC ≥ 1,500/mcL and Platelets ≥ 100,000/mcL, Creatinine Clearance ≥ 50 mL/min, T-Bilirubin ≤ 3 mg/dL, AST+ALT ≤ 2 x ULN

Treatment: 5 cycles chemotherapy with methotrexate, temozolomide, rituximab and cytarabine. Followed by randomized consolidation therapy with allopathic transplant or consolidation therapy with cytarabine and etoposide.

Study Goals: Compare two-year progression-free survival of patients treated with each regimen


2. NCT01542918 (CHR# 11-08133, CC# 112530): A Phase I Study of Lenalidomide Plus Rituximab for Recurrent/Refractory CNS and Intraocular Lymphoma

Principal Investigator: James Rubenstein, MD — [email protected]



Tumors must be CD20+ on prior pathologic analysis

Must have an Ommaya reservoir inserted as part of standard clinical care prior

to initiation of study treatment

Renal function assessed by calculated creatinine clearance

Able to take aspirin daily (81 or 325 mg)

No active viral infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)

No IV Rituximab within 30 days of starting therapy

Lab Values: ANC ≥ 1,500/mcL, Platelets ≥ 50,000/mcL, T-bilirubin ≤ 1.5 x ULN, AST/ALT ≤ 3 x ULN

Treatment: Lenalidomide (Revlimid) only, 21 days on 7 days off. Weekly visits for 4 months,

then monthly.

Treatment 2: Lenalidomide + Rituximab

Study Goals: Evaluate the safety and efficacy of Lenalidomide in patients with recurrent CNS NHL

and intraocular NHL. Establish a safe and reliable recommended dose and schedule.





Relapsed and Refractory

3. NCT01902225 (CHR# 11-07575, CC#112516): A Multicenter Phase I Dose-Finding and Preliminary

Efficacy Study of the Histone Deacetylase Inhibitor Romidepsin (Istodax®) in Combination

With Doxorubicin HCl Liposomal (Doxil®) for the Treatment of Adults With Relapsed or Refractory

Cutaneous T-cell Lymphoma

Principal Investigator: Ai Weiyun, MD — Ai. [email protected]



Measurable Stage IB-IVB relapsed or refractory cutaneous T-cell lymphoma

2 prior lines of skin-directed therapy or one prior line of systemic therapy

Life expectancy > 90 days

Lab Values: ANC ≥ 750, Platelets ≥ 75,000/mm3, T-Bilirubin ≤ 2 x ULN,

AST/ALT ≤ 3 x ULN, Calculated Creatinine Clearance ≥ 30 mL/min

Treatment: Doxil 20 mg/m2 on day 1, romidepsin 8-14mg/m

2 on days 1, 8 and 15, every 28 days,

until 2 cycles beyond the best response, 8 cycles, or disease progression.

Study Goals: Dose finding and preliminary efficacy study


4. NCT01555541 (CHR# 11-07843, CC# 112525): A Phase II Study of Intensive Consolidation and Stem Cell Mobilization Therapy with Ofatumumab, Etoposide, and High-Dose Ara-C (OVA), followed by Autologous Stem Cell Transplantation in High-Risk Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Principal Investigator: Charalambos Andreadis, MD — [email protected]



Diagnosis of refractory or relapsed CD20+ diffuse large B-cell lymphoma or primary mediastinal B-cell lymphoma

Refractory to or relapse following a rituximab/anthracycline first-line regimen

High-risk disease

No more than three prior chemotherapy regimens

Treatment: Ofatumumab, Etoposide, Ara-C (OVA), Autologous Transplant

Study Goals: Demonstrate the efficacy of OVA and study the safety and tolerability of OVA





5. NCT02187133 (CHR# 14-13799, CC# 14251): A Phase Ib Dose Escalation Trial of Carfilzomib in Combination with Bendamustine and Rituximab in Patients with Relapsed or Refractory Non-Hodgkin’s Lymphoma




Small Cell, Marginal Zone, Follicular, Mantle Cell, Diffuse Large B Cell

Relapsed or refractory disease after 2 but not more than 4 lines of therapy

Measurable disease

Life expectancy ≥ 3 months

No prior treatment with carfilzomib

Lab Values: ANC ≥ 1.0 x109/L, Hemoglobin ≥ 8 g/dL, Platelet Count ≥ 75 x 10

9

independent of platelet transfusion, AST/ALT ≤ 3 x ULN, Direct Bilirubin ≤ 2 mg/dL, Creatinine Clearance ≥ 30 mL/min

No prior Allogeneic transplant

Treatment: Bendamustine, Carfilzomib, Rituximab

Study Goals: Evaluate the safety and tolerability of Carfilzomib in combination with Bendamustine and Rituximab in patients with relapsed or refractory NHL. Determine the recommended phase II dose.


6. NCT0222751 (CC# 142511): A Phase 2b Open-Label, Randomized Two-Arm Study of Selinexor

(KPT- 330) with Low Dose Dexamethasone in Patients with Relapsed/Refractory Diffuse Large B-Cell

Lymphoma (DLBCL).




Pathologically confirmed DLBCL

ECOG performance status of < 2

Documented evidence of disease progression

Have previously received at least 2 but no more than 4 previous systemic multi-agent

regimens for the treatment of DLBCL

Measurable Disease

Off systemic therapy for 14 weeks

Platelet Count < 75

Treatment: Selinexor (a nuclear export inhibitor)

Study Goals: Demonstrate clinical benefit of SPT- 330 in patients with relapsed/refractory diffuse large B-cell lymphoma.





Previously Untreated

7. NCT01193842 (CHR# 12-08650, CC# AMC-075): A sequential Phase 1/Randomized Phase II Trial of Vorinostat and risk-adapted chemotherapy with Rituximab in HIV-Related B-Cell Non-Hodgkin’s Lymphoma

Principal Investigator: Lawrence Kaplan, MD – [email protected]



Previously untreated disease

Confirmed HIV infection by ELISA or western blot or federally approved test

No CNS involvement including parenchymal brain or spinal cord lymphoma, or known

leptomeningeal disease

Treatment: EPOCH, Rituxan, Rituximab, Vorinostat, Zolinza

Study Goals: Determine the recommended phase II dose of vorinostat to use in combination with

R-CHOP (in low-risk disease) or R-DA-EPOCH (in high risk disease) in subjects with HIV-associated diffuse large B-Cell lymphoma.



8. NCT02445248 (CC#152512): A Phase II, Single Arm, Multicenter Trial to Determine the Efficacy and Safety of CTL019 in Adult Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

Principle Investigator: Charalambos Andreadis, MD — [email protected]

Status: Will open December 2015


Confirmed Diagnosis of Diffuse Large B-Cell Lymphoma

Relapsed or refractory disease after ≥ 2 lines of chemotherapy and either having failed autologous HSCT, or being ineligible for Autologous HSCT

Measurable disease at time of enrollment

Lab Results: Creatinine of ≤ 1.5 x ULN, ALT ≤ 5 x ULN, Bilirubin ≤ 2.0 mg/dL

No prior treatment with anti-CD19/anti-CD3 therapy

No prior treatment with any gene therapy product

No active CNS involvement by malignancy

Life expectancy ≥ 12 weeks without chemotherapy

No prior allogeneic HSCT

Not positive for HIV

Treatment: Single dose of 1 to 5 x 108 of autologous CTL019 transduced cells via intravenous infusion

Study Goals: Determine the efficacy and safety of CTL019 in adult DLBCL patients





9. NCT02440685 (CC# 152516): A Phase 1/2, Open-Label, Uncontrolled, Multiple-Dose Escalation, Cohort Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Effica-cy of ASN002 in Relapsed/Refractory Lymphoma and Advanced Solid Tumors

Principle Investigator: Lawrence Kaplan, MD — [email protected]

Status: Will Open January 2016


Have not received or must be ineligible to receive a Stem Cell Transplant

ECOG performance of 0-2

Radiographically evaluable tumor by 2014 Lugano Classification recommendations

Fully recovered from reversible effects of prior antineoplastic therapy

Lab Results: ANC ≥ 1,000/mL, Platelets ≥ 75,000/mL, Hemoglobin ≥ 8 g/dL, ALT/AST≤ 3.0 x ULN, T-Bilirubin ≤ 2 x ULN, Creatinine ≤ 1.5 x ULN

No prior chemotherapy regimens within 4 weeks of Day 1

Must not have difficulty swallowing medications

Treatment: ASN002 administered orally, planned doses are 10, 20, 30, 40 and 50 mg q12H

Study Goals: To evaluate the safety and tolerability of ASN002 including dose-limiting toxicities and the maximum tolerated dose.



Chronic Myelogenous Leukemia

1. NCT01850004 (CHR# 13-12793, CC132512): Open-Label single arm Phase 2 study evaluating Dasatinib therapy discontinuation in patients with chronic phase chronic myeloid leukemia (CP– CML) with stable complete molecular response (CMR) DASFREE

Principal Investigator: Neil Shah, MD — [email protected]



Diagnosis of CP-CML

On treatment with dasatinib for a minimum of 2 years at time of enrollment

In dasatinib-induced complete molecular remission

Adequate renal function and hepatic function

Life expectancy of ≥ 1 year

Treatment: Possible dasatinib

Study Goals: Assess rate of MMR at 12 months after dasatinib discontinuation without re-starting

dasatinib.



2. NCT02269267 (CC# 15257): The Life After Stopping Tyrosine Kinase Inhibitors Study (The LAST Study)

Primary Investigator: Neil Shah, MD PhD — [email protected]

Status: Opening late November 2015


Diagnosed with CML in chronic phase

Currently taking imatinib, dasatinib, nilotinib, or bosutinib

On TKI therapy for at least 3 years

Undetectable BCR-ABL by PCR for at least 2 years

Undetectable PCR at least 3 times prior to screening

No resistance to any TKI

Must not have had any prior hematopoietic stem cell transplantation

Treatments: Standard RQ-PCR testing for molecular recurrence Study Goals: Compare patient health status before and after stopping TKIs to develop a scoring system for patient risk of molecular recurrence after stopping TKI.




Acute Myelogenous/Lymphoblastic Leukemia & MDS

Relapsed/Refractory 1. NCT02109627 (CHR# 13-12499, CC# 139510): A Phase Ib Study of Ficlatuzumab with High Dose

Cytarabine in Relapsed and Refractory AML.




Relapsed or refractory AML

Prior induction therapy included no more than two cycles of cytotoxic chemotherapy

One induction cycle must have consisted of an anthracycline or anthracenedione and

cytarabine combination with reasonable schedule/dose (according to discretion of

investigator)

Lab Values: T-Bilirubin ≤ 2.0 mg/dL, AST/ALT ≤ 3 x ULN, Creatinine ≤ 2.0 mg/dL

Treatment: Ficlatuzumab, an anti-HGF antibody, is administered intravenously on Day 0, 14, 28, and 42.

Study Goals: Assess the safety and tolerability, determine maximum tolerated dose of Ficlatuzumab in combination with HiDAC in patients with relapsed or refractory AML.


2. NCT02319369 (CC# 14956): A Phase 1 Dose Escalation Study of DS 3032B, and Oral MDM2 Inhibitor, in Subjects with Acute Myelogenous Leukemia (AML), Acute Lymphocytic Leukemia (ALL), Chronic Myelogenous Leukemia (CML) in Blast Phase, or High Risk Myelodysplastic Syndrome (MDS)

Principal Investigator: Rebecca Olin, MD — [email protected]



Refractory or relapsed AML or ALL, CML in blast phase or high-risk MDS

Must have adequate renal function and hepatic function (Creatinine Clearance ≥ 60 mL/min or Creatinine ≤ 1.5 x ULN, AST/ALT ≤ 3 x ULN, Bilirubin ≤ 1.5 x ULN)

Must have adequate blood clotting function

Must not have a diagnosis of acute promyelocytic leukemia

No prior treatment with an MDM2 inhibitor

Treatment: DS-3032b

Study Goals: Assess safety and tolerability and identify a Maximum Tolerated Dose.





3. NCT02043587 (CC# 14256): A Phase II Study of Punctual, Cyclic, and Intensive Chemotherapy

with Liposomal Cytarabine (Depocyt®) CNS Prophylaxis for Adults With Acute Lymphoblastic

Leukemia and Lymphoblastic Lymphoma

Principal Investigator: Lloyd Damon, MD — [email protected]



Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma as defined by WHO

ECOG performance status of 0,1 or 2

Lab Values: Total bilirubin < 2 mg/dL , Serum creatinine < 2 mg/dL

Untreated disease except for corticosteroids, hydroxyurea, leukapheresis, and/or tyrosine kinase inhibitors for up to 2 weeks prior to initiation of study therapy

No recurrent or chronic pancreatitis

No uncontrolled diabetes mellitus

Treatment: Intensive chemotherapy with Depocyt CNS prophylaxis

Study Goals: Improve survival for adults with acute lymphoblastic leukemia or acute lymphoblastic

lymphoma by reducing systemic and CNS relapse.


4. NCT02282215 (CC# 142513): An Open-Label Phase 2 Prospective, Randomized, Controlled Study

of CLT-008 Myeloid Progenitor Cells as a Supportive Care Measure During Induction Chemotherapy for Acute Myeloid Leukemia.



Eligibility:

Age > 55

New AML diagnosis

ECOG performance of 0-2 at time zero (screening)

Serum bilirubin ≤ 1.5 times upper limits of normal

Cannot have any history of malignance requiring treatment other than surgery

Cannot have ALM subtype M3

Treatment: CLT-008 with G-CSF

Study Goals: To study the safety and efficacy of CLT-008 as a supportive care measure after induction therapy for patients with acute myeloid leukemia.



https://clinicaltrials.gov/ct2/show/NCT02282215?titles=An+Open-Label+Phase+2+Prospective%2C+Randomized%2C+Controlled+Study+of+CLT-008+Myeloid+Progenitor+Cells+as+a+Supportive+Care+Measure+During+Induction+Chemotherapy+for+Acute+Myeloid+Leukemia&rank=1


5. NCT02074839 (CC# 15255): A Phase 1, Multicenter, Open-Label, Dose-Escalation and Expansion, Safety, Pharmacokinetic, Pharmacodynamic, and Clinical Activity Study of Orally Administered AG-120 in Subjects with Advanced Hematologic Malignancies with an IDH1 Mutation

Principal Investigator: Gabriel Mannis, MD — [email protected]

Status: Open Date: Open to Accrual


Have an advanced hematologic malignancy

Documented IDH1 gene-mutated disease

ECOG PS of 0-2

Lab Results: Platelet Count > 20,000, T-Bilirubin ≤ 1.5 x ULN, AST/ALT/ALP ≤ 3.0 x ULN, Serum Creatinine ≤ 2.0 x ULN, Creatinine Clearance > 40 mL/min

Treatment: AG-120

Study Goals: Evaluate the safety, pharmacokinetics, pharmacodynamics and clinical activity of AG-120.



6. CC#152513: A Phase 3 Open-label, Multicenter, Randomized Study of ASP2215 versus salvage Chemotherapy in Patients with Relapsed or Refractory Acute Myeloid Leukemia (AML) with FLT3 Mutation

Principle Investigator: Rebecca Olin, MD — [email protected]

Status: Will Open Late January 2016


Diagnosis of primary AML or AML secondary to myelodysplastic syndrome

Refractory or relapsed after first-line AML therapy (with or without HSCT)

Positive for FLT3 activating mutation in bone marrow or whole blood

ECOG performance status of ≤ 2

Lab Results: AST/ALT ≤ 2.5 x ULN, T-bilirubin ≤ 1.5 x ULN, creatinine ≤ 1.5 x ULN

No diagnosis of acute promyelocytic leukemia

No prior salvage therapy for refractory disease

No clinically active central nervous system leukemia

Has received prior treatment with ASP2215 or other FLT3 inhibitors

Treatment: ASP2215 120 mg administered once daily (administered orally)

Study Goals: Determine clinical benefit of ASP2215





7. CC# 152510: The ROCKET Study: A Phase 2, Single-Arm, Multicenter Trial to Determine the Efficacy and Safety of JCAR015 in Adult Subjects with Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia.

Principle Investigator: Gabriel Mannis, MD — [email protected]

Status: Will Open Mid December 2015


Diagnosis of B-cell ALL by flow cytometry

Relapsed or Refractory B-cell ALL

Bone Marrow with morphological evidence of disease (≥ 5% blasts)

Evidence of CD19 expression via flow cytometry

ECOG performance status between 0 and 2 at screening

Lab Results: Creatinine ≤ 1.5 x ULN, ALT ≤ 5 x ULN,

Must not have Burkitt’s lymphoma/leukemia or CLM lymphoid blast crisis

No prior malignancy unless no evidence of active disease for > 5 years before screening

No prior treatment with gene therapy product

No treatment with alemtuzumab within 6 months prior to leukapheresis, or treatment with clofarabine or cladribine within 3 months prior to leukapheresis

Treatment: JCAR015 (CAR+ CD3+T cells, Cryostor C210, Plasma-Lyte A and Human Serum Albumin)

Study Goals: Determine safety and efficacy of JCAR015

8. NCT02282215 (CC# 142513): An open-label Phase 2 prospective, randomized, controlled study of CLT-008 myeloid progenitor cells as a supportive care measure during induction chemotherapy for acute myeloid leukemia.


Status: Open To Enrollment


Greater than 55 years of age

No AML subtype M3 (promyelocytic leukemia)

Acute myeloid leukemia arising de novo

Treatment with an established chemotherapy regimen

ECOG performance status of 0-2

No previous chemotherapy for AML

Treatment: CLT-008, G-CSF

Study Goals: Explore the safety and efficacy of CLT-008 as a supportive care measure after induction chemotherapy for patients with AML.




9. CC#152511: A Phase 1/2 Multi-Center Study Evaluating the Safety and Efficacy of KTE-C19

in Adult Subjects with Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (r/r ALL )

Principal Investigator: Aaron Logan, MD — [email protected]

Status: Pending


Relapsed/Refractory B-precursor ALL as evidenced by 5% or more blasts in the bone marrow

ECOG performance of 0 or 1

Lab Results: ANC ≥ 500/uL, Platelet Count ≥ 50,000/uL, ALC ≥ 100//uL, Serum Creatinine ≤ 1.5 mg/dL, Serum ALT/AST ≤ 5 x ULN, T-Bilirubin ≤ 1.5 mg/dL

No diagnosis of Burkitt’s leukemia/lymphoma

No subjects with CNS-3 disease

No known mixed-lineage leukemia rearrangements

No active acute GVHD equal to or greater than a grade 2

No prior CD-19 directed therapy

Treatment: Conditioning chemotherapy regimen or fludarabine and cylophosphamide followed by single infusion of CAR-T cells

Study Goals: To determine the safety of and overall response to KTE-C19



Transplant Protocols

1. NCT01877655 (CHR# 14-13435, CC# 13253): A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial to Evaluate the Protective Efficacy and Safety of a Therapeutic Vaccine, ASP0113, in Cytomegalovirus (CMV) - Seropositive Recipients Undergoing Allogeneic, Hematopoietic Cell Transplant (HCT)




CMV-seropositive HCT recipient

Donor must be 7/8 or 8/8 HLA (ABC/DR) matched sibling or unrelated donor

Graft may be PBSC or BM

Patient excluded if HCT-CI ≥ 4

Subject cannot have received any prior HCT or have residual cGVHD

Subject will be excluded if they have a platelet count < 50,000 mm3 within 3 days prior

to randomization

Scheduled to receive an allogeneic peripheral blood stem cell or bone marrow transplant

Treatment: 5 doses of Plasmid DNA vaccine

Study Goals: Assess adequacy of components. Determine the safety of ASP0113 in patients

undergoing allogeneic HCT. Evaluate efficacy over placebo in incidence of the primary composite

endpoint through one-year post-transplant.


2. NCT02268526 (CHR# 14-15387, CC# 14259): A Multi-Center, Randomized, Double-Blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of CSJ148 Compared to Placebo to Prevent

Human Cytomegalovirus (HCMV) Replication in Stem Cell Transplant Patients (CCSJ148X2201)




Scheduled to undergo allogeneic bone marrow, peripheral blood stem cell, or cord blood transplantation

Patient seropositive for HCMB before transplantation

No detectable HCMV infection.

Weight must be between 45-120 kg to participate in the study.

Treatment: CSJ148, randomized administration as 2 hour infusion day before transplant conditioning regimen begins. 3.5 month treatment period with CSJ148 administered on a monthly, tri-weekly,

bi-weekly, or weekly basis.

Study Goals: Assess the efficacy of CSJ148 in preventing active HCMV infection. Assess the safety and tolerability of CSJ148 when administered to stem cell transplant recipients.




Transplant Protocols

3. NCT02195869 (CC# 15251): A Multicenter Open-Label Phase 1b/2 Study of Ibrutinib in Steroid

Dependent or Refractory Chronic Graft versus Host Disease


Status: Open Date: Open to Enrollment


Steroid dependent or refractory classic chronic GVHD disease

No more than 3 previous treatments for cGVHD

Receiving baseline systemic glucocorticoid therapy at study entry

Karnofsky performance status ≥60

No known or suspected active GVHD

No current treatment with sirolimus and either cyclosporine or tacrolimus

Treatment: Ibrutinib

Study Goals: Asses the safety and clinical efficacy of ibrutinib in subjects with steroid dependent or refractory Chronic Graft Versus Host Disease.



malignant hematology and stem cell transplant clinical...

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