Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Lymphoma

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Leukemia, Prolymphocytic

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Lymphosarcoma

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Antirheumatic Agents

All Drugs and Chemicals

Auranofin

Auranofin 6 mg orally in the morning / 6 mg orally in the evening

6 mg twice a day for a total of 12 mg total daily dose

auranofin

Suman Kambhampati, MD

The purpose of this study is to evaluate the safety and effectiveness of auranofin to treat patients with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or prolymphocytic lymphoma (PLL).

Phase I and II Study of Auranofin in Chronic Lymphocytic Leukemia (CLL)

A Phase I Phase II Two-Step Study of the Oral Gold Compound Auranofin in Chronic Lymphocytic Leukemia (CLL)/ Small Lymphocytic Lymphoma (SLL)/ Prolymphocytic Lymphoma (PLL)

The Leukemia and Lymphoma Society

Kansas Bioscience Authority

Therapeutics for Rare and Neglected Diseases (TRND)

University of Kansas Medical Center

Antineoplastic Agents

Amino Acids

Venetoclax

Obinutuzumab

Acalabrutinib

Rituximab

Antineoplastic Agents, Immunological

Immunologic Factors

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Dose-escalation and dose-expansion phases will be conducted for relapsed/refractory (R/R) participants with CLL. In dose-escalation phase, participants will receive oral acalabrutinib Dose 1 once daily (QD), later the dose was switched to Dose 2 twice daily (BID) per Amendment 02. In dose- expansion phase, participants will receive oral acalabrutinib Dose 2 BID in 28-day continuous cycles; and will receive intravenous (IV) infusion of obinutuzumab for total 6 cycles (from Cycles 2 to 7) as on Cycle 2 Day 1 participants will receive Dose 1, on Cycle 2 Day 2 participants will receive Dose 2, on Cycle 2 Days 8 and 15 participants will receive Dose 3, and on Day 1 of Cycles 3 to 7 participants will receive Dose 3. Participants will continue to receive acalabrutinib Dose 2 BID until disease progression, an unacceptable drug-related toxicity, or per the investigator the study treatment is intolerable or no longer in participant's best interest, whichever occurs first.

Dose-escalation and dose-expansion phases will be conducted for treatment-naïve participants with CLL/ small lymphocytic lymphoma (SLL). In dose-escalation phase, participants will receive oral acalabrutinib Dose 2 BID in first cycle (28-day cycle). In dose- expansion phase, participants will receive oral acalabrutinib Dose 2 BID in 28-day continuous cycles; and will receive IV infusion of obinutuzumab for total 6 cycles (from Cycles 2 to 7) as on Cycle 2 Day 1 participants will receive Dose 1, on Cycle 2 Day 2 participants will receive Dose 2, on Cycle 2 Days 8 and 15 participants will receive Dose 3, and on Day 1 of Cycles 3 to 7 participants will receive Dose 3. Participants will continue to receive acalabrutinib Dose 2 BID until disease progression, an unacceptable drug-related toxicity, or per the investigator the study treatment is intolerable or no longer in participant's best interest, whichever occurs first.

The R/R participants with CLL will receive oral acalabrutinib, IV infusion of rituximab, and oral venetoclax. Participants will receive acalabrutinib Dose 2 BID in 28-day continuous cycles until disease progression, an unacceptable drug-related toxicity, or per the investigator the study treatment is intolerable or no longer in participant's best interest, whichever occurs first. Participants will receive rituximab for total 6 cycles (from Cycles 2 to 7) as Dose 1 on Cycle 2 Day 1, followed by Dose 1 every 3 weeks (Q3W) for 3 doses, then every 4 weeks (Q4W) for 5 doses (total 9 infusions through the end of Cycle 7). Participants will receive venetoclax weekly ramp-up schedule over 5 weeks from Cycles 3 to 15, Dose 1 QD for 1 week on Cycle 3 Day 1, Dose 2 QD for 1 week on Cycle 3 Day 8, Dose 3 QD for 1 week on Cycle 3 Day 15, Dose 4 QD for 1 week on Cycle 3 Day 22, and Dose 5 QD from Cycle 4 Day 1 until completion of Cycle 15.

The treatment-naïve participants with CLL will receive oral acalabrutinib, IV infusion of obinutuzumab, and oral venetoclax. Participants will receive acalabrutinib Dose 2 BID in 28-day continuous cycles until disease progression, an unacceptable drug-related toxicity, or per the investigator the study treatment is intolerable or no longer in participant's best interest, whichever occurs first. Participants will receive obinutuzumab for total 6 cycles (from Cycles 2 to 7) as Dose 1 on Cycle 2 Day 1, Dose 2 on Cycle 2 Day 2, Dose 3 on Cycle 2 Days 8 and 15, and Dose 3 on Day 1 of Cycles 3 to 7. Participants will receive venetoclax weekly ramp-up schedule over 5 weeks from Cycles 3 to 15 as Dose 1 QD for 1 week on Cycle 3 Day 1, Dose 2 QD for 1 week on Cycle 3 Day 8, Dose 3 QD for 1 week on Cycle 3 Day 15, Dose 4 QD for 1 week on Cycle 3 Day 22, and from Cycle 4 Day 1 participants will receive Dose 5 QD until completion of Cycle 15.

Participants will receive oral acalabrutinib in Cohorts 1, 2, 3, and 4. The details are mentioned in the cohort description.

acalabrutinib

Participants will receive intravenous obinutuzumab in Cohorts 1, 2, and 4. The details are mentioned in the cohort description.

Participants will receive oral venetoclax in Cohorts 3 and 4. The details are mentioned in the cohort description.

Participants will receive intravenous rituximab in Cohort 3. The details are mentioned in the cohort description.

AstraZeneca Study Information Center

To evaluate the safety and preliminary efficacy of acalabrutinib in combination with obinutuzumab in 4 separate cohorts of participants.

A Phase 1b Study of ACP-196 in Combination with Obinutuzumab for Participants with Relapsed/Refractory or Untreated chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL)/ prolymphocytic leukemia (PLL).

Study started with two cohorts, on Acalabrutinib and Obinutuzumab, cohort 1 for relapsed or refractory participants and cohort 2 for treatment naïve participants. Then for longer survival data and combination therapy, two new cohorts added to the study, cohort 3 with relapsed or refractory participants on Acalabrutinib, Rituximab and Venetoclax, and cohort 4 with treatment naïve participants on Acalabrutinib, Obinutuzumab and Venetoclax.

Primary endpoints: For Cohorts 1 and 2, the ORR (PR or better) at the 12-month response assessment will be calculated and 95% exact binomial confidence interval (CIs) will be provided. For Cohorts 1 to 4, toxicities will be tabulated by type and grade using NCI-CTCAE (National Cancer Institute - Common Terminology Criteria for Adverse Events) version 4.03 criteria or higher and displayed in summary form.

Currently, study is in maintenance phase and we don't expect a major change in the near future.

Acalabrutinib in Combination With Anti-CD20 and Venetoclax in Relapsed/Refractory or Untreated CLL/SLL/PLL

A Phase 1b Study of ACP-196 in Combination With Obinutuzumab for Patients With Relapsed / Refractory or Untreated CLL/SLL/PLL

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

The OR is complete remission (CR), incomplete CR (CRi), nodular partial remission (nPR), or partial remission (PR) for at least 2 months. For CLL, CR:lymphocytes (lympho) \<4×10\^9/L, normocellular bone marrow (BM) \<30% lympho, no B-lymphoid nodules, normal lymph nodes (NLN), liver and spleen (L/S), absolute neutrophils (ANC) \>1.5×10\^9/L, platelets \>100×10\^9/L, hemoglobin (Hb) \>11g/dL; CRi: lympho \<4×10\^9/L, hypocellular BM, NLN, L/S, persistent anemia/thrombocytopenia/neutropenia; nPR: CR with present lymphoid nodules (NL); PR: \>=50% reduction in lymphadenopathy and/or enlargement of L/S or lympho (\<5×10\^9/L or \>=50% decrease from baseline), criteria of ANC/platelets/Hb per CR or \>=50% improvement over baseline. Hematology without exogenous growth factors/transfusion. For SLL, CR: no disease/disease-related symptoms, normal/\<=1cm LN, no enlargement of L/S/NL, disease-free BM; PR: \>=50% decrease in dominant masses with no size increase/new lesions, and \>=50% reduction of nodules in S/L.

An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.

Participants with treatment-emergent CTCAE Grade 3 or 4 abnormalities in laboratory parameters are reported. Laboratory analysis included hematology, clinical chemistry, and immunology.

Participants with abnormal vital signs (blood pressure, respiratory rate, heart rate, temperature, and body weight) reported as TEAEs are reported.

The ECOG Performance Status assessed participant's performance status on 5 point scale: 0=Fully active/able to carry on all pre-disease activities without restriction; 1=restricted in physically strenuous activity, ambulatory/able to carry out light or sedentary work; 2=ambulatory (\>50% of waking hours), capable of all self-care, unable to carry out any work activities; 3=capable of only limited self care, confined to bed/chair \>50% of waking hrs; 4=completely disabled, cannot carry on any self care, totally confined to bed/chair; 5=death. Shift from baseline (Days -28 to -1) to worst Grade 3 and/4 in EOCG status are reported.

For CLL, CR: lymphocytes \< 4×10\^9/L, normocellular bone marrow \< 30% lymphocytes, no B-lymphoid nodules, normal lymph nodes, liver and spleen, absolute neutrophils \> 1.5×10\^9/L, platelets \> 100×10\^9/L, hemoglobin \> 11g/dL. Hematology without exogenous growth factors/ transfusion. For SLL, CR: no disease/disease-related symptoms, normal/\<=1 cm lymph nodes, no enlargement of liver/spleen/lymphoid nodules, disease-free bone marrow.

For CLL, CR: lymphocytes \<4×10\^9/L, normocellular bone marrow (BM) \<30% lymphocytes, no B-lymphoid nodules, normal lymph nodes, liver, and spleen, absolute neutrophil count \>1.5×10\^9/L, platelets \>100×10\^9/L, hemoglobin \> 11g/dL; CRi: lymphocytes \< 4×10\^9/L, hypocellular BM, normal lymph nodes, liver, and spleen, persistent anemia/thrombocytopenia/neutropenia. Hematology without exogenous growth factors/transfusion. For SLL, CR: no disease/disease-related symptoms, normal/\<=1 cm lymph nodes, no enlargement of liver/spleen/lymphoid nodules, disease-free BM. MRD negativity was determined in bone marrow by flow cytometry.

The OR is complete remission (CR), incomplete CR (CRi), nodular partial remission (nPR), or partial remission (PR) for at least 2 months. For CLL, CR: lymphocytes \<4×10\^9/L, normocellular bone marrow \<30% lymphocytes, no B-lymphoid nodules, normal lymph nodes (NLN), liver and spleen (L/S), absolute neutrophils (ANC) \>1.5×10\^9/L, platelets \>100×10\^9/L, hemoglobin (Hb) \>11g/dL; CRi: lymphocytes \<4×10\^9/L, hypocellular bone marrow, NLN, L/S, persistent anemia/thrombocytopenia/neutropenia; nPR: CR with present lymphoid nodules; PR: \>=50% reduction in lymphadenopathy and/or enlargement of L/S or lymphocytes (\<5×10\^9/L or \>=50% decrease from baseline), criteria of ANC/platelets/Hb per CR or \>=50% improvement over baseline. Hematology without exogenous growth factors/transfusion.

The DoR is defined as the time from the date of achieving the first CR, CRi, nPR, or PR (PR or better) to the date of progressive disease (PD) or death due to any cause, whichever occurred first. The CR, CRi, nPR, and PR are defined in the above outcome measure. For CLL, PD is defined as any one of the criteria: lymphocytes \>=50% increase from baseline, appearance of any new lesion or new hepatomegaly or splenomegaly or \>= 50% increase in lymphadenopathy/hepatomegaly/splenomegaly, decrease of Hb levels \>2 g/dL or to \<10 g/dL, or decrease of platelets \>50% or to\<100,000/μL. For SLL, PD is defined as any one of the criteria: appearance of a new lesion \>1.5 cm in any axis; \>=50% increase in the products of at least 2 LNs; \>=50% increase in the longest diameter of a previously identified node \>1 cm in short axis; \>=50% increase in the size of the L and/or S or previously determined nodules in the L/S; or new or recurrent BM involvement. The DoR was estimated using Kaplan-Meier method.

The PFS is defined as the time from the date of first dose of study drug to the date of first PD or death due to any cause, whichever occurred first. For CLL, PD is defined as any one of the criteria as: lymphocytes \>=50% increase from baseline, appearance of any new lesion or new appearance of hepatomegaly or splenomegaly or \>= 50% increase in lymphadenopathy/hepatomegaly/splenomegaly, decrease of Hb levels \>2 g/dL or to \<10 g/dL, or decrease of platelets \>50% or to\<100,000/μL. For SLL, PD is defined as any one of the criteria as: appearance of a new lesion \>1.5 cm in any axis; \>=50% increase in the products of at least 2 LNs; \>=50% increase in the longest diameter of a previously identified node \>1 cm in short axis; \>=50% increase in the size of the L and/or S or previously determined nodules in the L/S; or new or recurrent BM involvement. The PFS was estimated using Kaplan-Meier method.

The TTNT is defined as the time from the date of first dose of study drug to the date of institution of subsequent anticancer therapy for CLL or death due to any cause, whichever occurred first. The TTNT was estimated using Kaplan-Meier method.

The OS is defined as the time from the date of first dose of study drug to death due to any cause or last follow-up. The OS was estimated using Kaplan-Meier method.

The time to initial PR or better response is defined as the time from the date of first dose of study drug to the date of first PR or better (ie, CRi or CR). For CLL, CR: lymphocytes (lympho) \<4×10\^9/L, normocellular bone marrow (BM) \<30% lympho, no B-lymphoid nodules, normal lymph nodes (NLN), liver and spleen (L/S), absolute neutrophils (ANC) \>1.5×10\^9/L, platelets \>100×10\^9/L, hemoglobin (Hb) \>11g/dL; CRi: lympho \<4×10\^9/L, hypocellular BM, NLN, L/S, persistent anemia/thrombocytopenia/neutropenia; PR: \>=50% reduction in lymphadenopathy and/or enlargement of L/S or lympho (\<5×10\^9/L or \>=50% decrease from baseline), criteria of ANC/platelets/Hb per CR or \>=50% improvement over baseline. Hematology without exogenous growth factors/transfusion. For SLL, CR: no disease/disease-related symptoms, normal/\<=1cm LN, no enlargement of L/S/NL, disease-free BM; PR: \>=50% decrease in dominant masses with no size increase/new lesions, and \>=50% reduction of nodules in S/L.

The time to initial CR is defined as the time from the date of first dose of study drug to the date of first CR. For CLL, CR: lymphocytes \< 4×10\^9/L, normocellular bone marrow \< 30% lymphocytes, no B-lymphoid nodules, normal lymph nodes, liver and spleen, absolute neutrophils \> 1.5×10\^9/L, platelets \> 100×10\^9/L, hemoglobin \> 11g/dL. Hematology without exogenous growth factors/ transfusion. For SLL, CR: no disease/disease-related symptoms, normal/\<=1 cm lymph nodes, no enlargement of liver/spleen/lymphoid nodules, disease-free bone marrow.

The Tmax of acalabrutinib and its metabolite ACP-5862 are reported.

The Cmax of acalabrutinib and ACP-5862 are reported.

The AUC0-last of acalabrutinib and ACE-5862 are reported.

The AUC0-inf of acalabrutinib and ACE-5862 are reported.

The λz of acalabrutinib and ACP-5862 are reported.

The t1/2 of acalabrutinib and ACP-5862 are reported.

The EORTC QLQ-C30 is a 30-item questionnaire designed to assess health related quality of life in cancer participants. It includes a 30-item questionnaire designed to assess health related quality of life in cancer patients. There are 9 multi-item scales: 5 functional scales (physical, role, cognitive, emotional, and social); 3 symptom scales (fatigue, pain, and nausea and vomiting); and a global health and quality-of-life scale. Several single-item symptom measures are also included (dyspnea, insomnia, appetite, constipation, diarrhea, and financial impact). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100. A high score for a functional scale represents a high (healthy/better) level of functioning, a high score for the global health status represents a high (better) quality of life, but a high score for a symptom scale represents a high (worse) level of symptoms/problems.

Acerta Pharma BV

Syndrome

Hodgkin Disease

Hodgkin Lymphoma

Acute Graft Versus Host Disease

Richter Syndrome

Anti-Infective Agents

Cytarabine

Fludarabine

Fludarabine phosphate

Oxaliplatin

Antimetabolites

Immunosuppressive Agents

Antiviral Agents

Starting dose oxaliplatin 17.5mg/m\^2/day intravenous (IV) for 4 days; Fludarabine 30 mg/m\^2 IV and Cytarabine 1 g/m\^2 IV for two days, + Rituximab 375 mg/m\^2 IV on Day 3, Cycle 1 then Day 1 following cycles.

1 g/m\^2 given IV for two days (Days 2 and 3).

30 mg/m\^2 given IV for two days (Days 2 and 3).

Starting dose of 17.5 mg/m\^2 IV for 4 days (Days 1 through 4).

375 mg/m\^2 IV on Day 3 of the first cycle over 4-6 hours and on Day 1 on every cycle following.

William G. Wierda, MD, PhD

Primary Objectives:

1. Determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of oxaliplatin in combination with fludarabine, Ara-C and rituximab in patients with Richter's transformation, prolymphocytic leukemia (PLL), or refractory/relapsed B-cell chronic lymphocytic leukemia (CLL).
2. Assess the complete response (CR) and partial response (PR) rate to combination therapy of oxaliplatin, fludarabine, Ara-C and rituximab in patients with Richter's transformation, PLL or refractory/relapsed B-cell CLL.
3. Determine the safety and toxicity profile of combination therapy of oxaliplatin, fludarabine, Ara-C and rituximab in patients with Richter's transformation, PLL or refractory/relapsed B-cell CLL.

Secondary Objectives:

1. Determine the duration of response, failure-free survival, and overall survival.
2. Determine the incidence of infections (bacterial, fungal, and viral) in patients with Richter's transformation, prolymphocytic leukemia or refractory/relapsed B-cell CLL treated with rituximab, oxaliplatin, fludarabine and Ara-C; monitor immune parameters such as T cell counts and immunoglobulin levels; and monitor Epstein-Barr virus (EBV) status.
3. Characterize the pharmacodynamics of oxaliplatin in leukemia cells with respect to total adduct formation, cross-link formation and excision deoxyribonucleic acid (DNA) responses. Compare these parameters in cells from the same patient after treatment with oxaliplatin in combination with fludarabine and Ara-C.

Oxaliplatin, fludarabine, cytarabine and rituximab are anticancer drugs. Oxaliplatin is a platinum compound that has been shown to be effective in fighting other cancers. Oxaliplatin is a third generation platinum compound with higher activity and less toxicity in colon cancer and other tumors compared to other platinum compounds, such as cisplatin. Oxaliplatin has shown activity in patients with relapsed or refractory non-Hodgkin's lymphoma.

Before treatment starts, you will have a complete physical exam and routine blood tests (about 2 teaspoons). A bone marrow sample will be collected. To collect a bone marrow sample, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large needle. Women who are able to have children must have a negative blood or urine pregnancy test.

This research study has two parts, a Phase I part and a Phase II part. You will receive at least 1 cycle of therapy.

Oxaliplatin will be given through a needle in your vein (called an IV) for 4 days (Days 1 through 4). Rituximab will be given through an IV on Day 3 of the first cycle and on Day 1 on every cycle after that. One day after the first dose of oxaliplatin and rituximab (Day 2), fludarabine and cytarabine will be given through an IV for two days (Days 2 and 3). Peg-filgrastim will be given subcutaneously (through a needle just under your skin) on Day 6. Other IV fluids such as saline will be given on all of the treatment days to keep you from being dehydrated, which means that the daily visit may take eight hours. The combination will be repeated once a cycle (every 28 days) for up to a total of 6 cycles.

During the Phase I and II phases of the study, researchers will be testing different dose levels of the study drug combination. Three patients will be enrolled at each dose level. Each time the dose level is raised, it will occur after each patient has been monitored for 28 days. Individual patients who do not experience serious drug-related side effects after the second cycle may receive the next higher dose level for the following treatment cycles.

Drugs will be given before each dose of rituximab to lower the risk of side effects. If side effects do occur during rituximab treatment, rituximab may have to be stopped until the side effects go away and then restarted. This may make your time in the outpatient area longer.

The first treatment cycle will be given at M. D. Anderson. Depending on your response to treatment, up to 5 more cycles can be performed either at M. D. Anderson or at home with your regular physician. After 3 cycles of treatment, you will be checked at M. D. Anderson to see if the disease is responding to treatment. If the disease is responding after 3 cycles of therapy, you may continue to receive therapy for up to 3 more cycles. If the disease is not responding, you will be taken off the study and your doctor will discuss other treatment options with you.

Once the best safe dose of the drug combination is found in the Phase I portion of the study, the next group of participants entering the study will take part in the Phase II portion of the study. The goal of this part of the study is to look at the effects of the drug combination in patients with refractory CLL, prolymphocytic leukemia or Richter's transformation. The dose level for the combination will be the one found in the Phase I part of the study.

The same dose levels for all four drugs will be used throughout the Phase II portion of the study, unless intolerable side effects occur. In that case, the dose may be lowered or the treatment may be stopped. You will be taken off study if the disease gets worse.

During each treatment cycle, you will have blood samples (about 1 teaspoon each) taken once every 1-2 weeks. Bone marrow biopsies will be done at the end of the 3rd and 6th chemotherapy cycles.

After your last cycle of treatment is completed, you will have blood drawn (about 2 teaspoons each) every 3 months for as long as you are in remission, for routine testing.

This is an investigational study. The FDA has authorized the use of these drugs for research only, when given for this purpose. All of these drugs are commercially available for other types of treatment. Oxaliplatin will be free of charge during the study. You and/or your insurance company will be responsible for the cost of the other drugs used in this study. Patients will be enrolled at M. D. Anderson, University of California, San Diego, or Dana-Farber Cancer Institute. Up to 52 patients will take part in this multicenter study. The estimated number of patients who will be treated at M. D. Anderson is up to 52.

Oxaliplatin, Fludarabine, Cytarabine and Rituximab in Richter's Syndrome, Refractory CLL and PLL

A Phase I-II Study of Oxaliplatin, Fludarabine, Cytarabine and Rituximab in Patients With Richter's Transformation, Prolymphocytic Leukemia or Refractory/Relapsed B-Cell Chronic Lymphocytic Leukemia

MTD defined as dose level at which 2/3 or 2/6 participants experience Dose Limiting Toxicity (DLT), where DLTs are any oxaliplatin-related ≥Grade 3 non-hematological toxicity involving a major organ system (brain, heart, kidney, liver, lung) in the National Cancer Institute (NCI) Version 3.0 toxicity scale.

According to International Workshop Response Criteria for Non-Hodgkin's Lymphomas: Complete remission (CR) defined as \> 30% lymphocytes in the bone marrow, recovery of blood counts and no clinical symptoms; and Partial remission (PR) defined as \> 50% decrease of clinical symptoms from baseline and recovery from blood counts.

Sanofi

M.D. Anderson Cancer Center

Oxaliplatin, Fludarabine, Cytarabine + Rituximab

Age Continuous

Sex: Female, Male

United States

Region of Enrollment

William Wierda, M.D./Associate Professor

Of the 48 study participants, 19 were enrolled in the Phase I MTD group and included in the MTD analysis.

Maximum Tolerated Dose (MTD) Oxaliplatin

Complete response (CR)

Partial response (PR)

Number of Participants With a Complete Response or Partial Response

Overall Study

Immunomodulating Agents

Immunotoxins

Immunotoxin HA22

Immunoconjugates

Immunotoxin therapy

CAT-8015 immunotoxin

Biological therapy

Marie Fuerst, RN, MS

Peter Rosen, MD

Mary Cangany, RN, CCRP

Larry Cripe, MD

NCI Clinical Trials Referral Office

Robert J Kreitman, MD

Krzysztof Jamoziak, MD

Tadeusz Robak, Professor

RATIONALE: The CAT-8015 immunotoxin can bind tumor cells and kill them without harming normal cells. This may be an effective treatment for chronic lymphocytic leukemia (CLL), prolymphocytic leukemia (PLL), or small lymphocytic lymphoma (SLL that has not responded to chemotherapy, surgery or radiation therapy.

PURPOSE: Phase I dose escalation study to determine the maximum tolerated dose of CAT-8015 immunotoxin in treating patients who have chronic lymphocytic leukemia, prolymphocytic leukemia or small lymphocytic lymphoma that has not responded to treatment

OUTLINE: Patients receive CAT-8015 IV over 30 minutes on days 1, 3, and 5 followed by rest. Treatment repeats every 4 weeks for up to a total of 10 courses in the absence of dose limiting toxicity, complete response or disease progression. Patients are followed at 1, 3, 6,12,15,18, 21, 24 months following the start of the last treatment cycle.

Cohorts of 3-6 patients each will receive escalating doses of recombinant CAT-8015 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose proceeding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, between16 to 25 new patients will be added to the MTD cohort depending on how well the CAT-8015 is tolerated.

Safety Study of CAT-8015 Immunotoxin in Patients With CLL, PLL or SLL With Advance Disease

A Phase 1, Multicenter, Dose Escalation Study of CAT-8015 in Patients With Relapse or Refractory Chronic Lymphocytic Leukemia (CLL), Prolymphocytic Leukemia (PLL), or Small Lymphocytic Lymphoma (SLL)

Cambridge Antibody Technology

Alemtuzumab

Group 3: 375 mg/m\^2 Rituximab + 30 mg SQ Alemtuzumab

375 mg/m\^2 by standard IV (intravenous) infusion on days 1, 8, 15, and 22 of weeks 1-4.

Dose escalation of 3, 10 and 30 mg subcutaneously (SQ) during week 1, followed by dose of 30 mg subcutaneously three times weekly (e.g. Monday-Wednesday - Friday) starting on week 2 for a total of 12 weeks (2-13).

Stefan Faderl, M.D.

The goal of this clinical research study is to find out how well Campath (alemtuzumab), Rituxan (rituximab), or a combination of the 2 drugs may control Chronic Lymphocytic Leukemia (CLL) that is left after chemotherapy. The safety of these drugs will also be studied.

Study Drugs:

Alemtuzumab and rituximab are both monoclonal antibodies. Monoclonal antibodies are proteins designed to attach to a protein on the surface of the leukemia cell. By attaching to the leukemia cell, monoclonal antibodies alert the immune system to target that cell and kill it.

Study Groups:

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the roll of a dice) to 1 of 3 groups. Group 1 will receive rituximab alone. Group 2 will receive alemtuzumab alone. Group 3 will receive both drugs together.

At the beginning of the study, the chance of being assigned into any of the groups is about equal. However, once enough participants are on study and the response rate in each group is known, you will have a slightly better chance of being assigned to the group with the highest response rate.

Study Drug Administration:

Group 1:

If you are in Group 1, rituximab will be given through a needle in your vein 1 time a week for 4 weeks. The first time you receive rituximab, it will be given over about 4-6 hours. Depending on any side effects you may have, the later infusions may be given over about 2-4 hours.

Before each dose of rituximab, you will receive drugs such as benadryl (diphenhydramine), Tylenol (acetaminophen), and sometimes steroids (either by mouth or into your vein) to try and prevent and/or help control side effects such as fevers and chills.

To help prevent infections, you will take the antibiotic valacyclovir (or a similar drug). Valacyclovir is taken 1 time a day every day. Your doctor will describe this to you in more detail.

Group 2:

If you are in Group 2, alemtuzumab will be given as an injection under your skin 3 times a week for 13 weeks. You will have to come to the clinic for each dose, learn how to inject it yourself, or have someone else taught how to inject you.

To help prevent infections, you will take the antibiotic trimethoprin/sulfamethoxazole (SMX). Your doctor will tell you if you will take the tablet 2 times a day either 3 times a week (Monday, Wednesday, and Friday) or 2 times a week (Saturday and Sunday). You will also take either the antibiotic valganciclovir or valacyclovir. Valganciclovir tablets are taken 2 times every day. Valacyclovir is taken 1 time a day every day. You will continue to take the antibiotics for at least 3 months after your last dose of alemtuzumab.

Group 3:

If you are in Group 3, rituximab will be given through a needle in your vein 1 time a week for 4 weeks. The first time you receive the rituximab, it will be given over about 4-6 hours. Depending on any side effects you may have, the later infusions may be given over about 2-4 hours.

Alemtuzumab will be given as an injection under your skin 3 times a week for 13 weeks. You will have to come to the clinic for each dose, learn how to inject it yourself, or have someone else taught how to inject you.

Before each dose of rituximab, you will receive drugs such as benadryl (diphenhydramine), Tylenol (acetaminophen), and sometimes steroids (either by mouth or into your vein) to try and prevent and/or help control side effects.

To help prevent infections, you will take the antibiotic trimethoprin/sulfamethoxazole (SMX). Your doctor will tell you if you will take the tablet 2 times a day either 3 times a week (Monday, Wednesday, and Friday) or 2 times a week (Saturday and Sunday). You will also take either the antibiotic valganciclovir or valacyclovir. Valganciclovir tablets are taken 2 times every day. Valacyclovir is taken 1 time a day every day. You will continue to take the antibiotics for at least 3 months after your last dose of alemtuzumab.

Study Visits:

Every week while you are receiving therapy, blood (about 1 tablespoon) will be drawn for routine tests.

Six (6), 12, and 18 weeks (+/- 1 week) after you begin receiving the study drug(s) and then every 6 months (+/- 1 month) after that, you will have bone marrow biopsies and/or aspirates to check the status of the disease and to check for residual disease.

Every 6 months (+/- 3 months) after you have stopped receiving therapy, you will have a physical exam and blood (about 1 tablespoon) will be drawn for routine tests.

If you are in Group 2 or 3, during Week 3 and 6, blood (about 1 teaspoon) will be drawn to check for the cytomegalovirus (CMV) infection. This infection may occur in people with weakened immune systems.

If your doctor thinks it is necessary, you will have a chest x-ray and/or other scans.

Length of Study:

If you are in Group 1, you will take the study drug for up to 4 weeks. If you are in Groups 2 or 3, you will take the study drug(s) for up to 13 weeks. You will be taken off treatment early if you have intolerable side effects.

You will remain on study as long as the disease does not get worse.

This is an investigational study. Rituximab is FDA approved and commercially available for non-Hodgkin's lymphoma. However, it is not approved for the treatment of CLL.

Alemtuzumab is FDA approved and commercially available. It has been approved for the treatment of CLL when given by vein. It has not been approved to be given as an injection under the skin or for treatment after chemotherapy.

Up to 100 patients will take part in this study. All will be enrolled at M. D. Anderson.

Alemtuzumab + Rituximab Consolidation in CLL

A Randomized Trial of Rituximab vs Alemtuzumab vs Alemtuzumab + Rituximab as Consolidation Therapy for Patients With Chronic Lymphocytic Leukemia (CLL) With Evidence of Residual Disease Following Prior Chemo(Immuno)Therapy

Molecular Remissions (minimal residual disease (MRD) flow cytometry-negative) after monoclonal antibody consolidation therapy. Molecular remission is defined as resolution of all detectable disease below the limits of the MRD flow cytometry assay sensitivity.

Progression-free survival (PFS) is measured from date of trial entry until documented progression of disease or death from any cause.

The definition of toxicities include any \>/= grade 3 non-hematologic toxicity, \>/= grade 3 infection, and any symptomatic (i.e. febrile) documented CMV (cytomegalovirus) reactivation, according to NCI-WG definitions.

Genzyme, a Sanofi Company

Group 1: 375 mg/m\^2 intravenous (IV) Rituximab Alone

Group 2: 30 mg subcutaneously (SQ) Alemtuzumab Alone

Rituximab + Alemtuzumab

Total

<=18 years

Between 18 and 65 years

>=65 years

Age, Categorical

Female

Male

Gender

Stefan Faderl, MD / Professor

No analysis available participant ineligible for evaluation; study terminated due to slow accrual.

Number of Patients With Molecular Remissions at 52 Weeks

Progression-free Survival

52 Week Toxicity Rate

Recurrence

Antibodies

Antibodies, Monoclonal

Lenalidomide

Immunoglobulins

Ibrutinib

Angiogenesis Inhibitors

Growth Inhibitors

Patients receive anti-CD19 monoclonal antibody MOR00208 IV over 2 hours on day 1 (days 1, 2, 8, 15, and 22 of course 1 only) and lenalidomide PO daily on days 1-28 (days 9-28 of course 1 only). Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Correlative studies will be collected for this trial and will focus on the effects of MOR00208 alone and in combination with lenalidomide on immune effector cell number and function.

Patients receive anti-CD19 monoclonal antibody MOR00208 IV over 2 hours on day 1 (days 1, 2, 8, 15, and 22 of course 1 only) and ibrutinib PO daily on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Correlative studies will be collected for this trial and will focus on the effects of MOR00208 alone and in combination with ibrutinib on immune effector cell number and function.

MOR00208

lenalidomide

Correlative studies associated with this trial will focus on the effects of MOR00208 alone and in combination with lenalidomide on immune effector cell number and function.

Correlative Studies

Jennifer Woyach, MD

This phase II trial studies how well anti-cluster of differentiation (CD)19 monoclonal antibody MOR00208 and lenalidomide work in treating patients with relapsed, refractory, or previously untreated chronic lymphocytic leukemia, small lymphocytic lymphoma, or prolymphocytic leukemia. Monoclonal antibodies, such as anti-CD19 monoclonal antibody MOR00208, can block cancer growth in different ways. Some block the ability of cancer to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Giving anti-CD19 monoclonal antibody MOR00208 and lenalidomide may kill more cancer cells.

PRIMARY OBJECTIVES:

I. To determine the overall response rate (ORR) at 6 months for patients with relapsed or refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL)/prolymphocytic leukemia (PLL) treated with the combination of MOR00208 plus lenalidomide.

II. To determine the overall response rate (ORR) at 6 months for patients with treatment-naive CLL/SLL/PLL treated with the combination of MOR00208 plus lenalidomide.

III.To obtain preliminary data on toxicity profiles and efficacy with the combination of MOR00208 plus lenalidomide in patients with Richter's Transformation IV. To obtain preliminary data on efficacy of MOR00208 in patients with progressive disease on ibrutinib monotherapy

SECONDARY OBJECTIVES:

I. To determine the overall response rate (ORR) at 12 months for patients with untreated CLL/SLL/PLL or relapsed/refractory disease treated with the combination of MOR00208 plus lenalidomide.

II. To determine the complete response (CR) rate, nodular partial response (nPR) rate, partial response (PR) rate, and stable disease (SD) rate for patients with untreated CLL/SLL/PLL or relapsed or refractory disease treated with the combination of MOR00208 plus lenalidomide.

III. To summarize the progression free survival (PFS), time to next treatment, and overall survival (OS) for each of two cohorts of patients treated with this regimen.

IV. To evaluate toxicity with this regimen, including frequency and severity of toxicities, dose reduction requirements, and adverse events requiring drug discontinuation.

V. To perform baseline analysis of patients enrolled on this trial including fluorescence in situ hybridization (FISH), stimulated karyotype, zeta-chain-associated protein kinase 70 (Zap-70) methylation, and immunoglobulin variable region heavy chain (IgVH) mutational status and describe relationships between these biomarkers and ORR or PFS for each of two cohorts with this regimen.

VI. To determine the effect of this regimen on total immunoglobulins, CD4+ and CD8+ T cells, natural killer (NK) cells, and interleukin-21 receptor (IL-21R) expression on CLL cells.

VII. To determine whether NK cells and T cells are activated in response to MOR00208 alone or in combination with lenalidomide.

VIII. To estimate the rate of minimal residual disease (MRD) in patients achieving CR, and whether this correlates with PFS.

OUTLINE:

Patients receive anti-CD19 monoclonal antibody MOR00208 intravenously (IV) over 2 hours on day 1 (days 1, 2, 8, 15, and 22 of course 1) and lenalidomide orally (PO) daily on days 1-28 (days 9-28 of course 1). Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Phase II MOR00208 in Combination With Lenalidomide for Patients With Relapsed or Refractory CLL, SLL or PLL or Older Patients With Untreated CLL, SLL or PLL

A Phase II Study of MOR00208 in Combination With Lenalidomide for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia(CLL)/Small Lymphocytic Lymphoma (SLL)/Prolymphocytic Leukemia (PLL), Including Those Who Have Relapsed on Ibrutinib, or Patients With Untreated CLL/SLL/PLL and an Open Pilot Study for Patients With Richters Transformation (RT)

Within each cohort, the proportion of patients who achieve an overall response will be estimated by the sum of the number of complete responses, complete responses with incomplete recovery, nodular partial responses, and partial responses divided by the total number of evaluable patients. Ninety percent exact binomial confidence intervals for the true overall response rate will be calculated for those patients included to evaluate the decision criteria.

The ORR with 90% exact binomial confidence intervals will be calculated. The degree of response for evaluable patients will also be summarized. In addition, the number of patients who achieve CR but remain positive for MRD will be documented.

PFS will be summarized with simple descriptive statistics obtained using the Kaplan-Meier method.

Time to next treatment will be summarized with simple descriptive statistics obtained using the Kaplan-Meier method.

OS will be summarized with simple descriptive statistics obtained using the Kaplan-Meier method.

Relationships between FISH variables and ORR or PFS will be explored graphically (e.g. side-by-side boxplots or Kaplan-Meier plots), where estimates with confidence intervals will be presented as the primary method of analysis due to the limited number of patients.

Relationships between stimulated karyotype variables and ORR or PFS will be explored graphically (e.g. side-by-side boxplots or Kaplan-Meier plots), where estimates with confidence intervals will be presented as the primary method of analysis due to the limited number of patients.

Relationships between Zap-70 variables and ORR or PFS will be explored graphically (e.g. side-by-side boxplots or Kaplan-Meier plots), where estimates with confidence intervals will be presented as the primary method of analysis due to the limited number of patients.

Relationships between IgVH variables and ORR or PFS will be explored graphically (e.g. side-by-side boxplots or Kaplan-Meier plots), where estimates with confidence intervals will be presented as the primary method of analysis due to the limited number of patients.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase I and II Study of Auranofin in Chronic Lymphocytic Leukemia (CLL)	NCT01419691	Chronic Lymphoc... Small Lymphocyt... Leukemia, Proly...	auranofin	18 Years -	University of Kansas Medical Center
Acalabrutinib in Combination With Anti-CD20 and Venetoclax in Relapsed/Refractory or Untreated CLL/SLL/PLL	NCT02296918	Chronic Lymphoc... Small Lymphocyt... Prolymphocytic ...	acalabrutinib Obinutuzumab Venetoclax Rituximab	-	Acerta Pharma BV
Oxaliplatin, Fludarabine, Cytarabine and Rituximab in Richter's Syndrome, Refractory CLL and PLL	NCT00452374	Leukemia	Cytarabine Fludarabine Oxaliplatin Rituximab	18 Years -	M.D. Anderson Cancer Center
Safety Study of CAT-8015 Immunotoxin in Patients With CLL, PLL or SLL With Advance Disease	NCT00457860	Leukemia	Immunotoxin the... CAT-8015 immuno... Biological ther...	18 Years -	Cambridge Antibody Technology
Acalabrutinib in Combination With Anti-CD20 and Venetoclax in Relapsed/Refractory or Untreated CLL/SLL/PLL	NCT02296918	Chronic Lymphoc... Small Lymphocyt... Prolymphocytic ...	acalabrutinib Obinutuzumab Venetoclax Rituximab	-	Acerta Pharma BV
Alemtuzumab + Rituximab Consolidation in CLL	NCT00771602	Chronic Lymphoc... Leukemia	Rituximab Alemtuzumab	18 Years -	M.D. Anderson Cancer Center
Phase II MOR00208 in Combination With Lenalidomide for Patients With Relapsed or Refractory CLL, SLL or PLL or Older Patients With Untreated CLL, SLL or PLL	NCT02005289	Contiguous Stag... Noncontiguous S... Prolymphocytic ... Recurrent Small... Refractory Chro... Stage I Chronic... Stage I Small L... Stage II Chroni... Stage III Chron... Stage III Small... Stage IV Chroni... Stage IV Small ...	MOR00208 lenalidomide Correlative Stu...	18 Years - 80 Years	Ohio State University Comprehensive Cancer Center
Phase II MOR00208 in Combination With Lenalidomide for Patients With Relapsed or Refractory CLL, SLL or PLL or Older Patients With Untreated CLL, SLL or PLL	NCT02005289	Contiguous Stag... Noncontiguous S... Prolymphocytic ... Recurrent Small... Refractory Chro... Stage I Chronic... Stage I Small L... Stage II Chroni... Stage III Chron... Stage III Small... Stage IV Chroni... Stage IV Small ...	MOR00208 lenalidomide Correlative Stu...	18 Years - 80 Years	Ohio State University Comprehensive Cancer Center

Spots Global Cancer Trial Database for pll

Every month we try and update this database with for pll cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for pll

Every month we try and update this database with for pll cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for pll cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.