Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Hematologic Neoplasms

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

All Drugs and Chemicals

Dexamethasone

Dexamethasone acetate

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

CB-5083 will be administered orally, 4 days on and 3 days off, for 28 day cycles, as a single agent to subjects with lymphoid hematological malignancies

CB-5083 will be administered orally, 4 days on and 3 days off, for 28 day cycles, as a single agent to subjects with relapsed and refractory multiple myeloma; in addition, subjects who develop progressive disease at the end of Cycle 1, or beyond, may receive their current dose of CB-5083 in combination with oral or IV low dose Dexamethasone (40 mg)

CB-5083 will be administered orally, daily, 4 days on and 3 days off, for 28 day cycles, as a single agent to subjects with diffuse large B-cell lymphoma (DLBCL) or Waldenstrom Macroglobulinemia, if such arm is opened, per Sponsor

CB-5083

The purpose of this study is to determine the safety, tolerability, dose limiting toxicities, and maximum tolerated dose of CB-5083 in subjects with lymphoid hematological malignancies.

A Phase 1 Study Evaluating CB-5083 in Subjects With Lymphoid Hematological Malignancies

A Phase 1, Dose-Escalation/Dose-Expansion Study Evaluating the Safety, Pharmacokinetics and Pharmacodynamic Effects of Orally Administered CB-5083 in Subjects With Lymphoid Hematological Malignancies

Cleave Biosciences, Inc.

Antirheumatic Agents

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Cytoxan, Fludarabine, Total Body Irradiation (TBI), Cord Blood Stem Cell Infusion

50 mg/kg/dose will be given IV on day -5,-4, -3, -2 over 1 hour. The total dose to be given over 4 days is 200 mg/kg.

Cytoxan

40mg/m2/day will be given IV over 1 hour on day -4, -3, -2

1.75Gy/fraction will be given on day -9, -8, -7, -6

Total Body Irradiation (TBI)

The cord blood stem cells will be infused on day 0

Cord Blood Stem Cell Infusion

Caridad A Martinez, MD

Robert A Krance, MD

The purpose of this study is to determine the safety and effectiveness of UCBT to treat patients with lymphoid hematological diseases and to see if this treatment can decrease the incidence of leukemia relapse, GVHD and infections.

These patients have a type of blood cell disorder that is very hard to cure. This treatment that is being used in this trial is known as a stem cell transplant. This treatment might help the patient live longer without the disease. It uses much stronger doses of drugs and radiation to kill the diseased cells that could be given without the transplant. We also think that the healthy cells from the donor may help fight any diseased cells left after the transplant.

For the transplant to take place, we will administer stem cells from a 'donor' whose cells best 'match' the patient's. In this study umbilical cords will be the source of the stem cells. Before the transplant, two very strong drugs plus total body irradiation will be given to as preconditioning. This treatment will kill most of your blood-forming cells in the bone marrow. The patient will then get then healthy stem cells.

If the patient has the disease in the central nervous system (CNS), they will receive radiation to the head and spine before starting the conditioning. This is to try to get disease control in the CNS. Radiation will not be given for children under 2 yrs old.

Currently, many umbilical cord blood units are available in public banks for transplantation in patients lacking bone marrow donors. UCB transplants (UCBT) may offer several advantages over adult bone marrow or peripheral blood stem cell transplants, including:

1. rapid availability,
2. absence of donor risk,
3. low risk of transmissible infectious diseases,
4. low risk of acute GvHD (Graft vs. Host Disease)

The three main causes of death after umbilical cord blood transplantation for these kind of disorders are graft failure, infection and disease relapse.

In this study we are trying to address these three problems:

To help improve engraftment we will add the drug Fludarabine to Cytoxan and total body irradiation. Fludarabine is a very strong medicine. We will try to decrease infections and reduce leukemia relapse by using fludarabine instead of antithymocyte globulin (ATG).

After the eligible criterion for treatment has been met and a suitable UCB stem donor has been found, the patient will have a central line placed.

Research Therapy:

After placement of the central line, the following chemotherapy will be given to after admission to the hospital and before the infusion of the umbilical cord blood stem cells:

* 9 - 6 days before the infusion: Total Body Irradiation (TBI) in two fractions ("doses") per days.
* 5 - 2 days before the infusion: Cytoxan given daily for 4 days, over 1 hour as an intravenous infusion. Mesna will be given per standards. Mesna is a drug given to decrease the side effects of Cytoxan. It will be given daily as an intravenous infusion while the patient receives the Cytoxan.
* 4 - 2 days before the infusion: Fludarabine given daily for 3 days over 1 hour as an intravenous infusion.

Stem cell transplant (intravenous infusion of the UCB stem cells) - defined as day 0 of the treatment. All other "numbered" days relate to this infusion date. For example, Day 1 is the first day after the stem cell transplant.

The following medications will be given to help decrease side effects from the chemotherapy and UCB infusion: Cyclosporine A (CSA) will be given starting 3 days prior to the stem cell infusion. It will be given daily over 2 hours every 12 hours, after the infusion and then tapered if no GVHD is present.

Administration of Mycophenolate mofetil (MMF) will start on the day the stem cell infusion is completed and will continue daily for 45 days, unless the patient develops GvHD.

Intravenous immunoglobulin's (IVIG) will be given monthly until GVHD therapy is stopped and there is evidence that the patient's body is producing antibodies.

Study Evaluations: Various study evaluations will be performed before and during the trial.

Follow Up: After year 1, the patient will be asked to return to the clinic once a year for consultations and bone marrow tests. A follow up bone marrow biopsy and aspirate will be done 1 and 2 years after transplant. Consultations with specialists will be similar to the ones the patient had before the transplant.

Umbilical Cord Blood Transplant for Children With Lymphoid Hematological Malignancies

Umbilical Cord Blood Transplant for Children With Lymphoid Hematological Malignancies (UCALL)

To determine the survival rate at 1 year after umbilical cord blood transplant in pediatric patients with lymphoid hematological malignancies

To assess platelet recovery at day 42 post transplant

To estimate the risk of severe grade III-IV acute GvHD at day 100.

To estimate the risk of chronic GvHD at 1 year

To assess relapse rate at 1 and 3 years after transplant.

To assess neutrophil count recovery at day 42 post transplant

To evaluate T/B/NK cell recovery and function at day 100, 6, 12, and 24 months after transplant.

To assess leukemia free survival at 1 and 3 years.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Phase 1 Study Evaluating CB-5083 in Subjects With Lymphoid Hematological Malignancies	NCT02223598	Lymphoid Hemato... Relapsed and Re...	CB-5083 Dexamethasone	18 Years -	Cleave Biosciences, Inc.
Umbilical Cord Blood Transplant for Children With Lymphoid Hematological Malignancies	NCT01247688	Lymphoid Hemato... Umbilical Cord ...	Cytoxan Fludarabine Total Body Irra... Cord Blood Stem...	-	Baylor College of Medicine

Spots Global Cancer Trial Database for lymphoid hematological malignancies