Clofarabine and Non-Myeloablative Allogeneic Hematopoietic Transplantation

NCT00626626 | Terminated Phase 1 Results DMC

• 1 other identifier: 25223
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

Allogeneic hematopoietic transplant is curative for many patients with hematological neoplasms but conditions to provide optimal engraftment and anti-tumor efficacy with minimal toxicity are still under way. Clofarabine is a newly licensed agent with dramatic anti-leukemic activity. Its incorporation into a regimen for pre-transplant conditioning of acute leukemia and lymphoma patients is logical, exploiting both the anti-tumor activities it is recognized to have and the immunosuppressive activity seen with drugs in its class.

Conditions

Leukemia; Myelodysplastic Syndrome; Chronic Myelogenous Leukemia; Lymphoma; Hodgkin's Lymphoma; Multiple Myeloma

Keywords

leukemia; myelodysplastic syndrome; chronic myelogenous leukemia; lymphoma; mantle cell lymphoma

Outcome Measures

Primary Outcomes (1)

• Engraftment of Allogeneic Blood Cells.

  Establish the safety of Clofarabine and cyclophosphamide preceding allogeneic hematopoietic engraftment. Assess the efficacy of Clofarabine and cyclophosphamide as conditioning for promoting allogeneic hematopoietic engraftment. Adequacy of engraftment will be assessed via assessment of chimerism (percent donor engraftment). Less than 20% engraftment by day 30 is then failure of engraftment. Safety is defined per common toxicity criteria - Non-Hematological and non renal toxicities of ≥grade 3 or ≥grade 4 up to day 30 are scored as toxicity.

  two years

Secondary Outcomes (2)

• Disease-Free Survival

  Two years

• Overall Survival

  2 years

Study Arms (2)

"Clofar, Cyclophos, Alemtuzumab"

EXPERIMENTAL

Phase 1: 1-3 patients will be treated in order to establish Cyclophosphamide and Clofarabine dose and to confirm reasonable safety and engraftment efficacy. Drug - Clofarabine,Cyclophosphamide \& Alemtuzumab - Clofar (30mg/m2) D -8 to -4; Cyclo (500mg/m2) D -8 \& -7 \& Alem (20mg over 2hrs)

Drug: Clofar, Cyclophos, Alemtuzumab

"Clofar, Cyclophos,Alemtuzumab(Ph II)"

EXPERIMENTAL

Phase II patients 4-9 will treat at the selected dose level of Clofarabine and Cyclophosphamide. Drug - Clofarabine, Cyclophosphamide \& Alemtuzumab Clofar (30mg/m2) D -8 to -4; Cyclo (1000mg/m2) D -8 \& -7 \& Alem (20mg)-pts.

Drug: Clofar, Cyclophos,Alemtuzumab(Ph II)

Interventions

Clofar, Cyclophos, Alemtuzumab DRUG

Hydrocortisone 100 mg IV 30 minutes prior to each dose of Clofarabine. Ondansetron 16 mg PO or IV or another comparable antiemetic should be given prior to each dose of Clofarabine. An additional similar dose should be given prior to Cyclophosphamide dose. Clofarabine 30 mg/M2 -8 through - 4 (5 doses) infusion. Alemtuzumab on day -8 only and after Clofarabine. Cyclophosphamide 500 mg/m2 Days -8 and -7 (2 doses) given over 1 hour beginning 4 hours after the beginning of Clofarabine infusion.

Also known as: CLOLAR

"Clofar, Cyclophos, Alemtuzumab"

Clofar, Cyclophos,Alemtuzumab(Ph II) DRUG

Hydrocortisone 100 mg IV 30 minutes prior to each dose of Clofarabine. Ondansetron 16 mg PO or IV or another comparable antiemetic should be given prior to each dose of Clofarabine. An additional similar dose should be given prior to Cyclophosphamide dose. Clofarabine 30 mg/M2 -8 through - 4 (5 doses) infusion. Alemtuzumab on day -8 only and after Clofarabine. Cyclophosphamide 1000 mg/m2 Days -8 and -7 (2 doses) given over 1 hour beginning 4 hours after the beginning of Clofarabine infusion (patients 4-9)

Also known as: Clolar, Campath

"Clofar, Cyclophos,Alemtuzumab(Ph II)"

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Phase I
• Acute leukemia - secondary or beyond first remission or in CR with poor risk cytogenetics, myelodysplastic syndrome IPPS Int-2 or high risk, chronic myelogenous leukemia in accelerated or blast crisis and imatinib refractory or lymphoma having failed second line therapy or relapsed mantle cell lymphoma.
• Phase II
• Acute leukemia secondary or at high risk for relapse, myelodysplastic syndrome IPPS Int-2 or high risk or having failed other therapy, chronic myelogenous leukemia, lymphoma having failed first line therapy or at high risk, relapsed Hodgkin's, CCL progressed beyond initial therapy, multiple myeloma beyond initial response or with high risk features.
• Must have an HLA matched or 5/6 matched related donor at at least a 5/6 matched unrelated donor available.
• Have adequate renal and hepatic functions
• Capable of understanding the investigational nature, potential risk and benefits of the study and able to provide valid informed consent.
• Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment.
• Male and female patients of childbearing potential must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment.

You may not qualify if:

• Current concomitant chemotherapy, radiation therapy or immunotherapy other than as specified in the protocol.
• Use of investigational agents within 30 days and no cytotoxic anticancer agents within 2 weeks before study entry with the exception of hydroxyurea. The patient must have recovered from all non-hematological acute toxicities from any previous therapy.
• Other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver or other organ system that may place the patient at undue risk to undergo treatment.
• Patients with systemic fungal, bacterial, viral, or other infection not controlled.
• Pregnant or lactating patients.
• Any significant concurrent disease, illness or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow-up or interpretation of study results.
• Age \> 70 (for Phase 1) or 75 (for Phase 2)

Sponsors & Collaborators

• Milton S. Hershey Medical Center: lead

Study Sites (1)

Penn State College of Medicine, Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Related Publications (1)

• Karch J, Zhu J, Ehmann WC, Claxton D. Clofarabine and CY do not yield reliable engraftment of hematopoietic stem cells. Bone Marrow Transplant. 2012 Aug;47(8):1134-5. doi: 10.1038/bmt.2011.224. Epub 2011 Nov 14. No abstract available.

  PMID: 22080968 RESULT

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lymphoma; Hodgkin Disease; Multiple Myeloma; Lymphoma, Mantle-Cell

Interventions

sodium tetrametaphosphate; Alemtuzumab; Clofarabine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Leukemia, Myeloid; Myeloproliferative Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Lymphoma, Non-Hodgkin

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides

Results Point of Contact

• Title: Dr David Claxton
• Organization: Penn State Hershey Medical Center

dclaxton@hmc.psu.edu

717-531-8401

Study Officials

• David F Claxton, MD

  Penn State College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: February 20, 2008
• First Posted: February 29, 2008
• Study Start: May 1, 2007
• Primary Completion: January 1, 2010
• Study Completion: January 1, 2010
• Last Updated: April 25, 2018
• Results First Posted: April 25, 2018

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)